Design, Synthesis and Antibacterial Activity of Novel Pyrimidine-Containing 4H-Chromen-4-one Derivatives

Design, Synthesis and Antibacterial Activity of Novel Pyrimidine-Containing 4H-Chromen-4-one Derivatives | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Design, Synthesis and Antibacterial Activity of Novel Pyrimidine-Containing 4H-Chromen-4-one Derivatives Shijun Su, Mei Chen, Xuemei Tang, Feng Peng, Tingting Liu, Qing Zhou, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-92183/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract A series of pyrimidine-containing 4 H -chromen-4-one derivatives were designed and synthesized by combining bioactive substructures. All compounds were characterized using 1 H NMR, 13 C NMR, 19 F NMR and HRMS. Preliminary biological activity results showed that most of title compounds displayed significant inhibitory activity against Xanthomonas axonopodis pv. Citri ( Xac ), Xanthomonas oryzae pv. oryzae ( Xoo ) and Ralstonia solanacearum ( Rs ). In particular, compound 4c demonstrated a good inhibitory effect against Xac and Xoo , with half-maximal effective concentration(EC 50 ) values of 15.5 and 14.9 μg/mL respectively, and that of compound 4h showed the best antibacterial activity against Rs with an EC 50 value of 14.7 μg/mL, These results were better than both bismerthiazol (BT, 51.7, 70.1 and 52.7 μg/mL, respectively) and thiodiazole copper (TC, 77.9, 95.8 and 72.1 μg/mL respectively). In vivo antibacterial activity results indicated that compound 4c displayed better curative(42.4%) and protective (49.2%) activities for reducing rice bacterial leaf blight than both BT (35.2, 39.1%) and TC (30.8, 27.3%). The mechanism of compound 4c against Xoo was analysed through scanning electron microscopy (SEM). Results showed that the compound destroied the bacterial cell membrane structure. These results indicated that pyrimidine-containing 4 H -chromen-4-one derivatives are valuable in the research of new agrochemicals. Organic Chemistry 4H-Chromen-4-one derivatives pyrimidine antibacterial activity scanning electron microscopy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Background One of the main causes of plant diseases is bacterial infection, which causes a large amount of losses to the yield of economic crops every year. Such as, the citrus canker, tobacco bacterial wilt and rice bacterial leaf blight were caused by Xanthomonas axonopodis pv. citri ( Xac ), Ralstonia solanacearum ( Rs ) and Xanthomonas oryzae pv. oryzae ( Xoo ), respectively [ 1 – 3 ]. It was very serious and hard to manage effectively in agricultural production. Therefore, to protect crops from bacterial infection, the agrochemical (bismerthiazol, thiodiazole-copper and azoxy strobin) were used to prevent bacterial infection [ 4 , 5 ], but prolonged and abuse of traditional chemical pesticides not only enhances the resistance of the bacterial but also harmful to the environment and human health [ 6 – 8 ]. So, exploring novel highly-efficient, broad-spectrum and environmentally benign antibacterial agents is still an arduous task in pesticide science. 3,5,7-Trihydroxy-2-(3,4,5-trihydroxyphen-yl)-4 H -chromen-4-one (called "myricetin") (Fig. 1 A) belongs to a class of natural product that widely found in fruits, vegetables, and herbs, which has attracted more and more researchers due to the unique chemical structure and diverse biological activities [ 9 ]. Pharmacological research shows that myricetin and its derivatives present antiviral [ 10 , 11 ], antibacterial [ 12 – 14 ], antioxidation [ 15 , 16 ], anticancer [ 17 – 19 ], anti-inflammatory [ 20 ] and other biological properties, but most of them are limited to the field of medicine and have few applications in agriculture. In previous work, myricetin was took as the lead compound and active fragments were introduced, a mass of myricetin derivatives with significant biological activity have been discovered. In 2017, Zhong described myricetin derivatives containing 1,3,4 thiadiazole structure, which displaied good inhibitory effect on phytopathogenic bacteria [ 21 ]. Recently, Jiang reported a series of dithiocarbamate-containing 4 H -chromen-4-one derivatives with good in vitro antibacterial activity against Xac and Xoo , with an EC 50 values are 0.11 µg/mL and 1.58 µg/mL, respectively, which were far better than commercial agents bismerthiazol and thiodiazole copper [ 22 ]. Pyrimidine is an important class of heterocyclic compounds with wide applications in medicine and pesticides research due to their remarkable biological and pharmacological properties, such as antibacterial [ 23 – 25 ], antiviral [ 26 , 27 ], insecticide [ 28 , 29 ], anticancer [ 30 , 31 ], antimalaria[ 32 ], herbicida [ 33 ] and other biological activities[ 34 ]. In 2019, Zhang reported a series of derivatives containing pyrimidine ethers were synthesized, which have a good control effect on cucumber downy mildew [ 35 ]. Recently, Bai described some pyrimidine derivatives with signifcantly inhibitory effciencies against Gram-positive bacteria, Gram-negative bacteria and the fungus Candida albicans [ 36 ]. To develop novel, highly efficient and environment friendly bactericides, we introduced the pyrimidine moiety into 4 H -chromen-4-one, and a variety of pyrimidine-containing 4 H -chromen-4- one derivatives were synthesized and their antibactiral activity were evaluated. Results And Discussion Chemistry The structure of title compounds 4a-4x were characterized by 1 H NMR, 13 C NMR, 19 F NMR and HRMS. In 1 H NMR spectra, multiplet signals at δ 8.00–6.50 ppm show the presence of protons in aromatic nucleuses, and a singlet at δ 4.00-3.70 ppm reveals the presence of -OCH 3 group, the -O-CH 2 - and -S-CH 2 - characteristic groups between the 4 H -chromen-4-one skeleton and the substituted pyrimidine were observed at 4.10–3.37 ppm. The chemical shifts at 172.57–160.77 ppm 109.12–106.14 ppm, 27.80–32.12 ppm in the 13 C NMR spectra confirmed the existence of C = O, -CN and -CH 2 - groups, respectively. The HRMS spectra of title compounds show absorption signals of [M + H] + ions that is consistent with their molecular weight. X-ray crystal structure of title compounds 4 g To further confirm the structures of title compounds, compound 4 g was successfully cultured a single crystal and studied by single-crystal X-ray analysis as a representative example. The tested single crystal was crystallized from DMSO and acetone mixture solution containing compound 4 g . As shown in Fig. 3 B, C00T-H…O007 and O00R…H-C00R are two important intramolecular hydrogen bonds that combine with 4 H -chromen-4-one and pyrimidine heterocycle fragments to construct the main molecular scaffold of target compound 4 g . Besides, as presented in Fig. 3 C, four intermolecular hydrogen bonds (O008…H–C011, C00J…H-C00L, C00J…C00L-H, C011–H…O008) between neighboring molecules are primary forces for establishing the three-dimensional structure of target compound 4 g . crystallographic data listed in Table 1 . The deposition number is CCDC 2022970. Table 1 Crystal data of title compound 4 g. Crystal Data C 34 H 30 BrN 3 O 9 S Colourless/ block Mr = 736.57 ρ = 1.430 triclinic / P-1 Z = 2 a = 12.025(3) [Å] α = 103.276(15) [°] b = 12.509(4 ) [Å] β = 112.727(15) [°] c = 14.791(4) [Å] γ = 102.837(17) [°] F(000) = 832 V = 1873.79(9) [Å 3 ] Data Collection T min =0.310 T max =0.752 Absorption coefficient: 2.537 [mm-1] 3580 Independent reflections θ min = 3.870°, θ max = 64.332° 18889 Reflections collected -13 < = h<=13, -14 < = k<=14, -17 < = l 2r(I)] R1 = 0.0835, wR2 = 2591 Δρ max = 0.426 eÅ −3 , Δρ min = -0.750 eÅ −3 Antibacterial activity of the title compounds against Xac,Xoo and Rs in vitro The in vitro antibacterial activities of title compounds 4a - 4x against Xac , Xoo and Rs were determined using turbidimeter tests [ 37 , 38 ]. and the bismerthiazol, thiadiazole copper, and myricetin were tested as the control. Preliminary bioassays results in Table 2 indicated that Some compounds with good antibacterial activity against Xac , Xoo and Rs , Among them, compounds 4b , 4c , 4 h and 4o against Xac at 100 and 50 µg/mL with the inhibition rates of 80.4 and 51.4%, 91.3 and 69.0%, 85.3 and 51.4%, 83.2 and 50.5%, respectively, which were better than that of BT (64.6 and 43.4%), TC(55.0 and 34.6%) and myricetin(44.9 and 27.5%). The inhibitory rates of compounds 4c , 4 h , 4n and 4p indicated against Xoo at 100 µg/mL were 89.7, 81.2, 78.3 and 80.7%, respectively, which were superior to that of BT (63.9%), TC (49.5%) and myricetin (44.0%). Note that the inhibition rates of 4c , 4d , 4 h , 4n , 4o, 4p and 4x against Xoo at 50 µg/mL were 72.1, 41.7, 56.0, 54.7, 49.5, 56.0 and 45.6%, respectively, which were superior to those of bismerthiazol (44.5%), thiadiazole copper (36.5%) and myricetin (33.3%). Furthermore, 4c , 4d , 4 h , 4 k 4 l , 4o and 4w have fine antibacterial activity against Rs at 100 µg/mL with the inhibition rates of 90.9, 83.9, 92.7, 88.7, 83.2, 90.4 and 80.6%, which were better than those of BT (71.7%), TC (60.1%) and myricetin (50.7%). Similarly, the percentage inhibition of 4c , 4 h , 4 k , 4o and 4w against Rs at 50 µg/mL were 72.5, 76.2, 66.3, 71.9 and 59.0%, which exceeded BT (52.4%), TC (41.3%) and myricetin (29.6%). Table 2 Antibacterial activities of title compounds (4a-4x) against Xac, Xoo and Rs in vitro Compd. R n Xac (%) Xoo (%) Rs (%) 100 µg/mL 50 µg/mL 100 µg/mL 50 µg/mL 100 µg/mL 50 µg/mL 4a Ph 3 37.9 ± 2.8 25.6 ± 1.8 26.3 ± 1.6 13.6 ± 2.0 50.5 ± 0.6 39.2 ± 2.2 4b 3-CH 3 -Ph 3 80.4 ± 0.3 51.4 ± 0.9 20.7 ± 2.4 13.1 ± 4.2 46.9 ± 1.6 32.1 ± 2.1 4c 4-CH 3 -Ph 3 91.3 ± 0.6 69.0 ± 1.4 89.7 ± 0.9 72.1 ± 1.8 90.9 ± 1.7 72.6 ± 2.2 4d 4-OCH 3 -Ph 3 76.7 ± 3.5 40.9 ± 1.6 75.1 ± 0.8 41.70 ± 2.4 83.9 ± 1.4 51.2 ± 0.3 4e 3-Cl-Ph 3 28.7 ± 4.2 20.4 ± 2.6 50.3 ± 3.7 24.7 ± 3.0 34.3 ± 4.2 24.5 ± 1.6 4f 4-Cl-Ph 3 39.6 ± 2.9 28.9 ± 2.0 29.8 ± 1.8 18.1 ± 3.7 35.2 ± 3.6 27.9 ± 1.2 4 g 4-Br-Ph 3 25.3 ± 3.3 16.7 ± 3.1 31.2 ± 3.9 22.1 ± 5.4 67.0 ± 0.9 40.8 ± 1.2 4 h 3-F-Ph 3 85.3 ± 0.7 51.4 ± 2.0 81.3 ± 0.6 56.0 ± 2.2 92.8 ± 0.6 76.3 ± 1.2 4i 4-F-Ph 3 26.4 ± 2.0 25.6 ± 1.0 26.6 ± 2.1 12.5 ± 0.7 37.4 ± 5.6 19.7 ± 4.0 4j thiophen-2-yl 3 73.5 ± 0.8 41.9 ± 1.6 45.2 ± 2.1 21.8 ± 5.6 51.2 ± 1.1 30.2 ± 1.3 4 k furan-2-yl 3 31.5 ± 2.7 24.2 ± 1.7 32.8 ± 1.9 21.5 ± 1.6 88.7 ± 1.4 66.4 ± 0.31 4 l pyridin-4-yl 3 32.2 ± 1.7 21.96 ± 5.1 58.9 ± 1.7 32.5 ± 3.1 83.2 ± 1.6 50.9 ± 2.3 4 m Ph 4 47.1 ± 3.2 26.4 ± 2.2 47.7 ± 1.1 28.7 ± 1.9 51.8 ± 2.7 25.1 ± 1.3 4n 3-CH 3 -Ph 4 77.4 ± 1.5 42.9 ± 3.2 78.4 ± 0.6 54.7 ± 2.1 28.5 ± 3.4 17.7 ± 1.6 4o 4-CH 3 -Ph 4 83.3 ± 0.8 50.5 ± 2.3 74.9 ± 0.3 49.6 ± 2.1 90.4 ± 0.4 72.0 ± 0.9 4p 4-OCH 3 -Ph 4 27.1 ± 1.9 20.3 ± 1.4 80.8 ± 1.7 56.1 ± 2.2 25.9 ± 3.5 14.±5.8 4q 3-Cl-Ph 4 23.7 ± 2.8 19.9 ± 2.8 47.7 ± 1.3 34.4 ± 1.5 48.4 ± 1.2 35.4 ± 1.5 4r 4-Cl-Ph 4 24.5 ± 1.3 16.8 ± 1.5 26.7 ± 2.4 12.8 ± 1.9 62.6 ± 0.7 39.2 ± 2.9 4 s 3-Br-Ph 4 21.9 ± 1.5 14.7 ± 1.4 45.2 ± 1.5 21.1 ± 3.9 22.2 ± 2.5 12.5 ± 3.4 4t 4-Br-Ph 4 20.2 ± 2.5 17.7 ± 1.2 26.3 ± 4.5 21.6 ± 2.4 44.5 ± 3.8 33.0 ± 1.9 4u 3-F-Ph 4 45.5 ± 3.4 29.2 ± 6.3 23.8 ± 5.4 18.5 ± 1.0 53.4 ± 1.7 39.4 ± 2.2 4v 4-F-Ph 4 27.8 ± 1.5 19.7 ± 4.8 32.6 ± 1.9 27.9 ± 3.6 57.5 ± 1.3 37.5 ± 2.7 4w furan-2-yl 4 29.1 ± 0.8 20.7 ± 1.3 44.4 ± 0.7 28.8 ± 3.0 80.7 ± 1.8 59.1 ± 1.5 4x pyridin-4-yl 4 41.8 ± 3.7 26.2 ± 2.6 68.6 ± 3.5 45.6 ± 2.5 61.9 ± 1.2 33.2 ± 4.4 My b 44.9 ± 1.4 27.5 ± 3.01 44.0 ± 1.2 33.3 ± 0.9 50.7 ± 2.3 29.6 ± 1.1 TC c 55.0 ± 0.7 34.6 ± 0.9 49.5 ± 0.3 36.5 ± 1.0 60.1 ± 2.1 41.3 ± 2.5 BT c 64.6 ± 1.0 43.4 ± 1.4 63.9 ± 1.0 44.5 ± 0.7 71.7 ± 2.0 52.4 ± 1.8 a Average of three replicates. b The lead compound of myricetin. c The commercial bactericides bismerthiazol (BT) and thiediazole copper (TC). Based on the preliminary bioassays results in Table 2 , the EC 50 values of some target compounds against Xac , Xoo and Rs , were indicated in Table 3 , that compounds 4b , 4c , 4 h and 4o exhibited fine antibacterial activities against Xac , with EC 50 values of 30.8, 15.5, 28.2, and 29.2 µg/mL, respectively, which exceeded BT (51.7 µg/mL), and TC (77.9 µg/mL). 4c , 4d , 4 h , 4n and 4p demonstrated good inhibitory effects against Xoo with an EC 50 value of 14.9, 30.6, 23.7, 28.6 and 24.8 µg/mL, which were better than that of BT (70.1 µg/mL) and TC (95.8 µg/mL). Compounds 4c , 4d , 4 h , 4 k , 4 l and 4o have better antibacterial activity against Rs with the EC 50 values of 16.0, 23.1, 14.7, 17.5, 24.4, 16.0, and 29.4 µg/mL, respectively, which were superior to that of BT (52.8 µg/mL) and TC (72.1 µg/mL). Table 3 EC50 values of the title compounds against Xac, Xoo and Rs in vitroa Tested bacterial Compds. Toxic regression equation r 2 EC 50 /(µg/mL) Xac 4b y = 1.5705 x + 2.6602 0.9826 30.9 ± 2.0 4c y = 1.9107 x + 2.7256 0.9912 15.5 ± 1.7 4d y = 1.5736 x + 2.5280 0.9825 37.2 ± 2.1 4 h y = 1.7100 x + 2.5176 0.9809 28.3 ± 1.1 4j y = 1.4978 x + 2.6114 0.9873 39.3 ± 0.9 4n y = 1.6002 x + 2.5541 0.9947 33.7 ± 2.2 4o y = 1.7781 x + 2.3894 0.9811 29.4 ± 2.4 BT c y = 1.3743 x + 2.6450 0.9854 51.7 ± 2.0 TC c y = 1.3153 x + 2.5117 0.9822 77.9 ± 1.7 Xoo 4c y = 1.4639 x + 3.2826 0.9906 14.9 ± 0.9 4d y = 1.2237 x + 3.1804 0.9693 30.7 ± 1.6 4 h y = 1.4072 x + 3.0639 0.9961 23.8 ± 1.8 4 m y = 1.2358 x + 3.1996 0.9773 28.6 ± 2.6 4o y = 1.2425 x + 3.1428 0.9892 31.2 ± 0.9 4p y = 1.3657 x + 3.0943 0.9978 24.8 ± 1.1 BT c y = 1.3199 x + 2.5633 0.9848 70.1 ± 1.9 TC c y = 1.0632 x + 2.8928 0.9796 95.8 ± 2.7 RS 4c y = 1.6321 x + 3.0312 0.9929 16.1 ± 2.3 4d y = 1.4199 x + 3.0625 0.9780 23.1 ± 1.3 4 h y = 1.6908 x + 3.0236 0.9969 14.7 ± 1.2 4 k y = 1.4931 x + 3.1422 0.9857 17.5 ± 2.0 4 l y = 1.4276 x + 3.0175 0.9801 24.8 ± 1.0 4o y = 1.5422 x + 3.1423 0.9926 16.0 ± 1.3 4w y = 1.4597 x + 2.8546 0.9833 29.5 ± 2.5 BT c y = 1.4267 x + 2.5425 0.9543 52.8 ± 3.3 TC c y = 1.2906 x + 2.5962 0.9821 72.1 ± 2.1 a Average of three replicates. c The commercial agricultural antibacterial agents bismerthiazol (BT) and thiodiazole-copper (TC) were used as control agents. Structure–activity relationship analysis of the antibacterial activities. As indicated in Tables 2 , Table 3 , most of target compounds showed significant antibacterial activities against Xac , Xoo and Rs , the R groups had significant impact on the antibacterial activity, for example, 4c (n = 3, R = 4-CH 3 -Ph), 4 h (n = 3,R = 3-F-Ph), 4o (n = 4, R = 4-CH 3 -Ph) demonstrated a fine inhibitory effect against Xac with the EC 50 values of 15.5, 28.2 and 29.3 µg/mL, which were better than those of BT (51.7 µg/mL), andTC (77.9 µg /mL) and other substituents. Compounds 4c (n = 3, R = 4-CH 3 -Ph), 4d (n = 3, R = 4-OCH 3 -Ph) and 4p (n = 4, R = 4-OCH 3 -Ph) demonstrated good inhibitory effects against Xoo with an EC 50 value of 14.9, 23.7 and 24.8 µg/mL, which were better than that of BT (70.1 µg/mL) and TC (95.8 µg/mL). The presence of donor electron groups and heterocycles may effectively enhance the antibacterial activity against Rs , such as compounds 4c (n = 3, R = 4-CH 3 -Ph), 4d (n = 3 , R = 4-OCH 3 -Ph), 4 k (n = 3, R = furan), 4 l (n = 3, R = pyridyl) and 4o (n = 4, R = 4-CH 3 -Ph) have better antibacterial activity against Rs with the EC 50 values of 16.0, 23.1, 17.5, 24.4 and 16.0 µg/mL, respectively, which were superior to that of BT (52.8 µg/mL) and TC (72.1 µg/mL). From this analysis, when n = 3, R is 4-CH 3 -Ph, 4-CH 3 O-Ph, 3-F-Ph, the bioactivity of compounds are higher than that of n = 4, R is 4-CH 3 -Ph, 4-CH 3 O-Ph, 3-F-Ph, the activity of the para-substituted by -CH 3 , -OCH 3 and other group on the benzene is greater than the meta-substituted. Meanwhile, R was substituted with 3-F-Ph groups, the corresponding compound exhibit remarkable antibacterial activities against Xac , Xoo and Rs . In vivo bioactivity of 4c against rice bacterial leaf blight The experiments of 4c against rice bacterial leaf blight was determined using a leaf-cutting method. Shown in Table 4 and Fig. 4 , when the concentration of compound 4c was 200 µg.mL − 1 , the curative activity against bacterial blight of rice was 42.4%. This result was better than that of BT (35.2%) and TC (30.8%). Furthermore, compound 4c demonstrated excellent protection activity against bacterial blight of rice with the percentage inhibition of 49.2%, which was superior to BT (39.1%) and TC (27.3%). These results suggests that compound 4c effectively prevents the infection of Xanthomonas oryzae of rice. Scanning electron microscopy (SEM) studies The mechanism of compound against RS and Xoo were analyzed by SEM [ 39 , 40 ]. As shown in Fig. 5 , the surface morphology of Xoo were smooth and remains intact without compound to treatment, (Fig. 5 A). When the bacteria was treated with compound 4c at concentration of 50 ppm, bacteria cell membrane began to appear different degrees wrinkled (Fig. 5 B). as the concentration of compound increased to 100 ppm, the bacterial cell membrane showed invagination and rupture(Fig. 5 C). Therefore, that compound 4c destroyed the cell membrane structure, to achieve the purpose of antibacterial. Methods And Materials Chemistry All solvents and reagents were purchased from Shanghai Titan Scientific Co., Ltd, and were analytical grade or chemically pure. The melting point of all compounds ( 4a-4x ) was determined by the X-4B melting point apparatus ((Beijing Tech Instrument Co, Beijing. China). 1 H NMR, 13 C NMR and 19 F NMR were obtained on Bruker Ascend-400 spectrometer (Bruker Optics, Germany) Tetramethylsilane (TMS) as internal standard and DMSO was used as solvent; Mass spectral studies were performed on a quadrupole electrostatic field orbitrap mass spectrograph (Thermo Scientific, USA). The synthetic route of pyrimidine-containing 4 H -Chromen-4-one derivatives was shown in Scheme 1 . Intermediates 1 were prepared according to the reported methods. [ 26 , 41 , 42 ] General synthesis procedure for intermediate 1. Based on the previous reported method [ 41 , 42 ], the ethyl cyanoacetate (5 mmol), substituted aromatic aldehyde (5 mmol), thiourea (5 mmol) and anhydrous K 2 CO 3 (7.5 mmol) were added in ethanol (50 mL) then refluxed for about 4 – 6 h, after the reaction was completed (monitoring the reaction by TLC), mixture was cooled to room temperature and diluted with ice water, a large amount of solids precipitated as the pH was adjusted with glacial acetic acid to weak acidity, solids were filtered and dried with suction, recrystallized with absolute ethanol to obtain Intermediate 1 General synthesis procedures for intermediate 2 Myricetin as raw material, iodomethane as the methylation reagent and anhydrous K 2 CO 3 , heated to reflux in DMF and then extracted with methylene chloride, deglycosylation with concentrated hydrochloric acid under reflux in ethanol to prepare 3-hydroxy-3',4',5',5,7- pentamethoxymyricetin (Intermediate 2 ). General synthesis procedures for intermediate 3 Intermediate 2 (2 mmol) and K 2 CO 3 (3 mmol) are dissolved in certain amount of N , N -dimethylformamide (DMF). After the solution had been stirred at room temperature for 0.5 – 1 h, the different dibromoalkane (2 mmol) was added and reaction system continued at room temperature for 10 h. Mixture was dispersed in 50 mL ice water when reaction was completed (reaction was monitored by TLC) so a white solid was precipitated, sample was passed through a suction filter to remove the liquid, solid was continuously stirred in a mixed solution of 30 mL petroleum ether and ethyl acetate for 3–4 hours, then filtered and dried under reduced pressure to obtain Intermediate 3 . General synthesis procedures for title compounds 4 A solution of intermediates 1 (3 mmol), intermediates 3 (3 mmol) and K 2 CO 3 (4.5 mmol) in DMF (40 mL) was stirred under reflux for 4–5 h, after reaction was completed (reaction was monitored by TLC), the mixture was cooled to room temperature then poured into 80 mL ice water and extracted with ethyl acetate (3 × 30 mL), organic layer was washed with 5% hydrochloric acid solution, saturated NaHCO 3 aqueous solution, saturated NaCl solution successively and dried with anhydrous Na 2 SO 4 , solvent was removed under vacuum and crude product was separated by column chromatography with petroleum ether/ethyl acetate ( V:V = 1:1) to obtain the title compound 4a . Based on the similar method, the title compounds 4b - 4x were prepared. 2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile (4a) : white solid, m.p. 144.3-145.8 °C; yield: 41.3%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.94 (d, J = 7.3 Hz, 2H, Ph-H), 7.56 (d, J = 7.0 Hz, 1H, Ph-H), 7.50 (t, J = 7.2 Hz, 2H, Ph-H), 7.34 (s, 2H, Ph-H), 6.84 (s, 1H, Ph-H), 6.50 (s, 1H, Ph-H), 4.03 (s, 2H, -O- CH 2 CH 2 CH 2 -), 3.90 (s, 3H, Ph-OCH 3 ), 3.85 (s, 3H, Ph-OCH 3 ), 3.81 (s, 6H, 2 × Ph-OCH 3 ), 3.72 (s, 3H, Ph-OCH 3 ), 3.39 (s, 2H, -CH 2 CH 2 CH 2 -S-), 2.12 (d, J = 5.7 Hz, 2H, -CH 2 CH 2 CH 2 -); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.57, 164.27, 160.77, 158.65, 153.17, 152.21, 140.16, 139.89, 132.18, 129.08, 128.99, 125.94, 116.45, 108.88, 106.12, 96.41, 93.60, 93.39, 70.50, 60.63, 56.57, 56.49, 30.06, 27.80; HRMS calcd for C 34 H 31 N 3 O 9 S [M + H] + : 658.1854, found 658.1851. 2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-4-(m-tolyl)-1,6-dihydropyrimidine-5-carbonitrile (4b) : white solid, m.p. 231.6-232.8 °C; yield: 67.2%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.71 (s, 2H, Ph-H), 7.37 (d, J = 6.9 Hz, 2H, Ph-H), 7.34 (s, 2H, Ph-H), 6.85 (d, J = 2.2 Hz, 1H, Ph-H), 6.50 (d, J = 2.2 Hz, 1H, Ph-H), 4.02 (t, J = 5.8 Hz, 2H, -O- CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.85 (s, 3H, Ph-OCH 3 ), 3.80 (s, 6H, 2 × Ph-OCH 3 ), 3.72 (s, 3H, Ph-OCH 3 ), 3.34 (s, 2H, O-CH 2 CH 2 CH 2 -S-), 2.31 (s, 3H, Ph-CH 3 ), 2.15–2.04 (m, 2H, -CH 2 CH 2 CH 2 -); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.56, 167.64, 164.26, 160.75, 158.65, 153.16, 152.18, 140.20, 139.82, 138.29, 132.64, 129.49, 128.85, 126.31, 125.94, 108.85, 106.03, 96.41, 93.57, 70.55, 60.63, 56.53, 56.45, 30.17, 27.74, 21.32; HRMS calcd for C 35 H 33 N 3 O 9 S [M + H] + : 672.2010, found 672.1999. 2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-4-(p-tolyl)-1,6-dihydropyrimidine-5-carbonitrile ( 4c ) : White solid, m.p. 201.8-203.6 °C; yield: 30.3%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.85 (d, J = 8.1 Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 7.27 (d, J = 8.1 Hz, 2H, Ph-H), 6.85 (d, J = 2.1 Hz, 1H, Ph-H), 6.51 (d, J = 2.1 Hz, 1H, Ph-H), 4.03 (t, J = 5.9 Hz, 2H, -O- CH 2 CH 2 CH 2 -S-), 3.91 (s, 3H, Ph-OCH 3 ), 3.86 (s, 3H, Ph-OCH 3 ), 3.82 (s, 6H, 2 × Ph-OCH 3 ), 3.72 (s, 3H, Ph-OCH 3 ), 3.36 (d, J = 6.5 Hz, 2H, -O-CH 2 CH 2 CH 2 -S-), 2.34 (s, 3H, Ph-CH 3 ), 2.12 (dd, J = 12.8, 6.3 Hz, 2H, -O-CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.57, 166.16, 164.28, 160.78, 158.66, 153.18, 152.18, 142.51, 140.17, 139.90, 132.85, 129.56, 129.18, 125.94, 116.59, 108.90, 106.11, 96.42, 93.61, 92.75, 70.53, 60.61, 56.77, 56.39, 55.39, 30.13, 27.78, 21.51; HRMS calcd for C 35 H 33 N 3 O 9 S [M + H] + : 671.1932, found 671.1905. 2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile ( 4d ) : white solid, m.p. 179.2-181.1 °C; yield: 32.5%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.01 (d, J = 8.8 Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 7.02 (d, J = 8.9 Hz, 2H, Ph-H), 6.84 (d, J = 2.2 Hz, 1H, Ph-H), 6.50 (d, J = 2.2 Hz, 1H, Ph-H), 4.04 (t, J = 5.9 Hz, 2H, -O- CH 2 CH 2 CH 2 -S-), 3.91 (s, 3H, Ph-OCH 3 ), 3.86 (s, 3H, Ph-OCH 3 ), 3.81 (s, 6H, 2 × Ph-OCH 3 ), 3.80 (s, 3H, Ph-OCH 3 ), 3.72 (s, 3H, Ph-OCH 3 ), 3.39 (d, J = 6.9 Hz, 2H, -O-CH 2 CH 2 CH 2 -S-), 2.17–2.07 (m, 2H, -O-CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.57, 164.27, 162.66, 160.77, 158.65, 153.17, 152.14, 140.19, 139.90, 131.27, 125.93, 116.88, 114.42, 108.88, 106.09, 96.42, 93.60, 70.51, 60.62, 56.57, 56.52, 56.48, 55.88, 55.39, 30.16, 27.76; HRMS calcd for C 35 H 33 N 3 O 10 S [M + H] + : 688.1959, found 688.1952. 4-(3-chlorophenyl)-2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile ( 4e ) : Brown solid, m.p. 119.6-121.9 °C; yield: 23.9%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.94–7.84 (m, 2H, Ph-H), 7.62 (d, J = 8.0 Hz, 1H, Ph-H), 7.53 (t, J = 7.9 Hz, 1H, Ph-H), 7.33 (s, 2H, Ph-H), 6.83 (d, J = 1.6 Hz, 1H, Ph-H), 6.50 (s, 1H, Ph-H), 4.02 (t, J = 5.5 Hz, 2H, -O- CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.85 (s, 3H, Ph-OCH 3 ), 3.81 (s, 6H, 2 × Ph-OCH 3 ), 3.72 (s, 3H, Ph-OCH 3 ), 3.35 (d, J = 6.3 Hz, 2H, -O-CH 2 CH 2 CH 2 -S-), 2.13–2.02 (m, 2H, -O-CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.58, 165.98, 164.24, 160.75, 158.64, 153.14, 152.19, 140.21, 139.85, 137.87, 133.66, 131.70, 130.91, 128.69, 127.77, 125.96, 108.87, 106.08, 96.39, 93.57, 70.49, 60.63, 56.56, 56.51, 56.47, 30.11, 27.76; HRMS calcd for C 34 H 30 ClN 3 O 9 S [M + H] + : 692.1464, found 692.1455. 4-(4-chlorophenyl)-2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile ( 4f ) : White solid, m.p. 182.4-183.8 °C; yield: 41.7%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.93 (d, J = 8.5 Hz, 2H, Ph-H), 7.55 (d, J = 8.5 Hz, 2H, Ph-H), 7.36 (s, 2H, Ph-H), 6.84 (d, J = 2.0 Hz, 1H, Ph-H), 6.50 (d, J = 2.0 Hz, 1H, Ph-H), 4.03 (t, J = 6.0 Hz, 2H, -O- CH 2 CH 2 CH 2 -S-), 3.91 (s, 3H, Ph-OCH 3 ), 3.87 (s, 3H, Ph-OCH 3 ), 3.83 (s, 6H, 2 × Ph-OCH 3 ), 3.73 (s, 3H, Ph-OCH 3 ), 3.28 (d, J = 6.9 Hz, 2H, -O-CH 2 CH 2 CH 2 -S-), 2.14–2.06 (m, 2H, -O-CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.59, 166.22, 164.26, 160.76, 158.65, 153.18, 152.15, 140.18, 139.89, 136.55, 135.01, 130.89, 129.03, 125.95, 108.89, 106.09, 96.42, 93.61, 70.60, 60.62, 56.59, 56.50, 30.29, 27.55; HRMS calcd for C 34 H 30 ClN 3 O 9 S [M + H] + : 692.1640, found 692.1450. 4-(4-bromophenyl)-2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile ( 4 g ): White solid, m.p. 183.2-185.1 °C; yield: 25.7%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.88 (d, J = 8.5 Hz, 2H, Ph-H), 7.70 (d, J = 8.5 Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 6.85 (d, J = 1.8 Hz, 1H, Ph-H), 6.51 (d, J = 1.7 Hz, 1H, Ph-H), 4.03 (s, 2H, -O- CH 2 CH 2 CH 2 -S-), 3.91 (s, 3H, Ph-OCH 3 ), 3.87 (s, 3H, Ph-OCH 3 ), 3.83 (s, 6H, 2 × Ph-OCH 3 ), 3.73 (s, 3H, Ph-OCH 3 ), 3.37 (s, 2H, -O-CH 2 CH 2 CH 2 -S-), 2.16–2.06 (m, 2H, -O-CH 2 CH 2 CH 2 -S-). 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.59, 166.41, 164.28, 160.76, 158.65, 153.18, 152.17, 140.14, 139.89, 134.84, 132.08, 131.16, 125.96, 116.36, 108.88, 106.07, 96.43, 93.52, 70.48, 60.63, 56.63, 56.50, 30.16, 27.74; HRMS calcd for C 34 H 30 BrN 3 O 9 S [M + H] + : 736.0959, found 736.0927. 2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-4-(3-fluorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile ( 4 h ): Brown solid, m.p. 204.6-206.4 °C; yield: 57.0%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.78 (d, J = 7.8 Hz, 1H, Ph-H), 7.70 (d, J = 9.8 Hz, 1H, Ph-H), 7.55 (dd, J = 14.0, 8.0 Hz, 1H, Ph-H), 7.40 (td, J = 8.5, 2.3 Hz, 1H, Ph-H), 7.34 (s, 2H, Ph-H), 6.83 (d, J = 2.1 Hz, 1H, Ph-H), 6.49 (d, J = 2.1 Hz, 1H, Ph-H), 4.02 (t, J = 5.8 Hz, 2H, -O- CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.85 (s, 3H, Ph-OCH 3 ), 3.81 (s, 6H, 2 × Ph-OCH 3 ), 3.72 (s, 3H, Ph-OCH 3 ), 3.34 (d, J = 6.8 Hz, 2H, -O-CH 2 CH 2 CH 2 -S-), 2.16–2.03 (m, 2H, -O-CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.59, 166.00, 164.24, 163.41, 160.98, 160.75, 158.64, 153.15, 152.19, 140.18, 139.85, 131.15, 131.07, 125.95, 125.28, 118.86, 118.66, 116.75, 115.94, 115.71, 108.87, 106.07, 96.39, 93.57, 70.52, 60.62, 56.55, 56.51, 56.46, 30.13, 27.72; 19 F NMR (376 MHz, DMSO -d 6 ) δ -112.23 (d, J = 6.1 Hz); HRMS calcd for C 34 H 30 FN 3 O 9 S [M + H] + : 676.1760, found 676.1755. 2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-4-(4-fluorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile ( 4i ): White solid, m.p. 197.5-199.4 °C; yield: 31.7%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.05 (dd, J = 8.1, 5.6 Hz, 2H, Ph-H), 7.39–7.30 (m, 4H, Ph-H), 6.84 (d, J = 1.3 Hz, 1H, Ph-H), 6.50 (s, 1H, Ph-H), 4.02 (t, J = 5.9 Hz, 2H, -O- CH 2 CH 2 CH 2 -S-), 3.91 (s, 3H, Ph-OCH 3 ), 3.86 (s, 3H, Ph-OCH 3 ), 3.82 (s, 6H, 2 × Ph-OCH 3 ), 3.73 (s, 3H, Ph-OCH 3 ), 3.37 (d, J = 6.5 Hz, 2H, -O-CH 2 CH 2 CH 2 -S-), 2.18–2.06 (m, 2H, -O-CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.57, 166.40, 165.71, 164.25, 163.22, 160.72, 158.64, 153.16, 152.16, 140.13, 139.83, 131.99, 131.89, 125.92, 116.46, 116.25, 116.03, 108.85, 106.01, 96.40, 93.58, 93.21, 70.42, 60.61, 56.51, 56.46, 30.10, 27.72; 19 F NMR (376 MHz, DMSO- d 6 ) δ -107.84; HRMS calcd for C 34 H 30 FN 3 O 9 S [M + H] + : 676.1760, found 676.1755. 2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-4-(thiophen-2-yl)-1,6-dihydropyrimidine-5-carbonitrile (4j) : Gray solid, m.p. 145.4-147.8 °C; yield: 50.6%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.22 (d, J = 3.8 Hz, 1H, thienyl-H), 7.94 (d, J = 5.0 Hz, 1H, thienyl-H), 7.36 (s, 2H, Ph-H), 7.31–7.27 (m, 1H, thienyl -H), 6.82 (d, J = 2.1 Hz, 1H, Ph-H), 6.49 (d, J = 2.1 Hz, 1H, Ph-H), 4.07 (t, J = 6.0 Hz, 2H, -O- CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.85 (s, 3H, Ph-OCH 3 ), 3.84 (s, 6H, 2 × Ph-OCH 3 ), 3.73 (s, 3H, Ph-OCH 3 ), 3.30 (d, J = 7.0 Hz, 2H -O-CH 2 CH 2 CH 2 -S-), 2.17–2.09 (m, 2H -O-CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.60, 164.24, 160.75, 158.95, 158.64, 153.16, 152.23, 140.33, 140.17, 139.87, 134.86, 131.58, 129.84, 125.97, 117.16, 108.88, 106.16, 96.40, 93.57, 88.04, 70.60, 60.64, 56.57, 56.51, 30.09, 27.86; HRMS calcd for C 33 H 28 N 4 O 3 [M + H] + : 664.1418, found 664.1411. 2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-4-(furan-2-yl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (4 k) : Gray solid, m.p. 229.4-231.3 °C; yield: 60.3%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.09 (d, J = 0.8 Hz, 1H, furyl-H), 7.47 (d, J = 3.5 Hz, 1H, furyl-H), 7.36 (s, 2H, Ph-H), 6.83 (d, J = 2.2 Hz, 1H, furyl-H), 6.70 (dd, J = 3.5, 1.7 Hz, 1H, Ph-H), 6.49 (d, J = 2.2 Hz, 1H, Ph-H), 4.06 (t, J = 6.0 Hz, 2H, -O- CH 2 CH 2 CH 2 -S-), 3.91 (s, 3H, Ph-OCH 3 ), 3.86 (s, 3H, Ph-OCH 3 ), 3.84 (s, 6H, 2 × Ph-OCH 3 ), 3.73 (s, 3H, Ph-OCH 3 ), 3.35 (s, 2H, -O-CH 2 CH 2 CH 2 -S-), 2.15–2.06 (m, 2H, -O-CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.59, 164.25, 160.77, 158.64, 154.94, 153.17, 152.21, 149.92, 148.42, 140.17, 139.91, 125.94, 118.62, 115.85, 113.63, 108.90, 106.14, 96.41, 93.58, 88.01, 70.64, 60.63, 56.57, 56.51, 55.39, 30.06, 27.81; HRMS calcd for C 32 H 29 N 3 O 10 S [M + H] + : 648.1646, found 648.1638. 2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-4-(pyridin-4-yl)-1,6-dihydropyrimidine-5-carbonitrile (4 l) : Brown solid, m.p. 147.8-149.8 °C; yield: 50.2%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.75 (d, J = 5.8 Hz, 2H, Piperidinyl-H), 7.85 (dd, J = 4.5, 1.5 Hz, 2H, Piperidinyl-H), 7.34 (s, 2H, Ph-H), 6.84 (d, J = 2.1 Hz, 1H, Ph-H), 6.50 (d, J = 2.1 Hz, 1H, Ph-H), 4.03 (t, J = 6.0 Hz, 2H, -O- CH 2 CH 2 CH 2 -S-), 3.91 (s, 3H, Ph-OCH 3 ), 3.86 (s, 3H, Ph-OCH 3 ), 3.82 (s, 6H, 2 × Ph-OCH 3 ), 3.73 (s, 3H, Ph-OCH 3 ), 3.36 (t, J = 7.0 Hz, 2H, -O-CH 2 CH 2 CH 2 -S-), 2.15–2.07 (m, 2H, -O-CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.58, 167.58, 165.46, 164.28, 160.77, 158.65, 153.18, 152.20, 150.65, 142.98, 140.14, 139.92, 125.93, 122.83, 115.85, 108.89, 106.13, 96.42, 94.67, 93.62, 70.46, 60.65, 56.58, 56.52, 30.01, 27.84; HRMS calcd for C 33 H 30 N 4 O 9 S [M + H] + : 659.1806, found 659.1811. 2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile (4 m) : Yellow solidd, m.p. 227.0-228.5 °C; yield: 42.9%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.93–7.87 (m, 2H, Ph-H), 7.56–7.46 (m, 3H Ph-H), 7.33 (m, 2H, Ph-H), 6.83 (d, J = 2.1 Hz, 1H, Ph-H), 6.49 (d, J = 2.0 Hz, 1H, Ph-H), 3.95 (t, J = 5.8 Hz, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.84 (s, 3H, Ph-OCH 3 ), 3.83 (d, J = 5.0 Hz, 6H, 2 × Ph-OCH 3 ), 3.74 (s, 3H, Ph-OCH 3 ), 3.27 (t, J = 6.7 Hz, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 1.81 (dd, J = 14.0, 6.5 Hz, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.63, 166.53, 164.23, 160.74, 158.62, 153.13, 152.05, 140.27, 139.86, 132.10, 129.03, 128.95, 125.99, 116.44, 108.90, 106.13, 96.38, 93.56, 71.38, 60.65 1, 56.56, 56.51, 30.44, 29.00, 26.05; HRMS calcd for C 35 H 33 N 3 O 9 S [M + H] + : 672.2010, found 672.2007. 2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-4-(m-tolyl)-1,6-dihydropyrimidine-5-carbonitrile (4n) : Yellow solidd, m.p. 207.6-209.5 °C; yield: 45.8%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.69 (d, J = 8.8 Hz, 2H, Ph-H), 7.41–7.35 (m, 2H, Ph-H), 7.34 (s, 2H, Ph-H), 6.82 (d, J = 2.2 Hz, 1H, Ph-H), 6.49 (d, J = 2.3 Hz, 1H, Ph-H), 3.96 (t, J = 5.7 Hz, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.84 (s, 3H, Ph-OCH 3 ), 3.83 (s, 6H, 2 × Ph-OCH 3 ), 3.26 (t, J = 6.8 Hz, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 2.32 (s, 3H, Ph-OCH 3 ), 1.88–1.72 (m, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.60, 164.22, 160.74, 158.61, 153.12, 152.03, 140.26, 139.87, 138.30, 132.71, 129.47, 128.84, 126.26, 125.98, 116.41, 108.90, 106.14, 96.36, 93.55, 71.36, 60.64, 56.50, 30.42, 29.01, 26.14, 21.33; HRMS calcd for C 36 H 35 N 3 O 9 S [M + H] + : 686.2167, found 686.2161. 2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-4-(p-tolyl)-1,6-dihydropyrimidine-5-carbonitrile (4o) : White solid, m.p. 229.8-231.2 °C; yield: 59.1%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.82 (d, J = 8.2 Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 7.27 (d, J = 8.1 Hz, 2H, Ph-H), 6.83 (d, J = 2.2 Hz, 1H, Ph-H), 6.49 (d, J = 2.2 Hz, 1H, Ph-H), 3.97 (t, J = 5.8 Hz, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.84 (s, 9H,3 × Ph-OCH 3 ), 3.27 (t, J = 6.7 Hz, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 2.32 (s, 3H, Ph-OCH 3 ), 1.81 (dd, J = 11.6, 6.6 Hz, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.62, 167.36, 166.21, 164.23, 160.75, 158.6, 153.12, 151.97, 142.47, 140.26, 139.87, 132.85, 129.51, 129.10, 125.98, 116.57, 108.89, 106.11, 96.37, 93.56, 92.76, 71.33, 60.64, 56.54, 56.51, 30.38, 28.96, 26.12, 21.45; HRMS calcd for C 36 H 35 N 3 O 9 S [M + H] + : 686.2167, found 686.2191. 2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (4p) : Yellow solidd, m.p. 236.4-237.8 °C; yield: 51.9%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.97 (d, J = 8.9 Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 7.04 (d, J = 9.0 Hz, 2H, Ph-H), 6.82 (d, J = 2.2 Hz, 1H, Ph-H), 6.48 (d, J = 2.2 Hz, 1H, Ph-H), 3.97 (t, J = 5.6 Hz, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.84 (s, 9H, 3 × Ph-OCH 3 ), 3.80 (s, 3H, Ph-OCH 3 ), 3.74 (s, 3H, Ph-OCH 3 ), 3.28 (t, J = 6.6 Hz, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 1.88–1.76 (m, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.64, 164.2, 162.63, 160.74, 158.59, 153.12, 151.95, 140.28, 139.88, 131.16, 125.98, 116.90, 114.39, 108.87, 106.11, 96.36, 93.55, 71.35, 60.64, 56.51, 55.87, 30.38, 28.99, 26.12; HRMS calcd for C 36 H 35 N 3 O 10 S [M] + : 701.2038, found 701.2026. 4-(3-chlorophenyl)-2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (4q) : Yellow solidd, m.p. 137.2-139.2 °C; yield: 41.8%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.81 (dd, J = 7.2, 1.3 Hz, 2H Ph-H), 7.59–7.48 (m, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 6.82 (d, J = 2.2 Hz, 1H, Ph-H), 6.49 (d, J = 2.2 Hz, 1H, Ph-H), 3.95 (s, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.84 (s, 9H, 3 × Ph-OCH 3 ), 3.74 (s, 3H, Ph-OCH 3 ), 3.16 (s, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 1.79 (s, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.63, 165.88, 164.21, 160.75, 158.61, 153.12, 152.03, 140.30, 139.86, 133.53, 131.09, 130.76, 128.51, 127.53, 126.01, 108.91, 106.14, 96.36, 93.55, 71.47, 60.64, 56.52, 56.50, 30.24, 29.10, 26.25; HRMS calcd for C 35 H 32 ClN 3 O 9 S [M + H] + : 706.1621, found706.1605. 4-(4-chlorophenyl)-2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (4r) : Yellow solidd, m.p. 129.5-131.8 °C; yield: 61.5%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.84 (d, J = 8.6 Hz, 2H, Ph-H), 7.70 (d, J = 8.6 Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 6.83 (d, J = 2.2 Hz, 1H, Ph-H), 6.49 (d, J = 2.2 Hz, 1H, Ph-H), 3.96 (t, J = 5.8 Hz, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.91 (s, 3H, Ph-OCH 3 ), 3.85 (s, 3H, Ph-OCH 3 ), 3.84 (s, 6H, 2 × Ph-OCH 3 ), 3.74 (s, 3H, Ph-OCH 3 ), 3.27 (t, J = 6.8 Hz, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 1.81 (dd, J = 14.8, 6.6 Hz, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.65, 166.79, 166.44, 164.24, 160.75, 158.60, 153.13, 151.96, 140.28, 139.90, 134.84, 132.05, 131.06, 125.97, 116.27, 108.88, 106.13, 96.41, 93.59, 71.36, 60.65, 56.57, 56.53, 30.42, 28.93, 26.08; HRMS calcd for C 35 H 32 ClN 3 O 9 S [M + H] + : 706.1621, found 706.1592. 4-(3-bromophenyl)-2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (4 s) : Yellow solidd, m.p. 119.5-121.4 °C; yield: 30.5%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.99 (d, J = 1.7 Hz, 1H, Ph-H), 7.90 (d, J = 7.8 Hz, 1H, Ph-H), 7.73 (d, J = 7.9 Hz, 1H, Ph-H), 7.46 (t, J = 7.9 Hz, 1H, Ph-H), 7.35 (d, J = 9.9 Hz, 2H, Ph-H), 6.82 (d, J = 2.1 Hz, 1H, Ph-H, Ph-H), 6.49 (d, J = 1.9 Hz, 1H, Ph-H), 3.96 (s, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.84 (d, J = 3.1 Hz, 12H, 4 × Ph-OCH 3 ), 3.73 (d, J = 1.8 Hz, 3H, Ph-OCH 3 ), 3.26 (t, J = 6.5 Hz, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 1.80 (s, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.62, 165.89, 164.21, 160.73, 158.60, 153.11, 152.03, 140.26, 139.83, 137.89, 134.64, 131.56, 131.12, 128.06, 125.98, 122.05, 116.14, 108.89, 106.11, 96.36, 93.54, 71.37, 60.64, 56.50, 30.44, 28.97, 26.10; HRMS calcd for C 35 H 32 BrN 3 O 9 S [M + H] + : 750.1115, found 750.1126. 4-(4-bromophenyl)-2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (4t) : White solid, m.p. 153.6-155.4 °C; yield: 46.1%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.86–7.81 (m, 2H, Ph-H), 7.73–7.66 (m, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 6.83 (d, J = 2.2 Hz, 1H, Ph-H), 6.49 (d, J = 2.2 Hz, 1H, Ph-H), 3.96 (t, J = 5.8 Hz, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.91 (s, 3H, Ph-OCH 3 ), 3.85 (s, 3H, Ph-OCH 3 ), 3.84 (s, 6H, 2 × Ph-OCH 3 ), 3.74 (s, 3H, Ph-OCH 3 ), 3.27 (t, J = 6.8 Hz, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 1.81 (dd, J = 14.8, 6.6 Hz, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.65, 166.79, 166.44, 164.24, 160.75, 158.60, 153.13, 151.96, 140.28, 139.90, 134.84, 132.05, 131.06, 125.97, 116.27, 108.88, 106.13, 96.41, 93.59, 71.36, 60.65, 56.57, 56.53, 30.42, 28.93, 26.08; HRMS calcd for C 35 H 32 BrN 3 O 9 S [M + H] + : 750.1115, found 750.1108. 2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-4-(3-fluorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (4u) : White solid, m.p. 119.8-121.64 °C; yield: 70.8%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.73 (d, J = 7.9 Hz, 1H, Ph-H), 7.65 (dd, J = 9.8, 2.0 Hz, 1H, Ph-H), 7.55 (td, J = 8.0, 6.1 Hz, 1H, Ph-H), 7.41–7.36 (m, 1H, Ph-H), 7.35 (d, J = 3.9 Hz, 2H, Ph-H), 6.83 (d, J = 2.2 Hz, 1H, Ph-H), 6.48 (d, J = 2.2 Hz, 1H, Ph-H), 3.95 (t, J = 5.5 Hz, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.84 (s, 9H, 3 × Ph-OCH 3 ), 3.73 (s, 3H, Ph-OCH 3 ), 3.24 (t, J = 6.4 Hz, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 1.80 (d, J = 3.2 Hz, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.63, 164.21, 160.94, 160.73, 158.60, 153.12, 152.02, 140.27, 139.84, 131.09, 125.99, 125.22, 115.87, 115.64, 108.88, 106.10, 96.35, 93.53, 71.38, 60.64, 56.51, 30.41, 28.98, 26.04; 19 F NMR (376 MHz, DMSO- d 6 ) δ -112.28; HRMS calcd for C 35 H 32 FN 3 O 9 S [M + H] + : 690.1916, found 690.1915. 2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-4-(4-fluorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (4v) : White solid, m.p. 223.0-224.8 °C; yield: 25.3%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.99 (dd, J = 8.9, 5.5 Hz, 2H, Ph-H), 7.38–7.32 (m, 4H, Ph-H), 6.84 (d, J = 2.2 Hz, 1H, Ph-H), 6.50 (d, J = 2.2 Hz, 1H, Ph-H), 3.96 (t, J = 5.8 Hz, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.84 (d, J = 2.0 Hz, 9H, 3 × Ph-OCH 3 ), 3.74 (s, 3H, Ph-OCH 3 ), 3.27 (t, J = 6.7 Hz, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 1.81 (dd, J = 9.6, 4.5 Hz, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.67, 164.24, 160.72, 158.61, 153.12, 152.00, 140.27, 139.82, 131.81, 125.98, 116.54, 116.21, 115.99, 108.86, 106.07, 96.40, 93.56, 71.39, 60.64, 56.51, 30.39, 28.97, 26.07; 19 F NMR (376 MHz, DMSO) δ -105.82; HRMS calcd for C 35 H 32 FN 3 O 9 S [M + H] + : 690.1916, found 690.1894 . 2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-4-(furan-2-yl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (4w) : Black solid, m.p. 236.8-238.7 °C; yield: 73.2%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.10 (s, 1H, Ph-H), 7.45 (d, J = 3.4 Hz, 1H, Ph-H), 7.36 (d, J = 4.2 Hz, 2H, Ph-H), 6.82 (d, J = 2.2 Hz, 1H, Ph-H), 6.71 (dd, J = 3.5, 1.7 Hz, 1H, Ph-H), 6.49 (d, J = 2.1 Hz, 1H, Ph-H), 4.00 (d, J = 5.2 Hz, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.85 (s, 6H, 2 × Ph-OCH 3 ), 3.84 (s, 3H, Ph-OCH 3 ), 3.76–3.72 (m, 3H, Ph-OCH 3 ), 3.29 (s, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 1.81 (d, J = 2.9 Hz, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.67, 164.22, 160.71, 158.59, 154.86, 153.11, 151.97, 149.77, 148.57, 140.29, 139.80, 125.99, 118.73, 115.71, 113.67, 108.85, 106.03, 96.38, 93.53, 71.34, 60.65, 56.50, 30.29, 28.91, 26.04; HRMS calcd for C 33 H 31 N 3 O 10 S [M + H] + : 662.1803, found 662.1790. 2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-4-(pyridin-4-yl)-1,6-dihydropyrimidine-5-carbonitrile (4x) : Yellow solidd, m.p. 213.8-215.8 °C; yield:56.6%; 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.75 (d, J = 5.8 Hz, 2H, Ph-H), 7.81 (dd, J = 4.5, 1.6 Hz, 2H, Ph-H), 7.34 (s, 2H, Ph-H), 6.83 (d, J = 2.2 Hz, 1H, Ph-H), 6.49 (d, J = 2.2 Hz, 1H, Ph-H), 3.95 (t, J = 5.8 Hz, 2H, -O- CH 2 CH 2 CH 2 CH 2 -S-), 3.90 (s, 3H, Ph-OCH 3 ), 3.84 (s, 3H, Ph-OCH 3 ), 3.83 (s, 6H, 2 × Ph-OCH 3 ), 3.73 (s, 3H, Ph-OCH 3 ), 3.28 (t, J = 6.7 Hz, 2H, -O-CH 2 CH 2 CH 2 CH 2 -S-), 1.85–1.75 (m, 4H, -O-CH 2 CH 2 CH 2 CH 2 -S-); 13 C NMR (101 MHz, DMSO- d 6 ) δ 172.64, 167.52, 165.49, 164.23, 161.16, 160.72, 158.60, 153.12, 152.01, 150.62, 142.98, 140.27, 139.82, 125.97, 122.79, 115.76, 108.86, 106.07, 96.38, 94.82, 93.56, 71.35, 60.65, 56.55, 56.50, 30.52, 28.97, 25.97, 21.24; HRMS calcd for C 34 H 32 N 4 O 9 S [M + H] + : 673.1963, found 673.1943. Conclusions In summary, aiming to develop novel and high-efficient agents with better biological activities, a series of pyrimidine-containing 4 H -chromen-4-one derivatives were designed and synthesized. Antibacterial bioassys showed that most of compounds exhibited significant antibacterial activity against Xac , Xoo and Rs . Among them, the EC 50 values of compound 4c agains Xac and Xoo were 15.5 and 14.9 µg/mL respectively, which were better than BT (51.7, 70.1%, respectively) and TC (77.9, 95.8%, respectively), compounds 4 h displayed appreciable activity against Rs , with the EC 50 values of 14.7 µg/mL, the result superior to BT (and 52. 8 µg/mL) and TC (72.1 µg/mL). Compound 4c demonstrated excellent curative activity and protection activity against bacterial blight of rice with the percentage inhibition of 42.4 and 49.2%, respectively, which were better than BT (35.2, 39.1%, respectively) and TC (30.8, 27.3%, respectively). Furthermore, the mechanism of compound 4c against Xoo was confirmed by scanning electron microscope, the results showed that the compound destroyed the cell membrane structure of the bacteria, and the damage of the cell membrane was more serious as the concentration increased. These results indicated that the pyrimidine-containing 4 H -chromen-4-one derivatives possess better antibacterial activities and could be further studied as potential replacement templates in the search for novel antibacterial agents. Declarations Ethics approval and consent to participate This section are not applicable for this manuscript. Consent for publication This section are not applicable for this manuscript. Availability of data and material We have presented all our main data in the form of tables and figures. Meanwhile, all the copies of 1 H NMR, 13 C NMR, 19 F NMR and HRMS for the title compounds were presented in the Support Information. The datasets supporting the conclusions of the article are included within the article and the Support Information. Competing interests The authors declare that they have no competing interests. Funding We gratefully acknowledge the National Key Research and Development Program of China (No.2018YFD02011026), the National Nature Science Foundation of China (No. 21867003), the Science Fund of Guizhou Province (Nos. 20191105, 20192452, 20162533). Authors’ contributions This study is an outcome of constructive discussion with W Xue. SJ Su, M Chen carry out their synthesis and characterization experiments and carried out the 1 H NMR, 13 C NMR, 19 F NMR and HRMS spectral analyses, XM Tang and F Peng performed the antibacterial activity; TT Liu, Q Zhou, H Luo and M He assists in scanning electron microscope; SJ Su, M Chen were involved in the drafting of the manuscript and revising the manuscript. All authors read and approved the final manuscript. 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Pharmacol Res 122: 66–77 Gouhar RS, Kamel MM, Soliman AAF (2019) Synthesis and anticancer evaluation of some novel N,O,S heterocyclic compounds pendant to 3-methyl-5-cyano-6-(3,4-dimethoxyphenyl) pyrimidine and other related fused pyrimidines. J Heterocyclic Chem 21:1–12 Akranth M, Mymoona A, Mohammad S, Omprakash T, Mohammad MA (2014) Synthesis, 3D-QSAR and docking studies of pyrimidine nitrile-pyrazoline: a novel class of hybrid antimalarial agents. Med Chem Res 24: 1018–1037 Zhang Y, Wang BL, Zhan Y Z, Zhang LY, Li YH, Li ZM (2016) Synthesis and Biological Activities of Novel 5-(Pyridine-3-yl)-1,2,4-Triazole Mannich Bases and Bis-Mannich Bases Containing Piperazine Moiety. Chem J Chin U 37:1100–1107. Jin R, Liu J, Zhang G, Li J, Zhang S, Guo H (2018) Design, Synthesis, and Antifungal Activities of Novel 1,2,4-Triazole Schiff Base Derivatives. Chem. Biodivers 5: e1800263 Zhang PF, Guan AY, Xia XL, Sun XF, Liu CL (2019) Design, synthesis, and structure activity relationship of new arylpyrazole pyrimidine ether derivatives as fungicides. J Agric Food Chem 67：11893−11900 Bai XQ, Li CS, Cui MY, Song ZW, Zhou XY, Zhang C, Zhao Y, Zhang TY, Jiang TY (2019) Synthesis and molecular docking studies of novel pyrimidine derivatives as potential antibacterial agents.Mol Divers 24: 1-12 Jiang SC, Tang X, Chen M, He J, Su SJ, Liu LW, He M, Xue W (2020) Design, synthesis and antibacterial activities against Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. citri and Ralstonia solanacearum of novel myricetin derivatives containing sulfonamide moiety. Pest Manag Sci 76:853–860 Chen L, Wang PY, Li Z X, Zhou L, Wu ZB, Song BA, Yang S (2016) Antiviral and Antibacterial Activities of N -(4-Substituted phenyl) Acetamide Derivatives Bearing 1,3,4-Oxadiazole Moiety. Chin J Chem 34:1236−1244 Wang PY, Wang MW, Zeng D, Xiang M, Rao JR, Liu QQ, Liu LW, Wu Z.B, Li Z, Song BA, Yang S (2019) Rational Optimization and Action Mechanism of Novel Imidazole (or Imidazolium)-Labeled 1,3,4-Oxadiazole Thioethers as Promising Antibacterial Agents against Plant Bacterial Diseases. J Agric Food Chem 67: 3535–3545 Guo T, Xia RJ, Liu TT, Peng F, Tang XM, Zhou Q, Luo H, Xue W (2020) Synthesis, Biological Activity and Action Mechanism Study of Novel Chalcone Derivatives Containing Malonate. Chem Biodivers 17: e2000025 Gouhar RS, Kamel MM, Soliman AAF (2020) Synthesis and anticancer evaluation of some novel N,O,S heterocyclic compounds pendant to 3-methyl-5-cyano-6-(3,4-dimethoxyphenyl) pyrimidine and other related fused pyrimidines. J Heterocycl Chem 57: 69-80 Wang B, Zhao B, Pang LP, Zhao YD, Guo Q, Wang JW, Zheng YC, Zhang XH, Liu Y, Liu GY, Guo WG, Wang C, Li ZH, Mao XJ, Yu B, Ma LY (2017) LPE-1, an orally active pyrimidine derivative, inhibits growth and mobility of human esophageal cancers by targeting LSD1. Pharmacol Res 122 : 66 –77 Supplementary Files SupportingInformation.doc checkcif.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-92183","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":3536278,"identity":"76c052a5-c5ed-4f79-a730-296fba0ea53c","order_by":0,"name":"Shijun Su","email":"","orcid":"","institution":"Guizhou university","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shijun","middleName":"","lastName":"Su","suffix":""},{"id":3536279,"identity":"70c9be77-499c-451c-b6df-a01976dd9618","order_by":1,"name":"Mei Chen","email":"","orcid":"","institution":"Guizhou 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19:51:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-92183/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-92183/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":3060159,"identity":"aa3e38e9-6ba8-4a6b-aa5c-4f2b86a6847a","added_by":"auto","created_at":"2020-10-19 14:41:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":8256,"visible":true,"origin":"","legend":"Structure of myricetin ","description":"","filename":"1.PNG","url":"https://assets-eu.researchsquare.com/files/rs-92183/v1/ba04facabcee05321423abb8.PNG"},{"id":3060160,"identity":"3f8e01d8-d609-4bc5-b875-87fe09f6b1ac","added_by":"auto","created_at":"2020-10-19 14:41:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":285556,"visible":true,"origin":"","legend":"Design strategy for target molecules","description":"","filename":"2.PNG","url":"https://assets-eu.researchsquare.com/files/rs-92183/v1/51995142c71411feccd7436e.PNG"},{"id":3060161,"identity":"5478e10c-5abb-456a-bbec-d9e984793192","added_by":"auto","created_at":"2020-10-19 14:41:26","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":272679,"visible":true,"origin":"","legend":"Crystalline structure of compound 4g","description":"","filename":"3.PNG","url":"https://assets-eu.researchsquare.com/files/rs-92183/v1/04a3dc9d470fe96a013c08f5.PNG"},{"id":3060162,"identity":"6e3da557-d3a5-4564-9909-758fd06dc073","added_by":"auto","created_at":"2020-10-19 14:41:26","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":939153,"visible":true,"origin":"","legend":"Curative and protective effects of compound 4g on the bacterial leaf blight of rice","description":"","filename":"4.PNG","url":"https://assets-eu.researchsquare.com/files/rs-92183/v1/fd754c59eeb4cb0addb9025e.PNG"},{"id":3060164,"identity":"4ae0ac14-ef77-4d84-a52f-1518755441a8","added_by":"auto","created_at":"2020-10-19 14:41:27","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":292157,"visible":true,"origin":"","legend":"SEM images for Xoo after incubated in different concentration of compound 4c","description":"","filename":"5.PNG","url":"https://assets-eu.researchsquare.com/files/rs-92183/v1/0cbb883e7ac4772bb7ecd9b4.PNG"},{"id":3060166,"identity":"aa1b2007-d320-4747-99ae-694d2923d1b2","added_by":"auto","created_at":"2020-10-19 14:41:27","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":40783,"visible":true,"origin":"","legend":"Synthetic route to title compounds 4a-4x","description":"","filename":"scheme1.PNG","url":"https://assets-eu.researchsquare.com/files/rs-92183/v1/155f1a80f3e3906c789465cd.PNG"},{"id":13604238,"identity":"35e6fa63-9c8d-4b47-9789-524351587241","added_by":"auto","created_at":"2021-09-17 05:59:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2057700,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-92183/v1/902cfae8-17c7-423e-91a6-67e330f85333.pdf"},{"id":3060163,"identity":"8d1c2918-5c9e-490b-bdf6-6f6e4814bf33","added_by":"auto","created_at":"2020-10-19 14:41:26","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":3041280,"visible":true,"origin":"","legend":"","description":"","filename":"SupportingInformation.doc","url":"https://assets-eu.researchsquare.com/files/rs-92183/v1/2bd9c92337a3a2d077c8e37c.doc"},{"id":3060165,"identity":"7439897d-986a-4f21-8eab-b8bdd50f6071","added_by":"auto","created_at":"2020-10-19 14:41:27","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":193329,"visible":true,"origin":"","legend":"","description":"","filename":"checkcif.pdf","url":"https://assets-eu.researchsquare.com/files/rs-92183/v1/aab465e74a852c20aaf5b73d.pdf"}],"financialInterests":"","formattedTitle":"Design, Synthesis and Antibacterial Activity of Novel Pyrimidine-Containing 4H-Chromen-4-one Derivatives","fulltext":[{"header":"Background","content":" \u003cp\u003eOne of the main causes of plant diseases is bacterial infection, which causes a large amount of losses to the yield of economic crops every year. Such as, the citrus canker, tobacco bacterial wilt and rice bacterial leaf blight were caused by \u003cem\u003eXanthomonas axonopodis pv. citri\u003c/em\u003e (\u003cem\u003eXac\u003c/em\u003e), \u003cem\u003eRalstonia solanacearum\u003c/em\u003e (\u003cem\u003eRs\u003c/em\u003e) \u003cem\u003eand Xanthomonas oryzae pv. oryzae\u003c/em\u003e (\u003cem\u003eXoo\u003c/em\u003e), respectively [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It was very serious and hard to manage effectively in agricultural production. Therefore, to protect crops from bacterial infection, the agrochemical (bismerthiazol, thiodiazole-copper and azoxy strobin) were used to prevent bacterial infection [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], but prolonged and abuse of traditional chemical pesticides not only enhances the resistance of the bacterial but also harmful to the environment and human health [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. So, exploring novel highly-efficient, broad-spectrum and environmentally benign antibacterial agents is still an arduous task in pesticide science.\u003c/p\u003e \u003cp\u003e3,5,7-Trihydroxy-2-(3,4,5-trihydroxyphen-yl)-4\u003cem\u003eH\u003c/em\u003e-chromen-4-one (called \"myricetin\") (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA) belongs to a class of natural product that widely found in fruits, vegetables, and herbs, which has attracted more and more researchers due to the unique chemical structure and diverse biological activities [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Pharmacological research shows that myricetin and its derivatives present antiviral [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], antibacterial [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], antioxidation [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], anticancer [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], anti-inflammatory [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] and other biological properties, but most of them are limited to the field of medicine and have few applications in agriculture. In previous work, myricetin was took as the lead compound and active fragments were introduced, a mass of myricetin derivatives with significant biological activity have been discovered. In 2017, Zhong described myricetin derivatives containing 1,3,4 thiadiazole structure, which displaied good inhibitory effect on phytopathogenic bacteria [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Recently, Jiang reported a series of dithiocarbamate-containing 4\u003cem\u003eH\u003c/em\u003e-chromen-4-one derivatives with good in vitro antibacterial activity against \u003cem\u003eXac\u003c/em\u003e and \u003cem\u003eXoo\u003c/em\u003e, with an EC\u003csub\u003e50\u003c/sub\u003e values are 0.11\u0026nbsp;\u0026micro;g/mL and 1.58\u0026nbsp;\u0026micro;g/mL, respectively, which were far better than commercial agents bismerthiazol and thiodiazole copper [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePyrimidine is an important class of heterocyclic compounds with wide applications in medicine and pesticides research due to their remarkable biological and pharmacological properties, such as antibacterial [\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], antiviral [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], insecticide [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], anticancer [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], antimalaria[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], herbicida [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] and other biological activities[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In 2019, Zhang reported a series of derivatives containing pyrimidine ethers were synthesized, which have a good control effect on cucumber downy mildew [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Recently, Bai described some pyrimidine derivatives with signifcantly inhibitory effciencies against Gram-positive bacteria, Gram-negative bacteria and the fungus \u003cem\u003eCandida albicans\u003c/em\u003e [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo develop novel, highly efficient and environment friendly bactericides, we introduced the pyrimidine moiety into 4\u003cem\u003eH\u003c/em\u003e-chromen-4-one, and a variety of pyrimidine-containing 4\u003cem\u003eH\u003c/em\u003e-chromen-4-\u003c/p\u003e \u003cp\u003eone derivatives were synthesized and their antibactiral activity were evaluated.\u003c/p\u003e "},{"header":"Results And Discussion","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eChemistry\u003c/h2\u003e \u003cp\u003eThe structure of title compounds \u003cb\u003e4a-4x\u003c/b\u003e were characterized by \u003csup\u003e1\u003c/sup\u003eH NMR, \u003csup\u003e13\u003c/sup\u003eC NMR, \u003csup\u003e19\u003c/sup\u003eF NMR and HRMS. In \u003csup\u003e1\u003c/sup\u003eH NMR spectra, multiplet signals at δ 8.00\u0026ndash;6.50\u0026nbsp;ppm show the presence of protons in aromatic nucleuses, and a singlet at δ 4.00-3.70\u0026nbsp;ppm reveals the presence of -OCH\u003csub\u003e3\u003c/sub\u003e group, the -O-CH\u003csub\u003e2\u003c/sub\u003e- and -S-CH\u003csub\u003e2\u003c/sub\u003e- characteristic groups between the 4\u003cem\u003eH\u003c/em\u003e-chromen-4-one skeleton and the substituted pyrimidine were observed at 4.10\u0026ndash;3.37\u0026nbsp;ppm. The chemical shifts at 172.57\u0026ndash;160.77\u0026nbsp;ppm 109.12\u0026ndash;106.14\u0026nbsp;ppm, 27.80\u0026ndash;32.12\u0026nbsp;ppm in the \u003csup\u003e13\u003c/sup\u003eC NMR spectra confirmed the existence of C\u0026thinsp;=\u0026thinsp;O, -CN and -CH\u003csub\u003e2\u003c/sub\u003e- groups, respectively. The HRMS spectra of title compounds show absorption signals of [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e ions that is consistent with their molecular weight.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eX-ray crystal structure of title compounds 4\u0026nbsp;g\u003c/h2\u003e \u003cp\u003eTo further confirm the structures of title compounds, compound \u003cb\u003e4\u0026nbsp;g\u003c/b\u003e was successfully cultured a single crystal and studied by single-crystal X-ray analysis as a representative example. The tested single crystal was crystallized from DMSO and acetone mixture solution containing compound \u003cb\u003e4\u0026nbsp;g\u003c/b\u003e. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e3\u003c/span\u003eB, C00T-H\u0026hellip;O007 and O00R\u0026hellip;H-C00R are two important intramolecular hydrogen bonds that combine with 4\u003cem\u003eH\u003c/em\u003e-chromen-4-one and pyrimidine heterocycle fragments to construct the main molecular scaffold of target compound \u003cb\u003e4\u0026nbsp;g\u003c/b\u003e. Besides, as presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e3\u003c/span\u003eC, four intermolecular hydrogen bonds (O008\u0026hellip;H\u0026ndash;C011, C00J\u0026hellip;H-C00L, C00J\u0026hellip;C00L-H, C011\u0026ndash;H\u0026hellip;O008) between neighboring molecules are primary forces for establishing the three-dimensional structure of target compound \u003cb\u003e4\u0026nbsp;g\u003c/b\u003e. crystallographic data listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The deposition number is CCDC 2022970.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCrystal data of title compound 4\u0026nbsp;g.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCrystal Data\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC\u003csub\u003e34\u003c/sub\u003e H\u003csub\u003e30\u003c/sub\u003e BrN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003e S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eColourless/ block\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMr\u0026thinsp;=\u0026thinsp;736.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eρ\u0026thinsp;=\u0026thinsp;1.430\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003etriclinic / P-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eZ\u0026thinsp;=\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ea\u0026thinsp;=\u0026thinsp;12.025(3) [\u0026Aring;]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eα\u0026thinsp;=\u0026thinsp;103.276(15) [\u0026deg;]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eb\u0026thinsp;=\u0026thinsp;12.509(4 ) [\u0026Aring;]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ\u0026thinsp;=\u0026thinsp;112.727(15) [\u0026deg;]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ec\u0026thinsp;=\u0026thinsp;14.791(4) [\u0026Aring;]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eγ\u0026thinsp;=\u0026thinsp;102.837(17) [\u0026deg;]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF(000)\u0026thinsp;=\u0026thinsp;832\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eV\u0026thinsp;=\u0026thinsp;1873.79(9) [\u0026Aring;\u003csup\u003e3\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eData Collection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT \u003csub\u003emin\u003c/sub\u003e=0.310 T \u003csub\u003emax\u003c/sub\u003e=0.752\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsorption coefficient: 2.537 [mm-1]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3580 Independent reflections\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eθ\u003csub\u003emin\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;3.870\u0026deg;, θ\u003csub\u003emax\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;64.332\u0026deg;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18889 Reflections collected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-13\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;h\u0026lt;=13, -14\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;k\u0026lt;=14, -17\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;l\u0026lt;=16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRefinement\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e438 parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eR indices (all data) R1\u0026thinsp;=\u0026thinsp;0.1186, wR2\u0026thinsp;=\u0026thinsp;2964\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGoodness-of-fit: 1.090\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eR indices [I\u0026thinsp;\u0026gt;\u0026thinsp;2r(I)] R1\u0026thinsp;=\u0026thinsp;0.0835, wR2\u0026thinsp;=\u0026thinsp;2591\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔρ\u003csub\u003emax\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.426 e\u0026Aring;\u003csup\u003e\u0026minus;3\u003c/sup\u003e, Δρ\u003csub\u003emin\u003c/sub\u003e= -0.750 e\u0026Aring;\u003csup\u003e\u0026minus;3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eAntibacterial activity of the title compounds against Xac,Xoo and Rs in vitro\u003c/h2\u003e \u003cp\u003eThe \u003cem\u003ein vitro\u003c/em\u003e antibacterial activities of title compounds \u003cb\u003e4a\u003c/b\u003e-\u003cb\u003e4x\u003c/b\u003e against \u003cem\u003eXac\u003c/em\u003e, \u003cem\u003eXoo\u003c/em\u003e and \u003cem\u003eRs\u003c/em\u003e were determined using turbidimeter tests [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. and the bismerthiazol, thiadiazole copper, and myricetin were tested as the control. Preliminary bioassays results in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e indicated that Some compounds with good antibacterial activity against \u003cem\u003eXac\u003c/em\u003e, \u003cem\u003eXoo\u003c/em\u003e and \u003cem\u003eRs\u003c/em\u003e, Among them, compounds \u003cb\u003e4b\u003c/b\u003e, \u003cb\u003e4c\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;h\u003c/b\u003e and \u003cb\u003e4o\u003c/b\u003e against \u003cem\u003eXac\u003c/em\u003e at 100 and 50\u0026nbsp;\u0026micro;g/mL with the inhibition rates of 80.4 and 51.4%, 91.3 and 69.0%, 85.3 and 51.4%, 83.2 and 50.5%, respectively, which were better than that of BT (64.6 and 43.4%), TC(55.0 and 34.6%) and myricetin(44.9 and 27.5%). The inhibitory rates of compounds \u003cb\u003e4c\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;h\u003c/b\u003e, \u003cb\u003e4n\u003c/b\u003e and \u003cb\u003e4p\u003c/b\u003e indicated against \u003cem\u003eXoo\u003c/em\u003e at 100\u0026nbsp;\u0026micro;g/mL were 89.7, 81.2, 78.3 and 80.7%, respectively, which were superior to that of BT (63.9%), TC (49.5%) and myricetin (44.0%). Note that the inhibition rates of \u003cb\u003e4c\u003c/b\u003e, \u003cb\u003e4d\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;h\u003c/b\u003e, \u003cb\u003e4n\u003c/b\u003e, \u003cb\u003e4o, 4p\u003c/b\u003e and \u003cb\u003e4x\u003c/b\u003e against \u003cem\u003eXoo\u003c/em\u003e at 50\u0026nbsp;\u0026micro;g/mL were 72.1, 41.7, 56.0, 54.7, 49.5, 56.0 and 45.6%, respectively, which were superior to those of bismerthiazol (44.5%), thiadiazole copper (36.5%) and myricetin (33.3%). Furthermore, \u003cb\u003e4c\u003c/b\u003e, \u003cb\u003e4d\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;h\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;k 4\u0026nbsp;l\u003c/b\u003e, \u003cb\u003e4o\u003c/b\u003e and \u003cb\u003e4w\u003c/b\u003e have fine antibacterial activity against \u003cem\u003eRs\u003c/em\u003e at 100\u0026nbsp;\u0026micro;g/mL with the inhibition rates of 90.9, 83.9, 92.7, 88.7, 83.2, 90.4 and 80.6%, which were better than those of BT (71.7%), TC (60.1%) and myricetin (50.7%). Similarly, the percentage inhibition of \u003cb\u003e4c\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;h\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;k\u003c/b\u003e, \u003cb\u003e4o\u003c/b\u003e and \u003cb\u003e4w\u003c/b\u003e against Rs at 50\u0026nbsp;\u0026micro;g/mL were 72.5, 76.2, 66.3, 71.9 and 59.0%, which exceeded BT (52.4%), TC (41.3%) and myricetin (29.6%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntibacterial activities of title compounds (4a-4x) against Xac, Xoo and Rs in vitro\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCompd.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e\u003cem\u003eXac\u003c/em\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e\u003cem\u003eXoo\u003c/em\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e\u003cem\u003eRs\u003c/em\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100\u0026nbsp;\u0026micro;g/mL\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50\u0026nbsp;\u0026micro;g/mL\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e100\u0026nbsp;\u0026micro;g/mL\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e50\u0026nbsp;\u0026micro;g/mL\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e100\u0026nbsp;\u0026micro;g/mL\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e50\u0026nbsp;\u0026micro;g/mL\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4a\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e50.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e39.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4b\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3-CH\u003csub\u003e3\u003c/sub\u003e-Ph\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e32.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4c\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e-Ph\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e89.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e72.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e90.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e72.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e 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colname=\"c7\"\u003e \u003cp\u003e24.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e34.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e24.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4f\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-Cl-Ph\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e35.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e27.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4\u0026nbsp;g\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-Br-Ph\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e 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align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e88.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e66.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4\u0026nbsp;l\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epyridin-4-yl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e 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colname=\"c4\"\u003e \u003cp\u003e47.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e28.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e51.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e25.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e 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\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e56.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e14.\u0026plusmn;5.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4q\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3-Cl-Ph\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e34.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e48.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e35.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4r\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-Cl-Ph\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e62.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e39.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4\u0026nbsp;s\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3-Br-Ph\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e22.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e12.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4t\u003c/b\u003e\u003c/p\u003e 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\u003cp\u003e53.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e39.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4v\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-F-Ph\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e27.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e57.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e37.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4w\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003efuran-2-yl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e28.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e80.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e59.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4x\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epyridin-4-yl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e68.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e45.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e61.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e33.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMy\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e50.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e29.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTC\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e49.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e36.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e60.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e41.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBT\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e63.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e44.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e71.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e52.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003ea Average of three replicates.\u003c/p\u003e \u003cp\u003eb The lead compound of myricetin.\u003c/p\u003e \u003cp\u003ec The commercial bactericides bismerthiazol (BT) and thiediazole copper (TC).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBased on the preliminary bioassays results in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the EC\u003csub\u003e50\u003c/sub\u003e values of some target compounds against \u003cem\u003eXac\u003c/em\u003e, \u003cem\u003eXoo\u003c/em\u003e and \u003cem\u003eRs\u003c/em\u003e, were indicated in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, that compounds \u003cb\u003e4b\u003c/b\u003e, \u003cb\u003e4c\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;h\u003c/b\u003e and \u003cb\u003e4o\u003c/b\u003e exhibited fine antibacterial activities against \u003cem\u003eXac\u003c/em\u003e, with EC\u003csub\u003e50\u003c/sub\u003e values of 30.8, 15.5, 28.2, and 29.2\u0026nbsp;\u0026micro;g/mL, respectively, which exceeded BT (51.7\u0026nbsp;\u0026micro;g/mL), and TC (77.9\u0026nbsp;\u0026micro;g/mL). \u003cb\u003e4c\u003c/b\u003e, \u003cb\u003e4d\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;h\u003c/b\u003e, \u003cb\u003e4n\u003c/b\u003e and \u003cb\u003e4p\u003c/b\u003e demonstrated good inhibitory effects against \u003cem\u003eXoo\u003c/em\u003e with an EC\u003csub\u003e50\u003c/sub\u003e value of 14.9, 30.6, 23.7, 28.6 and 24.8\u0026nbsp;\u0026micro;g/mL, which were better than that of BT (70.1\u0026nbsp;\u0026micro;g/mL) and TC (95.8\u0026nbsp;\u0026micro;g/mL). Compounds \u003cb\u003e4c\u003c/b\u003e, \u003cb\u003e4d\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;h\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;k\u003c/b\u003e, \u003cb\u003e4\u0026nbsp;l\u003c/b\u003e and \u003cb\u003e4o\u003c/b\u003e have better antibacterial activity against Rs with the EC\u003csub\u003e50\u003c/sub\u003e values of 16.0, 23.1, 14.7, 17.5, 24.4, 16.0, and 29.4\u0026nbsp;\u0026micro;g/mL, respectively, which were superior to that of BT (52.8\u0026nbsp;\u0026micro;g/mL) and TC (72.1\u0026nbsp;\u0026micro;g/mL).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEC50 values of the title compounds against Xac, Xoo and Rs in vitroa\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTested bacterial\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCompds.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eToxic regression equation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003er\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEC\u003csub\u003e50\u003c/sub\u003e/(\u0026micro;g/mL)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003eXac\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4b\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.5705 x\u0026thinsp;+\u0026thinsp;2.6602\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9826\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4c\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.9107 x\u0026thinsp;+\u0026thinsp;2.7256\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9912\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4d\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.5736 x\u0026thinsp;+\u0026thinsp;2.5280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9825\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4\u0026nbsp;h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.7100 x\u0026thinsp;+\u0026thinsp;2.5176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9809\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4j\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.4978 x\u0026thinsp;+\u0026thinsp;2.6114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9873\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.6002 x\u0026thinsp;+\u0026thinsp;2.5541\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9947\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4o\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.7781 x\u0026thinsp;+\u0026thinsp;2.3894\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9811\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBT\u003c/b\u003e \u003csup\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ec\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.3743 x\u0026thinsp;+\u0026thinsp;2.6450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTC\u003c/b\u003e \u003csup\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ec\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.3153 x\u0026thinsp;+\u0026thinsp;2.5117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9822\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e77.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cem\u003eXoo\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4c\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.4639 x\u0026thinsp;+\u0026thinsp;3.2826\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9906\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4d\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.2237 x\u0026thinsp;+\u0026thinsp;3.1804\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9693\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4\u0026nbsp;h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.4072 x\u0026thinsp;+\u0026thinsp;3.0639\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9961\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4\u0026nbsp;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.2358 x\u0026thinsp;+\u0026thinsp;3.1996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9773\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4o\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.2425 x\u0026thinsp;+\u0026thinsp;3.1428\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9892\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4p\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.3657 x\u0026thinsp;+\u0026thinsp;3.0943\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9978\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBT \u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.3199 x\u0026thinsp;+\u0026thinsp;2.5633\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTC \u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.0632 x\u0026thinsp;+\u0026thinsp;2.8928\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9796\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003e\u003cem\u003eRS\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4c\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.6321 x\u0026thinsp;+\u0026thinsp;3.0312\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9929\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4d\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.4199 x\u0026thinsp;+\u0026thinsp;3.0625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9780\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4\u0026nbsp;h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.6908 x\u0026thinsp;+\u0026thinsp;3.0236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9969\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4\u0026nbsp;k\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.4931 x\u0026thinsp;+\u0026thinsp;3.1422\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9857\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4\u0026nbsp;l\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.4276 x\u0026thinsp;+\u0026thinsp;3.0175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9801\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4o\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.5422 x\u0026thinsp;+\u0026thinsp;3.1423\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9926\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4w\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.4597 x\u0026thinsp;+\u0026thinsp;2.8546\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBT\u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.4267 x\u0026thinsp;+\u0026thinsp;2.5425\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9543\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTC\u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.2906 x\u0026thinsp;+\u0026thinsp;2.5962\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9821\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Average of three replicates. \u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003eThe commercial agricultural antibacterial agents bismerthiazol (BT) and thiodiazole-copper (TC) were used as control agents.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eStructure\u0026ndash;activity relationship analysis of the antibacterial activities.\u003c/span\u003e \u003c/p\u003e \u003cp\u003eAs indicated in Tables\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, most of target compounds showed significant antibacterial activities against \u003cem\u003eXac\u003c/em\u003e, \u003cem\u003eXoo\u003c/em\u003e and \u003cem\u003eRs\u003c/em\u003e, the R groups had significant impact on the antibacterial activity, for example, \u003cb\u003e4c\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;3, R\u0026thinsp;=\u0026thinsp;4-CH\u003csub\u003e3\u003c/sub\u003e-Ph), \u003cb\u003e4\u0026nbsp;h\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;3,R\u0026thinsp;=\u0026thinsp;3-F-Ph), \u003cb\u003e4o\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;4, R\u0026thinsp;=\u0026thinsp;4-CH\u003csub\u003e3\u003c/sub\u003e-Ph) demonstrated a fine inhibitory effect against \u003cem\u003eXac\u003c/em\u003e with the EC\u003csub\u003e50\u003c/sub\u003e values of 15.5, 28.2 and 29.3\u0026nbsp;\u0026micro;g/mL, which were better than those of BT (51.7\u0026nbsp;\u0026micro;g/mL), andTC (77.9\u0026nbsp;\u003cem\u003e\u0026micro;g\u003c/em\u003e/mL) and other substituents. Compounds \u003cb\u003e4c\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;3, R\u0026thinsp;=\u0026thinsp;4-CH\u003csub\u003e3\u003c/sub\u003e-Ph), \u003cb\u003e4d\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;3, R\u0026thinsp;=\u0026thinsp;4-OCH\u003csub\u003e3\u003c/sub\u003e-Ph) and \u003cb\u003e4p\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;4, R\u0026thinsp;\u003cb\u003e=\u003c/b\u003e\u0026thinsp;4-OCH\u003csub\u003e3\u003c/sub\u003e-Ph) demonstrated good inhibitory effects against \u003cem\u003eXoo\u003c/em\u003e with an EC\u003csub\u003e50\u003c/sub\u003e value of 14.9, 23.7 and 24.8\u0026nbsp;\u0026micro;g/mL, which were better than that of BT (70.1\u0026nbsp;\u0026micro;g/mL) and TC (95.8\u0026nbsp;\u0026micro;g/mL). The presence of donor electron groups and heterocycles may effectively enhance the antibacterial activity against \u003cem\u003eRs\u003c/em\u003e, such as compounds \u003cb\u003e4c\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;3, R\u0026thinsp;=\u0026thinsp;4-CH\u003csub\u003e3\u003c/sub\u003e-Ph), \u003cb\u003e4d (n\u0026thinsp;=\u0026thinsp;3\u003c/b\u003e, R\u0026thinsp;=\u0026thinsp;4-OCH\u003csub\u003e3\u003c/sub\u003e-Ph), \u003cb\u003e4\u0026nbsp;k\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;3, R\u0026thinsp;=\u0026thinsp;furan), \u003cb\u003e4\u0026nbsp;l\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;3, R\u0026thinsp;=\u0026thinsp;pyridyl) and \u003cb\u003e4o\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;4, R\u0026thinsp;=\u0026thinsp;4-CH\u003csub\u003e3\u003c/sub\u003e-Ph) have better antibacterial activity against \u003cem\u003eRs\u003c/em\u003e with the EC\u003csub\u003e50\u003c/sub\u003e values of 16.0, 23.1, 17.5, 24.4 and 16.0\u0026nbsp;\u0026micro;g/mL, respectively, which were superior to that of BT (52.8\u0026nbsp;\u0026micro;g/mL) and TC (72.1\u0026nbsp;\u0026micro;g/mL). From this analysis, when n\u0026thinsp;=\u0026thinsp;3, R is 4-CH\u003csub\u003e3\u003c/sub\u003e-Ph, 4-CH\u003csub\u003e3\u003c/sub\u003eO-Ph, 3-F-Ph, the bioactivity of compounds are higher than that of n\u0026thinsp;=\u0026thinsp;4, R is 4-CH\u003csub\u003e3\u003c/sub\u003e-Ph, 4-CH\u003csub\u003e3\u003c/sub\u003eO-Ph, 3-F-Ph, the activity of the para-substituted by -CH\u003csub\u003e3\u003c/sub\u003e, -OCH\u003csub\u003e3\u003c/sub\u003e and other group on the benzene is greater than the meta-substituted. Meanwhile, R was substituted with 3-F-Ph groups, the corresponding compound exhibit remarkable antibacterial activities against \u003cem\u003eXac\u003c/em\u003e, \u003cem\u003eXoo\u003c/em\u003e and \u003cem\u003eRs\u003c/em\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eIn vivo bioactivity of 4c against rice bacterial leaf blight\u003c/h2\u003e \u003cp\u003eThe experiments of \u003cb\u003e4c\u003c/b\u003e against rice bacterial leaf blight was determined using a leaf-cutting method. Shown in Table\u0026nbsp;4 and Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003e, when the concentration of compound \u003cb\u003e4c\u003c/b\u003e was 200\u0026nbsp;\u0026micro;g.mL\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, the curative activity against bacterial blight of rice was 42.4%. This result was better than that of BT (35.2%) and TC (30.8%). Furthermore, compound \u003cb\u003e4c\u003c/b\u003e demonstrated excellent protection activity against bacterial blight of rice with the percentage inhibition of 49.2%, which was superior to BT (39.1%) and TC (27.3%). These results suggests that compound \u003cb\u003e4c\u003c/b\u003e effectively prevents the infection of Xanthomonas oryzae of rice.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eScanning electron microscopy (SEM) studies\u003c/h2\u003e \u003cp\u003eThe mechanism of compound against RS and Xoo were analyzed by SEM [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e5\u003c/span\u003e, the surface morphology of \u003cem\u003eXoo\u003c/em\u003e were smooth and remains intact without compound to treatment, (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). When the bacteria was treated with compound \u003cb\u003e4c\u003c/b\u003e at concentration of 50\u0026nbsp;ppm, bacteria cell membrane began to appear different degrees wrinkled (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e5\u003c/span\u003eB). as the concentration of compound increased to 100\u0026nbsp;ppm, the bacterial cell membrane showed invagination and rupture(Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e5\u003c/span\u003eC). Therefore, that compound \u003cb\u003e4c\u003c/b\u003e destroyed the cell membrane structure, to achieve the purpose of antibacterial.\u003c/p\u003e \u003c/div\u003e "},{"header":"Methods And Materials","content":" \u003cp\u003e \u003cem\u003eChemistry\u003c/em\u003e \u003c/p\u003e \u003cp\u003eAll solvents and reagents were purchased from Shanghai Titan Scientific Co., Ltd, and were analytical grade or chemically pure. The melting point of all compounds (\u003cb\u003e4a-4x\u003c/b\u003e) was determined by the X-4B melting point apparatus ((Beijing Tech Instrument Co, Beijing. China). \u003csup\u003e1\u003c/sup\u003eH NMR, \u003csup\u003e13\u003c/sup\u003eC NMR and \u003csup\u003e19\u003c/sup\u003eF NMR were obtained on Bruker Ascend-400 spectrometer (Bruker Optics, Germany) Tetramethylsilane (TMS) as internal standard and DMSO was used as solvent; Mass spectral studies were performed on a quadrupole electrostatic field orbitrap mass spectrograph (Thermo Scientific, USA). The synthetic route of pyrimidine-containing 4\u003cem\u003eH\u003c/em\u003e-Chromen-4-one derivatives was shown in Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Intermediates \u003cb\u003e1\u003c/b\u003e were prepared according to the reported methods. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e \u003cem\u003eGeneral synthesis procedure for intermediate\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e1.\u003c/span\u003e\u003c/p\u003e \u003cp\u003eBased on the previous reported method [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], the ethyl cyanoacetate (5\u0026nbsp;mmol), substituted aromatic aldehyde (5\u0026nbsp;mmol), thiourea (5\u0026nbsp;mmol) and anhydrous K\u003csub\u003e2\u003c/sub\u003eCO\u003csub\u003e3\u003c/sub\u003e (7.5\u0026nbsp;mmol) were added in ethanol (50\u0026nbsp;mL) then refluxed for about 4\u003cb\u003e\u0026ndash;\u003c/b\u003e6\u0026nbsp;h, after the reaction was completed (monitoring the reaction by TLC), mixture was cooled to room temperature and diluted with ice water, a large amount of solids precipitated as the pH was adjusted with glacial acetic acid to weak acidity, solids were filtered and dried with suction, recrystallized with absolute ethanol to obtain Intermediate \u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cem\u003eGeneral synthesis procedures for intermediate\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/p\u003e \u003cp\u003eMyricetin as raw material, iodomethane as the methylation reagent and anhydrous K\u003csub\u003e2\u003c/sub\u003eCO\u003csub\u003e3\u003c/sub\u003e, heated to reflux in DMF and then extracted with methylene chloride, deglycosylation with concentrated hydrochloric acid under reflux in ethanol to prepare 3-hydroxy-3',4',5',5,7- pentamethoxymyricetin (Intermediate \u003cb\u003e2\u003c/b\u003e).\u003c/p\u003e \u003cp\u003e \u003cem\u003eGeneral synthesis procedures for intermediate\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/p\u003e \u003cp\u003eIntermediate \u003cb\u003e2\u003c/b\u003e (2\u0026nbsp;mmol) and K\u003csub\u003e2\u003c/sub\u003eCO\u003csub\u003e3\u003c/sub\u003e (3\u0026nbsp;mmol) are dissolved in certain amount of \u003cem\u003eN\u003c/em\u003e,\u003cem\u003eN\u003c/em\u003e-dimethylformamide (DMF). After the solution had been stirred at room temperature for 0.5\u003cb\u003e\u0026ndash;\u003c/b\u003e1\u0026nbsp;h, the different dibromoalkane (2\u0026nbsp;mmol) was added and reaction system continued at room temperature for 10\u0026nbsp;h. Mixture was dispersed in 50\u0026nbsp;mL ice water when reaction was completed (reaction was monitored by TLC) so a white solid was precipitated, sample was passed through a suction filter to remove the liquid, solid was continuously stirred in a mixed solution of 30\u0026nbsp;mL petroleum ether and ethyl acetate for 3\u0026ndash;4 hours, then filtered and dried under reduced pressure to obtain Intermediate \u003cb\u003e3\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cem\u003eGeneral synthesis procedures for title compounds\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e4\u003c/span\u003e\u003c/p\u003e \u003cp\u003eA solution of intermediates \u003cb\u003e1\u003c/b\u003e (3\u0026nbsp;mmol), intermediates \u003cb\u003e3\u003c/b\u003e (3\u0026nbsp;mmol) and K\u003csub\u003e2\u003c/sub\u003eCO\u003csub\u003e3\u003c/sub\u003e (4.5\u0026nbsp;mmol) in DMF (40\u0026nbsp;mL) was stirred under reflux for 4\u0026ndash;5\u0026nbsp;h, after reaction was completed (reaction was monitored by TLC), the mixture was cooled to room temperature then poured into 80\u0026nbsp;mL ice water and extracted with ethyl acetate (3\u0026thinsp;\u0026times;\u0026thinsp;30\u0026nbsp;mL), organic layer was washed with 5% hydrochloric acid solution, saturated NaHCO\u003csub\u003e3\u003c/sub\u003e aqueous solution, saturated NaCl solution successively and dried with anhydrous Na\u003csub\u003e2\u003c/sub\u003eSO\u003csub\u003e4\u003c/sub\u003e, solvent was removed under vacuum and crude product was separated by column chromatography with petroleum ether/ethyl acetate (\u003cem\u003eV:V\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1:1) to obtain the title compound \u003cb\u003e4a\u003c/b\u003e. Based on the similar method, the title compounds \u003cb\u003e4b\u003c/b\u003e-\u003cb\u003e4x\u003c/b\u003e were prepared.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4a)\u003c/span\u003e: white solid, m.p.\u0026nbsp;144.3-145.8\u0026nbsp;\u0026deg;C; yield: 41.3%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.94 (d, J\u0026thinsp;=\u0026thinsp;7.3\u0026nbsp;Hz, 2H, Ph-H), 7.56 (d, J\u0026thinsp;=\u0026thinsp;7.0\u0026nbsp;Hz, 1H, Ph-H), 7.50 (t, J\u0026thinsp;=\u0026thinsp;7.2\u0026nbsp;Hz, 2H, Ph-H), 7.34 (s, 2H, Ph-H), 6.84 (s, 1H, Ph-H), 6.50 (s, 1H, Ph-H), 4.03 (s, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.85 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.81 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.72 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.39 (s, 2H, -CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.12 (d, J\u0026thinsp;=\u0026thinsp;5.7\u0026nbsp;Hz, 2H, -CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.57, 164.27, 160.77, 158.65, 153.17, 152.21, 140.16, 139.89, 132.18, 129.08, 128.99, 125.94, 116.45, 108.88, 106.12, 96.41, 93.60, 93.39, 70.50, 60.63, 56.57, 56.49, 30.06, 27.80; HRMS calcd for C\u003csub\u003e34\u003c/sub\u003eH\u003csub\u003e31\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 658.1854, found 658.1851.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-4-(m-tolyl)-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4b)\u003c/span\u003e: white solid, m.p.\u0026nbsp;231.6-232.8\u0026nbsp;\u0026deg;C; yield: 67.2%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.71 (s, 2H, Ph-H), 7.37 (d, J\u0026thinsp;=\u0026thinsp;6.9\u0026nbsp;Hz, 2H, Ph-H), 7.34 (s, 2H, Ph-H), 6.85 (d, J\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.50 (d, J\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 4.02 (t, J\u0026thinsp;=\u0026thinsp;5.8\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.85 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.80 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.72 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.34 (s, 2H, O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.31 (s, 3H, Ph-CH\u003csub\u003e3\u003c/sub\u003e), 2.15\u0026ndash;2.04 (m, 2H, -CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.56, 167.64, 164.26, 160.75, 158.65, 153.16, 152.18, 140.20, 139.82, 138.29, 132.64, 129.49, 128.85, 126.31, 125.94, 108.85, 106.03, 96.41, 93.57, 70.55, 60.63, 56.53, 56.45, 30.17, 27.74, 21.32; HRMS calcd for C\u003csub\u003e35\u003c/sub\u003eH\u003csub\u003e33\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 672.2010, found 672.1999.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-4-(p-tolyl)-1,6-dihydropyrimidine-5-carbonitrile (\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e4c\u003c/span\u003e \u003cem\u003e)\u003c/em\u003e: White solid, m.p.\u0026nbsp;201.8-203.6\u0026nbsp;\u0026deg;C; yield: 30.3%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.85 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.1\u0026nbsp;Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 7.27 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.1\u0026nbsp;Hz, 2H, Ph-H), 6.85 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.1\u0026nbsp;Hz, 1H, Ph-H), 6.51 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.1\u0026nbsp;Hz, 1H, Ph-H), 4.03 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.9\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.91 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.86 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.82 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.72 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.36 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.5\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.34 (s, 3H, Ph-CH\u003csub\u003e3\u003c/sub\u003e), 2.12 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;12.8, 6.3\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.57, 166.16, 164.28, 160.78, 158.66, 153.18, 152.18, 142.51, 140.17, 139.90, 132.85, 129.56, 129.18, 125.94, 116.59, 108.90, 106.11, 96.42, 93.61, 92.75, 70.53, 60.61, 56.77, 56.39, 55.39, 30.13, 27.78, 21.51; HRMS calcd for C\u003csub\u003e35\u003c/sub\u003eH\u003csub\u003e33\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 671.1932, found 671.1905.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e4d\u003c/span\u003e \u003cem\u003e)\u003c/em\u003e: white solid, m.p.\u0026nbsp;179.2-181.1\u0026nbsp;\u0026deg;C; yield: 32.5%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 8.01 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.8\u0026nbsp;Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 7.02 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.9\u0026nbsp;Hz, 2H, Ph-H), 6.84 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.50 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 4.04 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.9\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.91 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.86 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.81 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.80 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.72 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.39 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.9\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.17\u0026ndash;2.07 (m, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.57, 164.27, 162.66, 160.77, 158.65, 153.17, 152.14, 140.19, 139.90, 131.27, 125.93, 116.88, 114.42, 108.88, 106.09, 96.42, 93.60, 70.51, 60.62, 56.57, 56.52, 56.48, 55.88, 55.39, 30.16, 27.76; HRMS calcd for C\u003csub\u003e35\u003c/sub\u003eH\u003csub\u003e33\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e10\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 688.1959, found 688.1952.\u003c/p\u003e \u003cp\u003e \u003cem\u003e4-(3-chlorophenyl)-2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e4e\u003c/span\u003e \u003cem\u003e)\u003c/em\u003e: Brown solid, m.p.\u0026nbsp;119.6-121.9\u0026nbsp;\u0026deg;C; yield: 23.9%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.94\u0026ndash;7.84 (m, 2H, Ph-H), 7.62 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0\u0026nbsp;Hz, 1H, Ph-H), 7.53 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.9\u0026nbsp;Hz, 1H, Ph-H), 7.33 (s, 2H, Ph-H), 6.83 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.6\u0026nbsp;Hz, 1H, Ph-H), 6.50 (s, 1H, Ph-H), 4.02 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.5\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.85 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.81 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.72 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.35 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.3\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.13\u0026ndash;2.02 (m, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.58, 165.98, 164.24, 160.75, 158.64, 153.14, 152.19, 140.21, 139.85, 137.87, 133.66, 131.70, 130.91, 128.69, 127.77, 125.96, 108.87, 106.08, 96.39, 93.57, 70.49, 60.63, 56.56, 56.51, 56.47, 30.11, 27.76; HRMS calcd for C\u003csub\u003e34\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eClN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 692.1464, found 692.1455.\u003c/p\u003e \u003cp\u003e \u003cem\u003e4-(4-chlorophenyl)-2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e4f\u003c/span\u003e \u003cem\u003e)\u003c/em\u003e: White solid, m.p.\u0026nbsp;182.4-183.8\u0026nbsp;\u0026deg;C; yield: 41.7%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.93 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5\u0026nbsp;Hz, 2H, Ph-H), 7.55 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5\u0026nbsp;Hz, 2H, Ph-H), 7.36 (s, 2H, Ph-H), 6.84 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.0\u0026nbsp;Hz, 1H, Ph-H), 6.50 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.0\u0026nbsp;Hz, 1H, Ph-H), 4.03 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.0\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.91 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.87 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.83 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.73 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.28 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.9\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.14\u0026ndash;2.06 (m, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.59, 166.22, 164.26, 160.76, 158.65, 153.18, 152.15, 140.18, 139.89, 136.55, 135.01, 130.89, 129.03, 125.95, 108.89, 106.09, 96.42, 93.61, 70.60, 60.62, 56.59, 56.50, 30.29, 27.55; HRMS calcd for C\u003csub\u003e34\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eClN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 692.1640, found 692.1450.\u003c/p\u003e \u003cp\u003e \u003cem\u003e4-(4-bromophenyl)-2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e (\u003cb\u003e4\u0026nbsp;g\u003c/b\u003e): White solid, m.p.\u0026nbsp;183.2-185.1\u0026nbsp;\u0026deg;C; yield: 25.7%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.88 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5\u0026nbsp;Hz, 2H, Ph-H), 7.70 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5\u0026nbsp;Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 6.85 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.8\u0026nbsp;Hz, 1H, Ph-H), 6.51 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.7\u0026nbsp;Hz, 1H, Ph-H), 4.03 (s, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.91 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.87 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.83 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.73 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.37 (s, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.16\u0026ndash;2.06 (m, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-). \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.59, 166.41, 164.28, 160.76, 158.65, 153.18, 152.17, 140.14, 139.89, 134.84, 132.08, 131.16, 125.96, 116.36, 108.88, 106.07, 96.43, 93.52, 70.48, 60.63, 56.63, 56.50, 30.16, 27.74; HRMS calcd for C\u003csub\u003e34\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eBrN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 736.0959, found 736.0927.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-4-(3-fluorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e (\u003cb\u003e4\u0026nbsp;h\u003c/b\u003e): Brown solid, m.p.\u0026nbsp;204.6-206.4\u0026nbsp;\u0026deg;C; yield: 57.0%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.78 (d, J\u0026thinsp;=\u0026thinsp;7.8\u0026nbsp;Hz, 1H, Ph-H), 7.70 (d, J\u0026thinsp;=\u0026thinsp;9.8\u0026nbsp;Hz, 1H, Ph-H), 7.55 (dd, J\u0026thinsp;=\u0026thinsp;14.0, 8.0\u0026nbsp;Hz, 1H, Ph-H), 7.40 (td, J\u0026thinsp;=\u0026thinsp;8.5, 2.3\u0026nbsp;Hz, 1H, Ph-H), 7.34 (s, 2H, Ph-H), 6.83 (d, J\u0026thinsp;=\u0026thinsp;2.1\u0026nbsp;Hz, 1H, Ph-H), 6.49 (d, J\u0026thinsp;=\u0026thinsp;2.1\u0026nbsp;Hz, 1H, Ph-H), 4.02 (t, J\u0026thinsp;=\u0026thinsp;5.8\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.85 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.81 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.72 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.34 (d, J\u0026thinsp;=\u0026thinsp;6.8\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.16\u0026ndash;2.03 (m, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.59, 166.00, 164.24, 163.41, 160.98, 160.75, 158.64, 153.15, 152.19, 140.18, 139.85, 131.15, 131.07, 125.95, 125.28, 118.86, 118.66, 116.75, 115.94, 115.71, 108.87, 106.07, 96.39, 93.57, 70.52, 60.62, 56.55, 56.51, 56.46, 30.13, 27.72; \u003csup\u003e19\u003c/sup\u003eF NMR (376\u0026nbsp;MHz, DMSO\u003cem\u003e-d\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ -112.23 (d, J\u0026thinsp;=\u0026thinsp;6.1\u0026nbsp;Hz); HRMS calcd for C\u003csub\u003e34\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eFN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 676.1760, found 676.1755.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-4-(4-fluorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e (\u003cb\u003e4i\u003c/b\u003e): White solid, m.p.\u0026nbsp;197.5-199.4\u0026nbsp;\u0026deg;C; yield: 31.7%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 8.05 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.1, 5.6\u0026nbsp;Hz, 2H, Ph-H), 7.39\u0026ndash;7.30 (m, 4H, Ph-H), 6.84 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.3\u0026nbsp;Hz, 1H, Ph-H), 6.50 (s, 1H, Ph-H), 4.02 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.9\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.91 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.86 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.82 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.73 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.37 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.5\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.18\u0026ndash;2.06 (m, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.57, 166.40, 165.71, 164.25, 163.22, 160.72, 158.64, 153.16, 152.16, 140.13, 139.83, 131.99, 131.89, 125.92, 116.46, 116.25, 116.03, 108.85, 106.01, 96.40, 93.58, 93.21, 70.42, 60.61, 56.51, 56.46, 30.10, 27.72; \u003csup\u003e19\u003c/sup\u003eF NMR (376\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ -107.84; HRMS calcd for C\u003csub\u003e34\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eFN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 676.1760, found 676.1755.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-4-(thiophen-2-yl)-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4j)\u003c/span\u003e : Gray solid, m.p.\u0026nbsp;145.4-147.8\u0026nbsp;\u0026deg;C; yield: 50.6%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 8.22 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.8\u0026nbsp;Hz, 1H, thienyl-H), 7.94 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.0\u0026nbsp;Hz, 1H, thienyl-H), 7.36 (s, 2H, Ph-H), 7.31\u0026ndash;7.27 (m, 1H, thienyl -H), 6.82 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.1\u0026nbsp;Hz, 1H, Ph-H), 6.49 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.1\u0026nbsp;Hz, 1H, Ph-H), 4.07 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.0\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.85 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.73 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.30 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0\u0026nbsp;Hz, 2H -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.17\u0026ndash;2.09 (m, 2H -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.60, 164.24, 160.75, 158.95, 158.64, 153.16, 152.23, 140.33, 140.17, 139.87, 134.86, 131.58, 129.84, 125.97, 117.16, 108.88, 106.16, 96.40, 93.57, 88.04, 70.60, 60.64, 56.57, 56.51, 30.09, 27.86; HRMS calcd for C\u003csub\u003e33\u003c/sub\u003eH\u003csub\u003e28\u003c/sub\u003eN\u003csub\u003e4\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e[M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 664.1418, found 664.1411.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-4-(furan-2-yl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4\u0026nbsp;k)\u003c/span\u003e: Gray solid, m.p.\u0026nbsp;229.4-231.3\u0026nbsp;\u0026deg;C; yield: 60.3%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 8.09 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.8\u0026nbsp;Hz, 1H, furyl-H), 7.47 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.5\u0026nbsp;Hz, 1H, furyl-H), 7.36 (s, 2H, Ph-H), 6.83 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, furyl-H), 6.70 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.5, 1.7\u0026nbsp;Hz, 1H, Ph-H), 6.49 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 4.06 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.0\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.91 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.86 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.73 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.35 (s, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.15\u0026ndash;2.06 (m, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.59, 164.25, 160.77, 158.64, 154.94, 153.17, 152.21, 149.92, 148.42, 140.17, 139.91, 125.94, 118.62, 115.85, 113.63, 108.90, 106.14, 96.41, 93.58, 88.01, 70.64, 60.63, 56.57, 56.51, 55.39, 30.06, 27.81; HRMS calcd for C\u003csub\u003e32\u003c/sub\u003eH\u003csub\u003e29\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e10\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 648.1646, found 648.1638.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((3-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)propyl)thio)-6-oxo-4-(pyridin-4-yl)-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4\u0026nbsp;l)\u003c/span\u003e: Brown solid, m.p.\u0026nbsp;147.8-149.8\u0026nbsp;\u0026deg;C; yield: 50.2%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 8.75 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.8\u0026nbsp;Hz, 2H, Piperidinyl-H), 7.85 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;4.5, 1.5\u0026nbsp;Hz, 2H, Piperidinyl-H), 7.34 (s, 2H, Ph-H), 6.84 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.1\u0026nbsp;Hz, 1H, Ph-H), 6.50 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.1\u0026nbsp;Hz, 1H, Ph-H), 4.03 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.0\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.91 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.86 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.82 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.73 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.36 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 2.15\u0026ndash;2.07 (m, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.58, 167.58, 165.46, 164.28, 160.77, 158.65, 153.18, 152.20, 150.65, 142.98, 140.14, 139.92, 125.93, 122.83, 115.85, 108.89, 106.13, 96.42, 94.67, 93.62, 70.46, 60.65, 56.58, 56.52, 30.01, 27.84; HRMS calcd for C\u003csub\u003e33\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eN\u003csub\u003e4\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 659.1806, found 659.1811.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4\u0026nbsp;m)\u003c/span\u003e: Yellow solidd, m.p.\u0026nbsp;227.0-228.5\u0026nbsp;\u0026deg;C; yield: 42.9%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.93\u0026ndash;7.87 (m, 2H, Ph-H), 7.56\u0026ndash;7.46 (m, 3H Ph-H), 7.33 (m, 2H, Ph-H), 6.83 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.1\u0026nbsp;Hz, 1H, Ph-H), 6.49 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.0\u0026nbsp;Hz, 1H, Ph-H), 3.95 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.8\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.83 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.0\u0026nbsp;Hz, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.74 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.27 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.7\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 1.81 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;14.0, 6.5\u0026nbsp;Hz, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.63, 166.53, 164.23, 160.74, 158.62, 153.13, 152.05, 140.27, 139.86, 132.10, 129.03, 128.95, 125.99, 116.44, 108.90, 106.13, 96.38, 93.56, 71.38, 60.65 1, 56.56, 56.51, 30.44, 29.00, 26.05; HRMS calcd for C\u003csub\u003e35\u003c/sub\u003eH\u003csub\u003e33\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 672.2010, found 672.2007.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-4-(m-tolyl)-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4n)\u003c/span\u003e: Yellow solidd, m.p.\u0026nbsp;207.6-209.5\u0026nbsp;\u0026deg;C; yield: 45.8%;\u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.69 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.8\u0026nbsp;Hz, 2H, Ph-H), 7.41\u0026ndash;7.35 (m, 2H, Ph-H), 7.34 (s, 2H, Ph-H), 6.82 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.49 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.3\u0026nbsp;Hz, 1H, Ph-H), 3.96 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.7\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.83 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.26 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.8\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.32 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 1.88\u0026ndash;1.72 (m, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.60, 164.22, 160.74, 158.61, 153.12, 152.03, 140.26, 139.87, 138.30, 132.71, 129.47, 128.84, 126.26, 125.98, 116.41, 108.90, 106.14, 96.36, 93.55, 71.36, 60.64, 56.50, 30.42, 29.01, 26.14, 21.33; HRMS calcd for C\u003csub\u003e36\u003c/sub\u003eH\u003csub\u003e35\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 686.2167, found 686.2161.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-4-(p-tolyl)-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4o)\u003c/span\u003e: White solid, m.p.\u0026nbsp;229.8-231.2\u0026nbsp;\u0026deg;C; yield: 59.1%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.82 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.2\u0026nbsp;Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 7.27 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.1\u0026nbsp;Hz, 2H, Ph-H), 6.83 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.49 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 3.97 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.8\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 9H,3\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.27 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.7\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 2.32 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 1.81 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11.6, 6.6\u0026nbsp;Hz, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.62, 167.36, 166.21, 164.23, 160.75, 158.6, 153.12, 151.97, 142.47, 140.26, 139.87, 132.85, 129.51, 129.10, 125.98, 116.57, 108.89, 106.11, 96.37, 93.56, 92.76, 71.33, 60.64, 56.54, 56.51, 30.38, 28.96, 26.12, 21.45; HRMS calcd for C\u003csub\u003e36\u003c/sub\u003eH\u003csub\u003e35\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 686.2167, found 686.2191.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4p)\u003c/span\u003e: Yellow solidd, m.p.\u0026nbsp;236.4-237.8\u0026nbsp;\u0026deg;C; yield: 51.9%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.97 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.9\u0026nbsp;Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 7.04 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9.0\u0026nbsp;Hz, 2H, Ph-H), 6.82 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.48 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 3.97 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.6\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 9H, 3\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.80 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.74 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.28 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.6\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 1.88\u0026ndash;1.76 (m, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.64, 164.2, 162.63, 160.74, 158.59, 153.12, 151.95, 140.28, 139.88, 131.16, 125.98, 116.90, 114.39, 108.87, 106.11, 96.36, 93.55, 71.35, 60.64, 56.51, 55.87, 30.38, 28.99, 26.12; HRMS calcd for C\u003csub\u003e36\u003c/sub\u003eH\u003csub\u003e35\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e10\u003c/sub\u003eS [M]\u003csup\u003e+\u003c/sup\u003e: 701.2038, found 701.2026.\u003c/p\u003e \u003cp\u003e \u003cem\u003e4-(3-chlorophenyl)-2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4q)\u003c/span\u003e: Yellow solidd, m.p.\u0026nbsp;137.2-139.2\u0026nbsp;\u0026deg;C; yield: 41.8%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.81 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.2, 1.3\u0026nbsp;Hz, 2H Ph-H), 7.59\u0026ndash;7.48 (m, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 6.82 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.49 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 3.95 (s, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 9H, 3\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.74 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.16 (s, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 1.79 (s, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.63, 165.88, 164.21, 160.75, 158.61, 153.12, 152.03, 140.30, 139.86, 133.53, 131.09, 130.76, 128.51, 127.53, 126.01, 108.91, 106.14, 96.36, 93.55, 71.47, 60.64, 56.52, 56.50, 30.24, 29.10, 26.25; HRMS calcd for C\u003csub\u003e35\u003c/sub\u003eH\u003csub\u003e32\u003c/sub\u003eClN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 706.1621, found706.1605.\u003c/p\u003e \u003cp\u003e \u003cem\u003e4-(4-chlorophenyl)-2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4r)\u003c/span\u003e: Yellow solidd, m.p.\u0026nbsp;129.5-131.8\u0026nbsp;\u0026deg;C; yield: 61.5%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.84 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.6\u0026nbsp;Hz, 2H, Ph-H), 7.70 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.6\u0026nbsp;Hz, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 6.83 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.49 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 3.96 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.8\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.91 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.85 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.74 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.27 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.8\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 1.81 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;14.8, 6.6\u0026nbsp;Hz, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.65, 166.79, 166.44, 164.24, 160.75, 158.60, 153.13, 151.96, 140.28, 139.90, 134.84, 132.05, 131.06, 125.97, 116.27, 108.88, 106.13, 96.41, 93.59, 71.36, 60.65, 56.57, 56.53, 30.42, 28.93, 26.08; HRMS calcd for C\u003csub\u003e35\u003c/sub\u003eH\u003csub\u003e32\u003c/sub\u003eClN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 706.1621, found 706.1592.\u003c/p\u003e \u003cp\u003e \u003cem\u003e4-(3-bromophenyl)-2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4\u0026nbsp;s)\u003c/span\u003e: Yellow solidd, m.p.\u0026nbsp;119.5-121.4\u0026nbsp;\u0026deg;C; yield: 30.5%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.99 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.7\u0026nbsp;Hz, 1H, Ph-H), 7.90 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.8\u0026nbsp;Hz, 1H, Ph-H), 7.73 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.9\u0026nbsp;Hz, 1H, Ph-H), 7.46 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.9\u0026nbsp;Hz, 1H, Ph-H), 7.35 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9.9\u0026nbsp;Hz, 2H, Ph-H), 6.82 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.1\u0026nbsp;Hz, 1H, Ph-H, Ph-H), 6.49 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.9\u0026nbsp;Hz, 1H, Ph-H), 3.96 (s, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.1\u0026nbsp;Hz, 12H, 4\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.73 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.8\u0026nbsp;Hz, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.26 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.5\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 1.80 (s, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.62, 165.89, 164.21, 160.73, 158.60, 153.11, 152.03, 140.26, 139.83, 137.89, 134.64, 131.56, 131.12, 128.06, 125.98, 122.05, 116.14, 108.89, 106.11, 96.36, 93.54, 71.37, 60.64, 56.50, 30.44, 28.97, 26.10; HRMS calcd for C\u003csub\u003e35\u003c/sub\u003eH\u003csub\u003e32\u003c/sub\u003eBrN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 750.1115, found 750.1126.\u003c/p\u003e \u003cp\u003e \u003cem\u003e4-(4-bromophenyl)-2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4t)\u003c/span\u003e: White solid, m.p.\u0026nbsp;153.6-155.4\u0026nbsp;\u0026deg;C; yield: 46.1%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.86\u0026ndash;7.81 (m, 2H, Ph-H), 7.73\u0026ndash;7.66 (m, 2H, Ph-H), 7.35 (s, 2H, Ph-H), 6.83 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.49 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 3.96 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.8\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.91 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.85 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.74 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.27 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.8\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 1.81 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;14.8, 6.6\u0026nbsp;Hz, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.65, 166.79, 166.44, 164.24, 160.75, 158.60, 153.13, 151.96, 140.28, 139.90, 134.84, 132.05, 131.06, 125.97, 116.27, 108.88, 106.13, 96.41, 93.59, 71.36, 60.65, 56.57, 56.53, 30.42, 28.93, 26.08; HRMS calcd for C\u003csub\u003e35\u003c/sub\u003eH\u003csub\u003e32\u003c/sub\u003eBrN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 750.1115, found 750.1108.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-4-(3-fluorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4u)\u003c/span\u003e: White solid, m.p.\u0026nbsp;119.8-121.64\u0026nbsp;\u0026deg;C; yield: 70.8%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.73 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.9\u0026nbsp;Hz, 1H, Ph-H), 7.65 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9.8, 2.0\u0026nbsp;Hz, 1H, Ph-H), 7.55 (td, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 6.1\u0026nbsp;Hz, 1H, Ph-H), 7.41\u0026ndash;7.36 (m, 1H, Ph-H), 7.35 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.9\u0026nbsp;Hz, 2H, Ph-H), 6.83 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.48 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 3.95 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.5\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 9H, 3\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.73 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.24 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.4\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 1.80 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.2\u0026nbsp;Hz, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.63, 164.21, 160.94, 160.73, 158.60, 153.12, 152.02, 140.27, 139.84, 131.09, 125.99, 125.22, 115.87, 115.64, 108.88, 106.10, 96.35, 93.53, 71.38, 60.64, 56.51, 30.41, 28.98, 26.04; \u003csup\u003e19\u003c/sup\u003eF NMR (376\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ -112.28; HRMS calcd for C\u003csub\u003e35\u003c/sub\u003eH\u003csub\u003e32\u003c/sub\u003eFN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 690.1916, found 690.1915.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-4-(4-fluorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4v)\u003c/span\u003e: White solid, m.p.\u0026nbsp;223.0-224.8\u0026nbsp;\u0026deg;C; yield: 25.3%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 7.99 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.9, 5.5\u0026nbsp;Hz, 2H, Ph-H), 7.38\u0026ndash;7.32 (m, 4H, Ph-H), 6.84 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.50 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 3.96 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.8\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.0\u0026nbsp;Hz, 9H, 3\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.74 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.27 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.7\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 1.81 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9.6, 4.5\u0026nbsp;Hz, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.67, 164.24, 160.72, 158.61, 153.12, 152.00, 140.27, 139.82, 131.81, 125.98, 116.54, 116.21, 115.99, 108.86, 106.07, 96.40, 93.56, 71.39, 60.64, 56.51, 30.39, 28.97, 26.07; \u003csup\u003e19\u003c/sup\u003eF NMR (376\u0026nbsp;MHz, DMSO) δ -105.82; HRMS calcd for C\u003csub\u003e35\u003c/sub\u003eH\u003csub\u003e32\u003c/sub\u003eFN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 690.1916, found 690.1894 .\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-4-(furan-2-yl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4w)\u003c/span\u003e: Black solid, m.p.\u0026nbsp;236.8-238.7\u0026nbsp;\u0026deg;C; yield: 73.2%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 8.10 (s, 1H, Ph-H), 7.45 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.4\u0026nbsp;Hz, 1H, Ph-H), 7.36 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;4.2\u0026nbsp;Hz, 2H, Ph-H), 6.82 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.71 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.5, 1.7\u0026nbsp;Hz, 1H, Ph-H), 6.49 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.1\u0026nbsp;Hz, 1H, Ph-H), 4.00 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.2\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.85 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.76\u0026ndash;3.72 (m, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.29 (s, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 1.81 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.9\u0026nbsp;Hz, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.67, 164.22, 160.71, 158.59, 154.86, 153.11, 151.97, 149.77, 148.57, 140.29, 139.80, 125.99, 118.73, 115.71, 113.67, 108.85, 106.03, 96.38, 93.53, 71.34, 60.65, 56.50, 30.29, 28.91, 26.04; HRMS calcd for C\u003csub\u003e33\u003c/sub\u003eH\u003csub\u003e31\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e10\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 662.1803, found 662.1790.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((4-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)butyl)thio)-6-oxo-4-(pyridin-4-yl)-1,6-dihydropyrimidine-5-carbonitrile\u003c/em\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003e(4x)\u003c/span\u003e: Yellow solidd, m.p.\u0026nbsp;213.8-215.8\u0026nbsp;\u0026deg;C; yield:56.6%; \u003csup\u003e1\u003c/sup\u003eH NMR (400\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 8.75 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.8\u0026nbsp;Hz, 2H, Ph-H), 7.81 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;4.5, 1.6\u0026nbsp;Hz, 2H, Ph-H), 7.34 (s, 2H, Ph-H), 6.83 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 6.49 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.2\u0026nbsp;Hz, 1H, Ph-H), 3.95 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.8\u0026nbsp;Hz, 2H, -O-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-), 3.90 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.84 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.83 (s, 6H, 2\u0026thinsp;\u0026times;\u0026thinsp;Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.73 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e), 3.28 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.7\u0026nbsp;Hz, 2H, -O-CH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e-S-), 1.85\u0026ndash;1.75 (m, 4H, -O-CH\u003csub\u003e2\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e2\u003c/span\u003e\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e-S-); \u003csup\u003e13\u003c/sup\u003eC NMR (101\u0026nbsp;MHz, DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e6\u003c/sub\u003e) δ 172.64, 167.52, 165.49, 164.23, 161.16, 160.72, 158.60, 153.12, 152.01, 150.62, 142.98, 140.27, 139.82, 125.97, 122.79, 115.76, 108.86, 106.07, 96.38, 94.82, 93.56, 71.35, 60.65, 56.55, 56.50, 30.52, 28.97, 25.97, 21.24; HRMS calcd for C\u003csub\u003e34\u003c/sub\u003eH\u003csub\u003e32\u003c/sub\u003eN\u003csub\u003e4\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003eS [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e: 673.1963, found 673.1943.\u003c/p\u003e "},{"header":"Conclusions","content":" \u003cp\u003eIn summary, aiming to develop novel and high-efficient agents with better biological activities, a series of pyrimidine-containing 4\u003cem\u003eH\u003c/em\u003e-chromen-4-one derivatives were designed and synthesized. Antibacterial bioassys showed that most of compounds exhibited significant antibacterial activity against \u003cem\u003eXac\u003c/em\u003e,\u003cem\u003eXoo\u003c/em\u003e and \u003cem\u003eRs\u003c/em\u003e. Among them, the EC\u003csub\u003e50\u003c/sub\u003e values of compound \u003cb\u003e4c\u003c/b\u003e agains \u003cem\u003eXac\u003c/em\u003e and \u003cem\u003eXoo\u003c/em\u003e were 15.5 and 14.9\u0026nbsp;\u0026micro;g/mL respectively, which were better than BT (51.7, 70.1%, respectively) and TC (77.9, 95.8%, respectively), compounds \u003cb\u003e4\u0026nbsp;h\u003c/b\u003e displayed appreciable activity against \u003cem\u003eRs\u003c/em\u003e, with the EC\u003csub\u003e50\u003c/sub\u003e values of 14.7\u0026nbsp;\u0026micro;g/mL, the result superior to BT (and 52. 8\u0026nbsp;\u0026micro;g/mL) and TC (72.1\u0026nbsp;\u0026micro;g/mL). Compound \u003cb\u003e4c\u003c/b\u003e demonstrated excellent curative activity and protection activity against bacterial blight of rice with the percentage inhibition of 42.4 and 49.2%, respectively, which were better than BT (35.2, 39.1%, respectively) and TC (30.8, 27.3%, respectively). Furthermore, the mechanism of compound \u003cb\u003e4c\u003c/b\u003e against \u003cem\u003eXoo\u003c/em\u003e was confirmed by scanning electron microscope, the results showed that the compound destroyed the cell membrane structure of the bacteria, and the damage of the cell membrane was more serious as the concentration increased. These results indicated that the pyrimidine-containing 4\u003cem\u003eH\u003c/em\u003e-chromen-4-one derivatives possess better antibacterial activities and could be further studied as potential replacement templates in the search for novel antibacterial agents.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis section are not applicable for this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis section are not applicable for this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and material\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe have presented all our main data in the form of tables and figures. Meanwhile, all the copies of \u003csup\u003e1\u003c/sup\u003eH NMR, \u003csup\u003e13\u003c/sup\u003eC NMR, \u003csup\u003e19\u003c/sup\u003eF NMR and HRMS for the title compounds were presented in the Support Information. The datasets supporting the conclusions of the article are included within the article and the Support Information.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe gratefully acknowledge the National Key Research and Development Program of China (No.2018YFD02011026), the National Nature Science Foundation of China (No. 21867003), the Science Fund of Guizhou Province (Nos. 20191105, 20192452, 20162533).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026rsquo; contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study is an outcome of constructive discussion with W Xue. SJ Su, M Chen carry out their synthesis and characterization experiments and carried out the \u003csup\u003e1\u003c/sup\u003eH NMR, \u003csup\u003e13\u003c/sup\u003eC NMR, \u003csup\u003e19\u003c/sup\u003eF NMR and HRMS spectral analyses, XM Tang and F Peng performed the antibacterial activity; TT Liu, Q Zhou, H Luo and M He assists in scanning electron microscope; SJ Su, M Chen were involved in the drafting of the manuscript and revising the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgement\u003c/em\u003e\u003cem\u003es\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthor details\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZou LF, Li YR, Chen, GY (2011) A non-marker mutagenesis strategy to generate poly-hrp gene mutants in the rice pathogen \u003cem\u003eXanthomonas oryzae pv. oryzicola\u003c/em\u003e.\u0026nbsp;\u0026nbsp;Agric Sci China 10 : 1139-1150\u003c/li\u003e\n\u003cli\u003eLi P, Tian PY, Chen YZ, Song XP, Xue W, Jin, LH, Hu DY, Yang S, Song BA (2017) Novel bisthioether derivatives containing a 1,3,4-oxadiazole moiety: design, synthesis, antibacterial and nematocidal activities. 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Pharmacol Res 122 : 66 \u0026ndash;77\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"4H-Chromen-4-one derivatives, pyrimidine, antibacterial activity, scanning electron microscopy","lastPublishedDoi":"10.21203/rs.3.rs-92183/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-92183/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA series of pyrimidine-containing 4\u003cem\u003eH\u003c/em\u003e-chromen-4-one derivatives were designed and synthesized by combining bioactive substructures. All compounds were characterized using \u003csup\u003e1\u003c/sup\u003eH NMR, \u003csup\u003e13\u003c/sup\u003eC NMR, \u003csup\u003e19\u003c/sup\u003eF NMR and HRMS. Preliminary biological activity results showed that most of title compounds displayed significant inhibitory activity against \u003cem\u003eXanthomonas axonopodis pv. Citri\u003c/em\u003e (\u003cem\u003eXac\u003c/em\u003e), \u003cem\u003eXanthomonas oryzae pv. oryzae\u003c/em\u003e (\u003cem\u003eXoo\u003c/em\u003e) and \u003cem\u003eRalstonia solanacearum\u003c/em\u003e (\u003cem\u003eRs\u003c/em\u003e). In particular, compound \u003cstrong\u003e4c\u003c/strong\u003e demonstrated a good inhibitory effect against \u003cem\u003eXac\u003c/em\u003e and \u003cem\u003eXoo\u003c/em\u003e, with half-maximal effective concentration(EC\u003csub\u003e50\u003c/sub\u003e) values of 15.5 and 14.9 μg/mL respectively, and that of compound \u003cstrong\u003e4h \u003c/strong\u003eshowed the best antibacterial activity against \u003cem\u003eRs\u003c/em\u003e with an EC\u003csub\u003e50\u003c/sub\u003e value of 14.7 μg/mL, These results \u0026nbsp;were better than both bismerthiazol (BT, 51.7, 70.1 and 52.7 μg/mL, respectively) and thiodiazole copper (TC, 77.9, 95.8 and 72.1 μg/mL respectively). \u003cem\u003eIn vivo\u003c/em\u003e antibacterial activity results indicated that compound \u003cstrong\u003e4c\u003c/strong\u003e \u0026nbsp;displayed better curative(42.4%) and protective (49.2%) activities for reducing rice bacterial leaf blight than both BT (35.2, 39.1%) and TC (30.8, 27.3%). The mechanism of compound \u003cstrong\u003e4c\u003c/strong\u003e against \u003cem\u003eXoo\u003c/em\u003e was analysed through scanning electron microscopy (SEM). \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eResults showed that\u003cstrong\u003e \u003c/strong\u003ethe compound destroied the bacterial cell membrane structure. These results indicated that pyrimidine-containing 4\u003cem\u003eH\u003c/em\u003e-chromen-4-one derivatives are valuable in the research of new agrochemicals.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Design, Synthesis and Antibacterial Activity of Novel Pyrimidine-Containing 4H-Chromen-4-one Derivatives","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-10-19 14:40:24","doi":"10.21203/rs.3.rs-92183/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8a1f6c14-865a-4826-85bd-4a9928d3abdc","owner":[],"postedDate":"October 19th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":820756,"name":"Organic Chemistry"}],"tags":[],"updatedAt":"2020-10-19T14:40:24+00:00","versionOfRecord":[],"versionCreatedAt":"2020-10-19 14:40:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-92183","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-92183","identity":"rs-92183","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}