Novel flavonoid derivatives containing benzothiazole as potential antiviral agents: design, synthesis, and biological evaluation

Novel flavonoid derivatives containing benzothiazole as potential antiviral agents: design, synthesis, and biological evaluation | 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 Novel flavonoid derivatives containing benzothiazole as potential antiviral agents: design, synthesis, and biological evaluation Jiao Tian, Chunmei Hu, Yuhong Wang, Qing Zhou, Xingping Luo, Jieyu Li, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5025191/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 flavonol derivatives containing benzothiazole were designed and synthesized. The structures of all the compounds were characterized by NMR and HRMS. The results of the bioactivity assay showed that some of the target compounds possessed outstanding in vivo antiviral activity against the tobacco mosaic virus (TMV). Among them, the median effective concentration (EC 50 ) of L20 was 90.5 µg/mL for curative activities against TMV, which was better than that of ningnanmycin (NNM: 252.0 µg/mL). The microcalorimetric thermophoresis (MST) and molecular docking experiments showed that L20 had a strong binding ability with TMV-CP; the malondialdehyde (MDA) and superoxide dismutase assay (SOD) activity measurements also fully confirmed that L20 stimulated the plant immune system and strengthened the plant's resistance to diseases by lowering the MDA content and increasing the SOD activity. In addition, the chlorophyll content test experiment found that L20 could reduce the destructive effect of viruses on chloroplasts, increase the content of chlorophyll, and promote photosynthesis. In conclusion, above experimental results suggested that flavonol derivatives containing benzothiazole could be further investigated as new plant virus antiviral drugs. flavonoid benzothiazole antiviral activity mechanism of action Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Highlights In this paper, 26 flavonoid derivatives containing benzothiazole were designed and synthesized. L20 exhibited excellent antiviral activity, the EC 50 value of curative activities was 90.5 μ g/mL, which was better than that of ningnanmycin (NNM: 252.0 μg/mL) Further mechanistic studies have shown that L20 not only has a strong binding ability with TMV-CP, but also could effectively stimulate the plant`s immune system and reduce the destructive effect of viruses on chloroplasts. 1. Introduction Plant virus diseases present a significant menace to global crop yields and quality annually. Plant viruses exhibit obligate parasitism within host cells; once infected with viruses, plants often remain so for their entire lifespan hence earning the moniker “plant cancer”[ 1 , 2 ]. Notably among them is tobacco mosaic virus (TMV), one of the most prevalent and severe global viral pathogens that spreads via sap transmission with enduring extracellular stability. Its infections significantly compromise crop quality across various cultivars such as tobacco, tomatoes, cucumbers, and peppers along with ornamental plants[ 3 , 4 , 5 ], posing substantial threats to agricultural productivity and resulting in annual global losses exceeding 100 million US dollars due to TMV[ 6 ]. While conventional antiviral medications may offer some control over TMV infections, prolonged usage has led to diminished efficacy. Hence, the imperative need for developing novel, efficient, and eco-friendly antiviral agents. Flavonoid is widely found in various plants and account for about one-third of the total flavonoid compounds. They have numerous vital pharmacological effects and biological activities, such as antioxidant[ 7 ], antibacterial[ 8 , 9 ], antitumor[ 10 , 11 ], antiviral[ 12 , 13 , 14 ], etc. As a natural active substance with multiple good physiological activities, widespread sources, and high safety, flavonoid is increasingly favored by researchers. Benzothiazole, also known as 1,3-thiazin-2-ylidenes, is a bicyclic heterocyclic compound with a thiazole ring. Many pesticide companies have developed thiazole-based fungicides, such as benzothiostrobin and benthiavalicarb-isopropyl. Due to its excellent structural characteristics, reactivity, and coordination properties, it has a variety of biological activities, such as antibacterial[ 15 , 16 , 17 ], antiviral[ 18 , 19 ], and insect-killing activities[ 20 ]. In addition, one of the fundamental goals of medicinal organic chemistry is to design, synthesize, and manufacture molecules that are beneficial to humans. Compounds containing thiazoles have broad potential for pharmaceutical applications, such as anti-cancer[ 21 , 22 ], anti-inflammatory[ 23 ], etc. Amides are a strong active ingredient in pesticides, and studies have shown that amides have broad-spectrum antibacterial[ 24 , 25 ], antiviral[ 26 ], herbicidal[ 27 ], and insecticidal activities[ 28 ]. On this basis, a series of flavonoid derivatives containing benzothiazole were synthesized. Through biological activity screening and mechanism studies, the screened L20 has significantly better antiviral activity than commercially available agent NNM (Fig. 1 ). Figure 1 2 Results and discussion 2.1 Chemistry The route by which the target compounds were synthesized was shown in Scheme 1 . The intermediate 1 was synthesized from different o -hydroxyacetophenone and various substituted benzaldehydes. Intermediate 2 was synthesized by intermediate 1 via Algar-Flynn-Oyamada reaction. Intermediate 3 was prepared by substitution reaction of 2-aminobenzothiazole and chloroacetyl chloride. Finally, intermediate 2 and intermediate 3 underwent a sub-stitution reaction to obtain L1-L26 . The structures of the compounds were characterized by NMR and HRMS spectrums and the data were offered in the Supporting Information. Scheme 1 2.2 Spectral characteristic of title compounds 2.3 Antiviral activity of L1-L26 against TMV in vivo The resistance of L1-L26 to TMV at a concentration of 500 µg/mL was tested by the half-leaf spot method using NNM as positive control. As shown in Table 1 , the curative activities of L17 , L20 , and L24 against TMV was 67.5, 71.8, and 66.4%, respectively, which was superior to that of NNM (60.1%); and the protective activities of L20 and L21 were 64.9 and 63.9%, respectively, which were both superior to that of NNM (61.2%). The tobacco leaf morphology of L20 and NNM against TMV in vivo were shown in Fig. 2 . The EC 50 values of the compounds against TMV were further assayed and were shown in Table 2 . The EC 50 values of curative activities of L17 , L20 , and L24 were 223.2, 90.5, and 146.9 µg/mL, respectively, which were superior to that of NNM (252.0 µg/mL); and the EC 50 values of protective activities of L20 and L21 were 202.2 and 162.6 µg/mL were better than that of the NNM (204.2 µg/mL). Table 1 Antiviral activity of L1-L26 against TMV at 500 µ g/mL in vivo . a Compounds R 1 R 2 Curative (%) Protective (%) Inactivating (%) L1 H 5-Br 47.6 ± 1.1 35.9 ± 2.7 40.5 ± 4.1 L2 4-CH 3 5-Br 57.7 ± 5.3 53.5 ± 5.3 44.3 ± 3.7 L3 3-OCH 3 5-Br 54.3 ± 2.0 35.3 ± 7.4 31.0 ± 2.3 L4 4-F 5-Br 50.6 ± 1.9 49.4 ± 2.7 45.3 ± 4.8 L5 4-t-Bu 5-Br 53.0 ± 2.0 52.7 ± 8.3 47.0 ± 3.5 L6 H 6-Cl 46.2 ± 1.8 53.8 ± 9.1 31.1 ± 2.4 L7 4-CH 3 6-Cl 50.4 ± 2.6 34.0 ± 4.5 53.0 ± 2.8 L8 3-OCH 3 6-Cl 43.3 ± 5.2 58.7 ± 1.6 46.5 ± 2.1 L9 4-F 6-Cl 41.2 ± 4.2 25.1 ± 1.6 29.6 ± 4.1 L10 4-t-Bu 6-Cl 37.3 ± 3.4 47.4 ± 3.7 47.6 ± 4.6 L11 2-OCH 3 6-Cl 32.6 ± 3.4 49.6 ± 5.4 34.1 ± 2.2 L12 H H 54.5 ± 3.5 43.2 ± 2.6 49.5 ± 3.2 L13 4-CH 3 H 53.0 ± 3.4 60.3 ± 3.7 52.6 ± 1.8 L14 3-OCH 3 H 25.5 ± 4.4 59.5 ± 5.1 34.9 ± 1.9 L15 4-F H 50.1 ± 4.1 50.0 ± 4.2 42.5 ± 3.6 L16 4-t-Bu H 55.2 ± 3.5 56.7 ± 4.5 45.0 ± 4.2 L17 4-Cl H 67.5 ± 2.1 50.1 ± 1.7 45.5 ± 3.3 L18 H 4-CH 3 53.6 ± 1.7 52.0 ± 7.9 38.4 ± 4.3 L19 4-CH 3 4-CH 3 50.8 ± 3.3 57.6 ± 5.2 63.7 ± 1.4 L20 3-OCH 3 4-CH 3 71.8 ± 1.6 64.9 ± 1.9 55.9 ± 1.3 L21 4-F 4-CH 3 49.8 ± 0.2 63.9 ± 2.1 52.8 ± 1.1 L22 4-t-Bu 4-CH 3 52.6 ± 5.0 59.7 ± 1.6 51.3 ± 1.3 L23 4-Cl 4-CH 3 36.8 ± 4.5 30.1 ± 4.3 44.0 ± 2.1 L24 H 6-OCH 3 66.4 ± 3.5 42.2 ± 3.7 46.0 ± 4.7 L25 4-CH 3 6-OCH 3 53.3 ± 5.3 51.2 ± 5.6 34.0 ± 1.8 L26 3-OCH 3 6-OCH 3 39.2 ± 3.4 24.3 ± 4.1 23.3 ± 3.6 NNM b - - 60.1 ± 4.4 61.2 ± 1.9 90.7 ± 2.6 a Vales are mean ± SD of three replicates. b The commercial antiviral agent Ningnanmycin (NNM). Table 2 EC 50 values of some of the target compounds against TMV in vivo . a Compounds Regression equation r EC 50 (mg/mL) Curative activity L17 y = 1.2211x + 2.1321 0.9807 223.16 L20 y = 0.7249x + 3.5816 0.9693 90.52 L24 y = 0.7120x + 3.4571 0.9814 146.88 NNM b y = 0.7770x + 3.1341 0.9659 252.03 Protective activity L20 y = 0.6666x + 3.4630 0.9866 202.18 L21 y = 0.6521x + 3.5581 0.9794 162.55 NNM y = 0.7357x + 3.3005 0.9616 204.19 a Average of three replicates. b The commercial antiviral agent. Ningnanmycin (NNM) Table 1 Figure 2 Table 2 2.4 Structure-activity relationship analysis The structure-activity relationship of the synthesized flavonol derivatives containing benzothiazole was evaluated. Combining the activity data in Table 1 and Table 2 , it is evident that the substituent group has a greater influence on the anti-TMV activity of the compounds. The compounds had better anti-TMV activity when R 1 = H and R 2 was an electron-donating substituent. For example, curative activity: L24 > L6 (R 2 = OCH 3 : 66.4% > R 2 = Cl: 46.2%), L18 > L1 (R 2 = CH 3 : 53.6% > R 2 = Br: 47.6%). In addition, the compounds have better anti-TMV activity when R 2 is the same substituent and R 1 is an electron-donating substituent, such as when R 2 = Br, the curative activity was L2 > L4 (R 1 = CH 3 : 57.7% > R 1 = F: 50.6%); when R 2 = Cl, L7 > L9 (R 1 = CH 3 : 50.4% > R 1 = F: 41.2%); when R 2 = CH 3 , L20 > L21 (R 1 = CH 3 : 71.8% > R 1 = F: 49.8%). From the above analysis, it can be seen that when both R 1 and R 2 are electron-donating groups, it can significantly increase the anti-TMV activity of the compounds. For example, the EC 50 value of the antiviral curative activity of L20 (R 1 = 3-OCH 3 , R 2 = 4-CH 3 ) was 90.5 µg/mL, which was significantly lower than that of the other compounds and NNM. 2.5 Binding ability of L20, L23, and NNM to TMV-CP TMV-CP is a key functional protein of TMV that self-assembles with viral RNA to form virus. The interactions of L20 , L23 , and NNM with TMV-CP were further analyzed by MST. The smaller the value of the dissociation constant K d , the stronger the binding ability of the compounds to TMV-CP. As shown in Fig. 3 , the K d values of L20 , L23 , and NNM treated with TMV-CP were 0.027 ± 0.012, 0.153 ± 0.036, and 0.061 ± 0.030 µM, respectively. The results showed that the binding ability of L20 to TMV-CP was better than that of L23 and NNM, which further indicated that L20 had better antiviral activity, which agreed with the results of the preliminary screening for anti-TMV activity. Figure 3 2.6 Molecular docking of L20 and NNM with TMV-CP The molecular docking results were shown in Fig. 4 , where the bioactive molecules L20 and NNM were embedded in the same active protein pocket of TMV and completed self-assembly with the TMV-CP subunits to form non-covalent bonding interactions. L20 interacted with amino acid residues (ASN-73, ARG-134, LYS-253, LYS-268, ASP-266, PRO-263) of TMV-CP through traditional hydrogen-bonding, carbon-hydrogen-bonding, pi-cation, alkyl, and pi-alkyl. Among them, amino acid residue LYS-268 formed two pi-cation bonds (2.51 Å, 3.08 Å) and one hydrogen bond (2.19 Å) with the aryl ring, thiazole ring, and amino group of L20 benzothiazole, respectively. In contrast, NNM has only one hydrogen bond with the amino acid residue LYS-268 (1.92 Å). In addition, the oxygen atom on the carbonyl group in L20 forms a carbon-hydrogen bond with amino acid residue PRO-263 (2.25 Å), and NNM forms a carbon-hydrogen bond with amino acid residue GLU-131 (4.30 Å), however, the carbon-hydrogen bond formed due to L20 is shorter than that of NNM. After visualization by Pymol, it is more intuitive to realize that L20 binds to TMV-CP more tightly and with more force than NNM. Figure 4 2.7 MDA content analysis When the antioxidant mechanism in the body fails to maintain the generation and scavenging of reactive oxygen radicals in a balanced state during plant organ senescence or under adverse conditions, it leads to the peroxidation of membrane lipids of the tissues or organs, which in turn leads to the production of MDA. Therefore, the degree of membrane lipid peroxidation can be detected through MDA to indirectly valuate the degree of damage to the membrane system and plant stress tolerance. As shown in Fig. 5 , the content of MDA in the leaves of the CK group showed an increasing trend with time, and reached its peak on the 5th day, indicating that the plants contained antioxidant enzymes in the plant body, which had a certain regulating effect during the aging process. The content of MDA in the L20 group plants was lower than that in the CK group, which indicated that L20 was able to inhibit the adversity stress in tobacco. The content of MDA in the TMV group was significantly elevated and was the highest among the treatment groups; especially on the 7th day, it was more than twice as long as the corresponding time in the CK group, which fully reflected the serious damage of TMV to tobacco. The L20 + TMV group was significantly lower than that of the TMV group, which indicated that L20 could inhibit the injury of TMV to the leaves and slow down the speed of its destruction. In summary, the L20 can inhibit TMV infected plants and enhance the antioxidant capacity and disease resistance of plants. Figure 5 2.8 Effects of L20 on SOD activity Superoxide Dismutase (SOD) plays a vital role in the biological antioxidant system, which can counteract and block the damage caused by oxygen radicals to the cells, and it also can repair the damaged cells in time to restore the damage caused by oxygen radicals to the cells. The increase in SOD activity can enhance the antiviral ability of plants. As shown in Fig. 6 , with the growth of time, the overall SOD activity in tobacco showed a trend of increasing and then slow decreasing. The SOD activity in the TMV group was significantly higher than that in the CK group, which was due to the fact that the plant activated the SOD system for self-protection immediately after being infected by the virus; the L20 group and the L20 + TMV group reached the peak value 3rd, and after that, the SOD activity showed a slow decreasing trend, but the overall activity was higher than that of the CK group and TMV group, it can be known that L20 can increase SOD activity in plants, enhance the ability to scavenge superoxide radicals, and improve the disease resistance of plants. Figure 6 2.9 Analysis of chlorophyll content Chlorophyll content is closely related to photosynthesis. The virus infests tobacco and proliferates in the host body, which will destroy the chloroplasts of the plant and interfere with the synthesis of chlorophyll, thus causing the yellowing of the leaves. As can be seen from Fig. 7 , the chlorophyll content of the CK group and TMV group showed a general trend of increasing and then decreasing, reaching a peak on the 5th day, and then gradually decreasing with time as the plants senesces. On the 5th day, it was obvious that the chlorophyll content of the CK-group was higher than that of the TMV group, which was due to the fact that the chloroplasts were damaged after the TMV infection. After the 3rd day, it can be seen that the difference in chlorophyll content between the groups became more and more obvious, in which the L20 group was higher than the CK-group, and the L20 + TMV group was higher than the TMV group, which revealed that the L20 could alleviate the destructive effect of the virus on the chloroplasts, increase the content of chlorophyll indexes, and promote photosynthesis, thus increasing the resistance of tobacco to the disease Figure 7 3 Discussion In this study, 26 flavonol derivatives containing benzothiazole were synthesized. The antiviral activity experiments indicated that L20 possessed better inhibitory effects in terms of curative and protective activities, with EC 50 values of 90.5 µg/mL, which were better than those of NNM (252.0 µg/mL). It is noteworthy that the MST experiments used the TMV-CP protein as a target for the antiviral compounds, which indicated that L20 showed a strong affinity. Molecular docking simulation consequences revealed that L20 had excellent binding ability, and the results were consistent with the MST. Further experimental results showed that L20 could participate in the regulation of membrane lipid per-oxidation, preventing TMV infection in plants and thereby enhancing their antioxidant and defense abilities, and that L20 may increase the ability of the host to scavenge oxygen-free radicals in vivo and induce H 2 O 2 accumulation, thus improving the activities of SOD. In addition, the chlorophyll contents of tobacco plants were tested, and it was found that L20 could be involved in regulating the chlorophyll content of plants, promoting plant photosynthesis. Therefore, flavonol derivatives containing benzothiazole have certain antiviral activity and could be used as potential antiviral agents to control plant viruses. 4 Materials and methods 4.1 Instruments and chemicals The melting point measurements were obtained by using the X-4B melting point instrument (Shanghai INESA Co., Ltd., Shanghai, China) without calibration. NMR spectral characterization data were obtained using a JEOL-ECX500 NMR instrument with deuterated dimethylsulfoxide as the solvent (Tokyo, Japan). High resolution mass spectra (HRMS) were gained through a Thermo Scientific Q Exactive hybrid quadrupole mass spectrometer (Thermo Scientific, USA). The Kd values of the compounds against TMV-CP were determined by using NanoTemper Monolith NT.115 micro-thermophoresis (NanoTemper, Germany). The reagents and solvents used in the experiment were purchased from Shanghai Titan Chemical Co., Ltd. (Shanghai, China) and Bositai Technology Co., Ltd. (Chongqing, China). The reagents and solvents used were of analytical grade and could be put into application without further purification. 4.2 Synthesis of compounds 4.2.1. Preparation of intermediate Intermediates 1 and 2 were synthesized by the method reported[ 29 , 30 ], the detailed experimental methods were provided in the Supporting Information . Substituted 2-aminobenzothiazole (1.00 g, 6.66 mmol) and K 2 CO 3 (1.84 g, 13.32 mmol) were dissolved in 40 mL dichloromethane, stirred at room temperature for 30 min, and slowly added chloroacetyl chloride (0.64 mL, 7.99 mmol). The reaction mixture was stirred at room temperature for 2–3 h and monitored by TLC (petroleum ether: ethyl acetate = 1:1, v/v ). After the reaction was completed, a large amount of white solid, intermediate 3 (R 2 = H), was obtained by suction filtration[ 31 ]. 4.2.2. Synthesis of target compounds L1-L26 Take L1 as an example, intermediates 2 (0.6 g, 2.38 mmol) and K 2 CO 3 (0.99 g, 7.14 mmol) were dissolved in 25 mL N , N -Dimethylformamide (DMF) and returned at 100 ℃ for 30 min, then intermediate 3 (0.65 g, 2.85 mmol) was added at 100 ℃ for 3–4 h. After the reaction completed, the product was poured into ice water, and the solid was deposited. After extraction and filtration, the crude product was separated and purified by column layer analysis (petroleum ether: ethyl acetate = 6:1, v/v ) to obtain the target compound L1 . L2-L26 was obtained by reference to the above synthesis method. N-(5-bromobenzo[d]thiazol-2-yl)-2-((4-oxo-2-phenyl-4H-chromen-3-yl)oxy)acetamide ( L1 ). White solid, m.p. 212.2–213.7 ℃; yield: 43.4%. 1 H NMR (500 MHz, DMSO- d ) δ 12.65 (s, 1H, -CO- NH -), 8.22 (d, J = 2.0 Hz, 1H, Ph-H), 8.13 (dd, J = 6.5, 3.0 Hz, 2H, Ph-H), 8.09 (dd, J = 8.0, 1.5 Hz, 1H, Ph-H), 7.84–7.81 (m, 1H, Ph-H), 7.76 (d, J = 8.5 Hz, 1H, Ph-H), 7.66 (d, J = 8.5 Hz, 1H, Ph-H), 7.55–7.52 (m, 4H, Ph-H), 7.48 (dd, J = 11.5, 4.5 Hz, 1H, Ph-H), 4.91 (s, 2H, -O- CH 2 -CO-). 13 C NMR (125 MHz, DMSO- d ) δ 179.35 (s), 173.56 (s), 163.47 (s), 160.16 (s), 160.05 (s), 152.96 (s), 144.85 (s), 139.71 (s), 138.97 (s), 136.38 (s), 135.49 (s), 134.49 (s), 133.99 (s), 133.93 (s), 130.62 (s), 130.30 (s), 129.61 (s), 128.48 (s), 127.55 (s), 123.82 (s), 120.91 (s), 75.47 (s). HRMS (ESI) m/z [M + H] + calcd for C 24 H 16 BrN 2 O 4 S: 508.99882, found: 508.99969. N-(5-bromobenzo[d]thiazol-2-yl)-2-((4-oxo-2-(p-tolyl)-4H-chromen-3-yl)oxy)acetamide ( L2 ). Purple solid, m.p. >230 ℃; yield: 38.6%. 1 H NMR (500 MHz, DMSO- d ) δ 12.70 (s, 1H, -CO- NH -), 8.07 (dd, J = 8.0, 1.5 Hz, 1H, Ph-H), 8.04 (d, J = 8.5 Hz, 2H, Ph-H), 7.94–7.91 (m, 2H, Ph-H), 7.82–7.80 (m, 1H, Ph-H), 7.75 (d, J = 8.0 Hz, 1H, Ph-H), 7.49–7.46 (m, 1H, Ph-H), 7.43 (dd, J = 8.5, 2.0 Hz, 1H, Ph-H), 7.33 (s, 1H, Ph-H), 7.31 (s, 1H, Ph-H), 4.87 (s, 2H, -O- CH 2 -CO-), 2.31 (s, 3H, Ph-CH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.47 (s), 168.78 (s), 159.61 (s), 155.62 (s), 155.23 (s), 150.56 (s), 141.77 (s), 139.85 (s), 134.88 (s), 131.29 (s), 129.76 (s), 129.15 (s), 127.85 (s), 126.84 (s), 125.82 (s), 125.51 (s), 124.22 (s), 123.70 (s), 123.54 (s), 119.48 (s), 119.03 (s), 70.73 (s), 21.60 (s). HRMS (ESI) m/z [M + H] + calcd for C 25 H 18 BrN 2 O 4 S: 521.01652, found: 521.01526. N-(5-bromobenzo[d]thiazol-2-yl)-2-((2-(3-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide ( L3 ). White solid, m.p. 183.1–184.9 ℃; yield: 48.9%. 1 H NMR (500 MHz, DMSO- d ) δ 12.65 (s, 1H, -CO- NH -), 8.08 (dd, J = 8.0, 1.5 Hz, 2H, Ph-H), 7.84–7.80 (m, 1H, Ph-H), 7.77 (d, J = 8.0 Hz, 1H, Ph-H), 7.73–7.68 (m, 3H, Ph-H), 7.48 (t, J = 7.5 Hz, 1H, Ph-H), 7.46–7.41 (m, 2H, Ph-H), 7.09 (dd, J = 8.0, 2.0 Hz, 1H, Ph-H), 4.91 (s, 3H, Ph- OCH 3 ), 3.78 (s, 2H, -O- CH 2 -CO-). 13 C NMR (125 MHz, DMSO- d ) δ 174.56 (s), 168.68 (s), 159.62 (s), 158.73 (s), 155.24 (s), 155.16 (s), 147.89 (s), 140.11 (s), 134.95 (s), 133.71 (s), 131.91 (s), 130.29 (s), 128.23 (s), 127.05 (s), 125.86 (s), 125.50 (s), 123.68 (s), 122.38 (s), 122.02 (s), 121.44 (s), 119.11 (s), 117.40 (s), 114.53 (s), 70.67 (s), 55.79 (s). HRMS (ESI) m/z [M + H] + calcd for C 25 H 18 BrN 2 O 5 S: 537.01143, found: 537.01013. N-(5-bromobenzo[d]thiazol-2-yl)-2-((2-(4-fluorophenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide ( L4 ). Yellow solid, m.p. >230 ℃; yield: 50.1%. 1 H NMR (500 MHz, DMSO- d ) δ 12.68 (s, 1H, -CO- NH -), 8.22–8.19 (m, 2H, Ph-H), 8.07 (dd, J = 8.0, 1.5 Hz, 1H, Ph-H), 7.92 (dd, J = 5.0, 3.0 Hz, 2H, Ph-H), 7.83–7.80 (m, 1H, Ph-H), 7.75 (d, J = 8.0 Hz, 1H, Ph-H), 7.48 (t, J = 7.0 Hz, 1H, Ph-H), 7.43 (dd, J = 8.5, 2.0 Hz, 1H, Ph-H), 7.38–7.35 (m, 2H, Ph-H), 4.93 (s, 2H, -O- CH 2 -CO-). 13 C NMR (125 MHz, DMSO- d ) δ 174.44 (s), 168.79 (s), 164.93 (d, 1 J C−F = 248.8 Hz), 159.59 (s), 155.18 (s), 154.41 (s), 150.53 (s), 139.80 (s), 134.93 (s), 131.99 (d, 3 J C−F =8.8 Hz), 131.25 (s), 127.25 (d, 4 J C−F = 2.5 Hz), 126.83 (s), 125.50 (s), 124.20 (s), 123.69 (s), 123.52 (s), 119.48 (s), 119.03 (s), 116.32 (d, 2 J C−F = 21.3 Hz), 116.15 (s), 70.55 (s). 19 F NMR (470 MHz, DMSO- d ) δ -108.47. HRMS (ESI) m/z [M + H] + calcd for C 24 H 15 BrFN 2 O 4 S: 524.99144, found: 524.99030. N-(5-bromobenzo[d]thiazol-2-yl)-2-((2-(4-(tert-butyl)phenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide ( L5 ). White solid, m.p. 219.1–220.9 ℃; yield: 44.6%. 1 H NMR (500 MHz, DMSO- d ) δ 12.71 (s, 1H, -CO- NH- ), 8.07 (dd, J = 13.5, 5.0 Hz, 3H, Ph-H), 7.92 (d, J = 8.5 Hz, 2H, Ph-H), 7.83–7.79 (m, 1H, Ph-H), 7.74 (d, J = 8.5 Hz, 1H, Ph-H), 7.52–7.46 (m, 3H, Ph-H), 7.43 (dd, J = 8.5, 2.0 Hz, 1H, Ph-H), 4.88 (s, 2H, -O- CH 2 -CO-), 1.23 (s, 9H, Ph- C(CH 3 ) 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.44 (s), 168.72 (s), 159.58 (s), 155.61 (s), 155.23 (s), 154.49 (s), 150.54 (s), 139.83 (s), 134.88 (s), 131.27 (s), 129.02 (s), 127.90 (s), 126.82 (s), 125.97(s), 125.82(s), 125.51 (s), 124.19 (s), 123.71 (s), 123.54 (s), 119.46 (s), 119.00 (s), 70.74 (s), 35.19 (s), 31.32 (s). HRMS (ESI) m/z [M + H] + calcd for C 28 H 24 BrN 2 O 4 S: 563.06347, found: 563.06207. N - (6-chlorobenzo[d]thiazol-2-yl)-2-((4-oxo-2-phenyl-4H-chromen-3-yl)oxy)acetamide ( L6 ). Purple solid, m.p. 182.9–183.4 ℃; yield: 51.0%. 1 H NMR (500 MHz, DMSO- d ) δ 12.66 (s, 1H, -CO- NH -), 8.13 (dd, J = 6.5, 3.0 Hz, 2H, Ph-H), 8.10–8.08 (m, 2H, Ph-H), 7.84–7.81 (m, 1H, Ph-H), 7.76 (d, J = 8.5 Hz, 1H, Ph-H), 7.72 (d, J = 8.5 Hz, 1H, Ph-H), 7.55–7.53 (m, 3H, Ph-H), 7.49 (t, J = 7.5 Hz, 1H, Ph-H), 7.42 (dd, J = 8.5, 2.0 Hz, 1H, Ph-H), 4.91 (s, 2H, -O- CH 2 -CO-). 13 C NMR (125 MHz, DMSO- d ) δ 174.59 (s), 168.79 (s), 158.73 (s), 155.40 (s), 155.28 (s), 147.90 (s), 140.07 (s), 134.96 (s), 133.71 (s), 131.63 (s), 130.72 (s), 129.23 (s), 129.17 (s), 128.24 (s), 127.06 (s), 125.87 (s), 125.53 (s), 123.70 (s), 122.39 (s), 122.02 (s), 119.06 (s), 70.69 (s). HRMS (ESI) m/z [M + H] + calcd for C 24 H 16 ClN 2 O 4 S: 463.05138, found: 463.05002. N-(6-chlorobenzo[d]thiazol-2-yl)-2-((4-oxo-2-(p-tolyl)-4H-chromen-3-yl)oxy)acetamide ( L7 ). White solid, m.p. 227.8-228.5 ℃; yield: 44.6%. 1 H NMR (500 MHz, DMSO- d ) δ 12.65 (s 1H, -CO- NH -), 8.08 (d, J = 8.5 Hz, 2H, Ph-H), 8.04 (d, J = 8.0 Hz, 2H, Ph-H), 7.83–7.80 (m, 1H, Ph-H), 7.76 (d, J = 8.5 Hz, 1H, Ph-H), 7.72 (d, J = 8.5 Hz, 1H, Ph-H), 7.48 (t, J = 7.5 Hz, 1H, Ph-H), 7.43 (d, J = 8.5 Hz, 1H, Ph-H), 7.33 (d, J = 8.0 Hz, 2H, Ph-H), 4.87 (s, 2H, -O- CH 2 -CO-), 2.32 (s, 3H, Ph- CH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.51 (s), 168.76 (s), 158.75 (s), 155.68 (s), 155.24 (s), 147.92 (s), 141.78 (s), 139.88 (s), 134.89 (s), 133.73 (s), 129.77 (s), 129.15 (s), 128.23 (s), 127.85 (s), 127.05 (s), 125.82 (s), 125.52 (s), 123.70 (s), 122.39 (s), 122.01 (s), 119.02 (s), 70.79 (s), 21.60 (s). HRMS (ESI) m/z [M + H] + calcd for C 25 H 18 ClN 2 O 4 S: 477.06703, found: 477.06662. N-(6-chlorobenzo[d]thiazol-2-yl)-2-((2-(3-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide ( L8 ). Purple solid, m.p. 205.8-207.4 ℃; yield: 39.4%. 1 H NMR (500 MHz, DMSO- d ) δ 12.65 (s, 1H, -CO- NH -), 8.09–8.07 (m, 2H, Ph-H), 7.84–7.80 (m, 1H, Ph-H), 7.77 (d, J = 8.0 Hz, 1H, Ph-H), 7.72 (d, J = 8.5 Hz, 1H, Ph-H), 7.69–7.68 (m, 2H, Ph-H), 7.48 (d, J = 7.0 Hz, 1H, Ph-H), 7.44–7.41 (m, 2H, Ph-H), 7.09 (dd, J = 8.0, 2.0 Hz, 1H, Ph-H), 4.91 (s, 2H, -O- CH 2 -CO-), 3.78 (s, 3H, Ph-OCH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.08 (s), 168.32 (s), 159.14 (s), 158.45 (s), 154.76 (s), 154.66 (s), 147.44 (s), 139.64 (s), 134.47 (s), 133.25 (s), 131.45 (s), 129.81 (s), 127.67 (s), 126.53 (s), 125.39 (s), 125.02 (s), 123.21 (s), 121.85 (s), 121.52 (s), 120.96 (s), 118.64 (s), 116.93 (s), 114.04 (s), 70.23 (s), 55.31 (s). HRMS (ESI) m/z [M + H] + calcd for C 25 H 18 ClN 2 O 5 S: 493.06195, found: 493.06088. N-(6-chlorobenzo[d]thiazol-2-yl)-2-((2-(4-fluorophenyl)-4-oxo-4H-chromen-3-yl)oxy) acetamide ( L9 ). White solid, m.p. >230 ℃; yield: 41.9%. 1 H NMR (500 MHz, DMSO- d ) δ 12.59 (s, 1H, -CO- NH -), 8.16 (dd, J = 8.5, 6.0 Hz, 1H, Ph-H), 8.02 (d, J = 6.0 Hz, 2H, Ph-H), 8.01–7.93 (m, 1H, Ph-H), 7.79–7.75 (m, 1H, Ph-H), 7.71 (dd, J = 16.0, 8.5 Hz, 1H, Ph-H), 7.66 (d, J = 8.5 Hz, 1H, Ph-H), 7.43 (t, J = 7.5 Hz, 1H, Ph-H), 7.40–7.27 (m, 3H, Ph-H), 4.95–4.89 (m, 2H, -O- CH 2 -CO-). 13 C NMR (125 MHz, DMSO- d ) δ , 174.04 (s), 168.28 (s), 164.47 (d, 1 J C−F = 248.6 Hz), 158.24 (s), 54.71 (s), 153.98 (s), 147.41 (s), 139.35 (s), 134.46 (s), 133.22 (s), 131.51(d, 3 J C−F = 8.8 Hz), 127.77 (s), 126.57 (s), 125.39 (s), 125.03 (s), 124.87 (s), 123.21 (s), 121.52 (s), 118.55 (s), 115.86 (d, 2 J C−F = 21.6 Hz), 70.11 (s). 19 F NMR (476 MHz, DMSO- d ) δ -108.46. HRMS (ESI) m/z [M + H] + calcd for C 24 H 15 ClFN 2 O 4 S:481.04196, found: 481.04123. 2-((2-(4-(tert-butyl)phenyl)-4-oxo-4H-chromen-3-yl)oxy)-N-(6-chlorobenzo[d]thiazol-2-yl)acetamide ( L10 ). White solid, m.p. 171.5–172.4 ℃; yield: 39.5%. 1 H NMR (500 MHz, DMSO- d ) δ 12.66 (s, 1H, -CO- NH -), 8.09–8.06 (m, 3H, Ph-H), 8.05–8.04 (m, 1H, Ph-H), 7.81–7.79 (m, 1H, Ph-H), 7.74 (d, J = 8.0 Hz, 1H, Ph-H), 7.71 (d, J = 8.5 Hz, 1H, Ph-H), 7.53–7.50 (m, 2H, Ph-H), 7.49–7.46 (m, 1H, Ph-H), 7.43–7.41 (m, 1H, Ph-H), 4.88 (s, 2H, -O- CH 2 -CO-), 1.23 (s, 9H, Ph- C(CH 3 ) 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.47 (s), 168.70 (s), 158.71 (s), 155.65 (s), 155.24 (s), 154.51 (s), 147.88 (s), 139.86 (s), 134.89 (s), 133.70 (s), 129.96 (s), 129.01 (s), 128.23 (s), 127.88 (s), 127.04 (s), 125.98 (s), 125.51 (s), 123.70 (s), 122.38 (s), 121.99 (s), 119.00 (s), 70.78 (s), 35.19 (s), 31.31 (s). HRMS (ESI) m/z [M + H] + calcd for C 28 H 24 ClN 2 O 4 S: 519.11398, found: 519.11267. N-(6-chlorobenzo[d]thiazol-2-yl)-2-((2-(2-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide (L11). Yellow solid, m.p. >230 ℃; yield: 43.8%. 1 H NMR (500 MHz, DMSO- d ) δ 12.43 (s, 1H, -CO- NH -), 8.10–8.03 (m, 2H, Ph-H), 7.76 (t, J = 7.0 Hz, 1H, Ph-H), 7.67 (d, J = 8.5 Hz, 1H, Ph-H), 7.62 (d, J = 8.5 Hz, 1H, Ph-H), 7.53–7.50 (m, 1H, Ph-H), 7.47–7.44 (m, 2H, Ph-H), 7.38 (dd, J = 8.5, 2.0 Hz, 1H, Ph-H), 7.10 (d, J = 8.5 Hz, 1H, Ph-H), 7.01 (t, J = 7.5 Hz, 1H, Ph-H), 4.73 (s, 2H, -O- CH 2 -CO-), 3.71 (s, 3H, Ph- OCH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 173.71 (s), 168.21 (s), 158.25 (s), 156.88 (s), 155.53 (s), 155.23 (s), 147.42 (s), 140.22 (s), 134.41 (s), 133.23 (s), 132.46 (s), 130.61 (s), 127.73 (s), 126.57 (s), 125.40 (s), 125.12 (s), 123.51 (s), 121.89 (s), 121.54 (s), 120.33 (s), 119.16 (s), 118.57 (s), 111.79 (s), 70.46 (s), 55.74 (s). HRMS (ESI) m/z [M + H] + calcd for C 25 H 18 ClN 2 O 5 S: 493.06195, found: 493.06256. N-(benzo[d]thiazol-2-yl)-2-((4-oxo-2-phenyl-4H-chromen-3-yl)oxy)acetamide ( L12 ). Yellow solid, m.p. 201.9–203.8 ℃; yield: 46.2%. 1 H NMR (500 MHz, DMSO- d ) δ 12.57 (s, 1H, -CO- NH -), 8.09 (m, 3H, Ph-H), 7.94 (d, J = 8.0 Hz, 1H, Ph-H), 7.83–7.80 (m, 1H, Ph-H), 7.74 (dd, J = 13.5, 8.0 Hz, 2H, Ph-H), 7.55–7.53 (m, 3H, Ph-H), 7.48 (t, J = 7.5 Hz, 1H, Ph-H), 7.40 (t, J = 7.5 Hz, 1H, Ph-H, 7.27 (t, J = 7.5 Hz, 1H, Ph-H), 4.99 (m, 2H, -O- CH 2 -CO-). 13 C NMR (125 MHz, DMSO- d ) δ 174.63 (s), 168.59 (s), 165.96 (s), 157.86 (s), 155.43 (s), 155.28 (s), 140.10 (s), 134.96 (s), 131.64 (s), 130.72 (s), 130.02 (s), 129.42 (s), 129.22 (s), 126.73 (s), 125.87 (s), 125.54 (s), 124.22 (s), 123.70 (s), 122.30 (s), 121.17 (s), 119.06 (s), 70.74 (s). HRMS (ESI) m/z [M + H] + calcd for C 24 H 17 N 2 O 4 S: 429.09035, found: 429.08932. N-(benzo[d]thiazol-2-yl)-2-((4-oxo-2-(p-tolyl)-4H-chromen-3-yl)oxy)acetamide ( L13 ). White solid, m.p. >230 ℃; yield: 33.4%. 1 H NMR (500 MHz, DMSO- d ) δ 12.57 (s, 1H, -CO- NH -), 8.09 (d, J = 8.0 Hz, 1H, Ph-H), 8.06 (d, J = 8.0 Hz, 2H, Ph-H), 7.95 (d, J = 8.0 Hz, 1H, Ph-H), 7.82 (t, J = 7.5 Hz, 1H, Ph-H), 7.75 (dd, J = 16.5, 8.0 Hz, 2H, Ph-H), 7.49 (t, J = 7.5 Hz, 1H, Ph-H), 7.41 (t, J = 7.5 Hz, 1H, Ph-H), 7.34 (d, J = 8.0 Hz, 2H, Ph-H), 7.28 (t, J = 7.5 Hz, 1H, Ph-H), 4.87 (s, 2H, -O- CH 2 -CO-), 2.33 (s, 3H, Ph- CH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.53 (s), 168.54 (s), 157.85 (s), 155.66 (s), 155.25 (s), 149.02 (s), 141.79 (s), 139.91 (s), 134.89 (s), 132.02 (s), 129.79 (s), 129.15 (s), 127.87 (s), 126.71 (s), 125.83 (s), 125.52 (s), 124.21 (s), 123.71 (s), 122.30 (s), 121.19 (s), 119.04 (s), 70.80 (s), 21.61 (s). HRMS (ESI) m/z [M + H] + calcd for C 25 H 19 N 2 O 4 S: 443.10600, found: 443.10461. N-(benzo[d]thiazol-2-yl)-2-((2-(3-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide ( L14 ). White solid, m.p. 191.5–192.0 ℃; yield: 35.6%. 1 H NMR (500 MHz, DMSO- d ) δ 12.52 (s, 1H, -CO- NH -), 8.07 (d, J = 6.5 Hz, 1H, Ph-H), 7.92 (d, J = 7.0 Hz, 1H, Ph-H), 7.80–7.74 (m, 2H, Ph-H), 7.68 (s, 3H, Ph-H), 7.51–7.36 (m, 3H, Ph-H), 7.25 (s, 1H, Ph-H), 7.07 (d, J = 6.5 Hz, 1H, Ph-H), 4.89 (s, 2H, -O- CH 2 -CO-), 3.76 (s, 3H, Ph- OCH 3 ). 13 C NMR (125 MHz, DMSO) δ 174.53 (s), 168.42 (s), 159.59 (s), 157.79 (s), 155.20 (s), 155.11 (s), 148.94 (s), 140.09 (s), 134.88 (s), 131.96 (s), 131.88 (s), 130.25 (s), 126.65 (s), 125.81 (s), 125.45 (s), 124.15 (s), 123.64 (s), 122.25 (s), 121.38 (s), 121.12 (s), 119.06 (s), 117.37 (s), 114.47 (s), 70.65 (s), 55.74 (s). HRMS (ESI) m/z [M + H] + calcd for C 25 H 19 N 2 O 5 S: 459.10092, found: 459.10016. N-(benzo[d]thiazol-2-yl)-2-((2-(4-fluorophenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide ( L15 ). White solid, m.p. 196.7–198.8 ℃; yield: 36.5%. 1 H NMR (500 MHz, DMSO- d ) δ 12.52 (s, 1H, -CO- NH -), 8.22–8.18 (m, 2H, Ph-H), 8.06 (dd, J = 8.0, 1.5 Hz, 1H, Ph-H), 7.91 (d, J = 8.0 Hz, 1H, Ph-H), 7.79–7.77 (m, 1H, Ph-H), 7.74–7.72 (m, 1H, Ph-H), 7.70 (d, J = 8.0 Hz, 1H, Ph-H), 7.47–7.44 (m, 1H, Ph-H), 7.41–7.36 (m, 2H, Ph-H), 7.35–7.33 (m, 1H, Ph-H), 7.27–7.23 (m, 1H, Ph-H), 4.91 (s, 2H, -O- CH 2 -CO-). 13 C NMR (125 MHz, DMSO- d ) δ 174.50 (s), 168.54 (s), 164.95 (d, 1 J C−F = 248.8 Hz), 157.84 (s), 155.21 (s), 154.46 (s), 149.01 (s), 139.87 (s), 134.94 (s), 132.00 (d, 3 J C−F = 8.8 Hz), 127.27 (d, 4 J C−F = 2.5 Hz), 126.71 (s), 125.87 (s), 125.52 (s), 124.20 (s), 123.71 (s), 122.29 (s), 121.18 (s), 119.05 (s), 116.35(d, 2 J C−F = 21.3 Hz), 70.61 (s). 19 F NMR (470 MHz, DMSO- d ) δ -108.45. HRMS (ESI) m/z [M + H] + calcd for C 24 H 16 FN 2 O 4 S: 447.08093, found: 447.07941. N-(benzo[d]thiazol-2-yl)-2-((2-(4-(tert-butyl)phenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide ( L16 ). Yellow solid, m.p. 182.9–184.4 ℃; yield: 32.2%. 1 H NMR (500 MHz, DMSO- d ) δ 12.92 (s, 1H, -CO- NH -), 8.13–8.11 (m, 2H, Ph-H), 7.99 (dd, J = 8.0, 1.5 Hz, 1H, Ph-H), 7.90 (t, J = 8.0 Hz, 2H, Ph-H), 7.67 (d, J = 8.0 Hz, 2H, Ph-H), 7.48–7.46 (m, 2H, Ph-H), 7.41–7.34 (m, 2H, Ph-H), 7.34 (dd, J = 11.5, 4.0 Hz, 1H, Ph-H), 4.98 (s, 2H, -O- CH 2 -CO-), 1.21 (s, 9H, Ph- C(CH 3 ) 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 178.18 (s), 174.24 (s), 167.32 (s), 155.05 (s), 154.72 (s), 154.18 (s), 139.49 (s), 137.11 (s), 134.50 (s), 128.95 (s), 128.30 (s), 126.78 (s), 125.84 (s), 125.43 (s), 124.77 (s), 124.32 (s), 123.82 (s), 122.31 (s), 118.86 (s), 113.17 (s), 72.46 (s), 35.13 (s), 31.31 (s). HRMS (ESI) m/z [M + H] + calcd for C 28 H 25 N 2 O 4 S: 485.15295, found: 485.15186. N-(benzo[d]thiazol-2-yl)-2-((2-(4-chlorophenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide ( L17 ). Yellow solid, m.p. 210.9–212.1 ℃; yield: 37.9%. 1 H NMR (500 MHz, DMSO- d ) δ 12.53 (s, 1H, -CO- NH -), 8.17 (d, J = 8.5 Hz, 2H, Ph-H), 8.08 (dd, J = 8.0, 1.5 Hz, 1H, Ph-H), 7.94 (d, J = 8.0 Hz, 1H, Ph-H), 7.84–7.80 (m, 1H, Ph-H), 7.75 (d, J = 8.5 Hz, 1H, Ph-H), 7.72 (d, J = 8.0 Hz, 1H, Ph-H), 7.60 (s, 1H, Ph-H), 7.58 (s, 1H, Ph-H), 7.50–7.46 (m, 1H, Ph-H), 7.40 (dd, J = 11.0, 4.0 H, 1H, Ph-Hz), 7.29–7.26 (m, 1H, Ph-H), 4.94 (s, 2H, -O- CH 2 -CO-). 13 C NMR (125 MHz, DMSO- d ) δ 174.47 (s), 168.49 (s), 157.83 (s), 155.20 (s), 154.13 (s), 149.00 (s), 140.15 (s), 136.33 (s), 134.99 (s), 132.01(s), 131.07 (s), 129.60 (s), 129.23 (s), 126.70 (s), 125.89 (s), 125.52 (s), 124.20 (s), 123.72 (s), 122.29 (s), 121.17 (s), 119.05 (s), 70.61 (s). HRMS (ESI) m/z [M + H] + calcd for C 24 H 16 ClN 2 O 4 S: 463.05138, found: 463.05011. N-(4-methylbenzo[d]thiazol-2-yl)-2-((4-oxo-2-phenyl-4H-chromen-3-yl)oxy)acetamide ( L18 ). Yellow solid, m.p. 184.2–185.4 ℃; yield: 39.5%. 1 H NMR (500 MHz, DMSO- d ) δ 12.56 (s, 1H, -CO- NH -), 8.16–8.13 (m, 2H, Ph-H), 8.08 (dd, J = 8.0, 1.5 Hz, 1H, Ph-H), 7.83–7.80 (m, 1H, Ph-H), 7.77–7.74 (m, 2H, Ph-H), 7.53 (dd, J = 5.5, 2.0 Hz, 3H, Ph-H), 7.48 (dd, J = 11.5, 4.5 Hz, 1H, Ph-H), 7.22 (d, J = 7.0 Hz, 1H, Ph-H), 7.17 (d, J = 7.5 Hz, 1H, Ph-H), 4.93 (s, 2H, -O- CH 2 -CO-), 2.53 (s, 3H, Ph- CH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 173.96 (s), 167.89 (s), 156.49 (s), 154.78(s), 154.74(s), 147.60 (s), 139.48 (s), 134.42 (s), 131.10 (s), 130.32 (s), 129.98 (s), 129.54 (s), 128.76 (s), 128.67 (s), 126.71 (s), 125.35 (s), 125.04 (s), 123.67 (s), 123.28 (s), 119.19 (s), 118.58 (s), 69.90 (s), 18.01 (s). HRMS (ESI) m/z [M + H] + calcd for C 25 H 19 N 2 O 4 S: 443.10600, found: 443.10471. N-(4-methylbenzo[d]thiazol-2-yl)-2-((4-oxo-2-(p-tolyl)-4H-chromen-3-yl)oxy)acetamide ( L19 ). Yellow solid, m.p. 158.8–160.3 ℃; yield: 44.3%. 1 H NMR (500 MHz, DMSO- d ) δ 8.08–8.04 (m, 3H, Ph-H), 7.78 (t, J = 7.5 Hz, 1H, Ph-H), 7.73 (d, J = 8.5 Hz, 1H, Ph-H), 7.65 (d, J = 7.5 Hz, 1H, Ph-H), 7.45 (t, J = 7.5 Hz, 1H, Ph-H), 7.30 (d, J = 8.0 Hz, 2H, Ph-H), 7.14 (d, J = 7.0 Hz, 1H, Ph-H), 7.08 (t, J = 7.5 Hz, 1H, Ph-H), 4.82 (s, 2H, -O- CH 2 -CO-), 2.48 (s, 3H, Ph- CH 3 ), 2.29 (s, 3H, Ph- CH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.39 (s), 155.18 (s), 148.44 (s), 141.59 (s), 134.74 (s), 131.89 (s), 129.72 (s), 129.16 (s), 128.04 (s), 126.79 (s), 125.71 (s), 125.49 (s), 123.79 (s), 119.43 (s), 118.99 (s), 70.99 (s), 21.57 (s), 18.54 (s). HRMS (ESI) m/z [M + H] + calcd for C 26 H 21 N 2 O 4 S: 457.12165, found: 457.12039. 2-((2-(3-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)-N-(4-methylbenzo[d]thiazol-2-yl)acetamide ( L20 ). White solid, m.p. 165.5-166.9 ℃; yield: 41.0%. 1 H NMR (500 MHz, DMSO- d ) δ 12.54 (s, 1H, -CO- NH -), 8.07 (d, J = 8.0 Hz, 1H, Ph-H), 7.81 (t, J = 7.5 Hz, 1H, Ph-H), 7.76–7.72 (m, 2H, Ph-H), 7.69 (d, J = 8.0 Hz, 2H, Ph-H), 7.46 (d, J = 7.5 Hz, 1H, Ph-H), 7.43 (t, J = 8.0 Hz, 1H, Ph-H), 7.21 (d, J = 7.0 Hz, 1H, Ph-H), 7.16 (t, J = 7.0 Hz, 1H, Ph-H), 7.07 (d, J = 7.5 Hz, 1H, Ph-H), 4.91 (s, 2H, -O- CH 2 -CO-), 3.77 (s, 3H, Ph- OCH 3 ), 2.52 (s, 3H, Ph- CH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.44 (s), 168.26 (s), 159.60 (s), 156.93 (s), 155.21 (s), 155.04 (s), 148.03 (s), 139.99 (s), 134.89 (s), 131.95 (s), 131.64 (s), 130.46 (s), 130.27 (s), 127.18 (s), 125.82 (s), 125.47 (s), 124.17 (s), 123.71 (s), 121.42 (s), 119.64 (s), 119.07 (s), 117.36 (s), 114.51 (s), 70.40 (s), 55.76 (s), 18.46 (s). HRMS (ESI) m/z [M + H] + calcd for C 26 H 21 N 2 O 5 S: 473.11657, found: 473.11505. 2-((2-(4-fluorophenyl)-4-oxo-4H-chromen-3-yl)oxy)-N-(4-methylbenzo[d]thiazol-2-yl)acetamide ( L21 ). White solid, m.p. 200.4–201.8 ℃; yield: 51.2%. 1 H NMR (500 MHz, DMSO- d ) δ 12.55 (s, 1H, -CO- NH -), 8.23 (dd, J = 7.5, 5.5 Hz, 2H, Ph-H), 8.07 (d, J = 8.0 Hz, 1H, Ph-H), 7.81 (t, J = 7.5 Hz, 1H, Ph-H), 7.76–7.72 (m, 2H, Ph-H), 7.47 (t, J = 7.5 Hz, 1H, Ph-H), 7.36 (t, J = 8.5 Hz, 2H, Ph-H), 7.21 (d, J = 7.0 Hz, 1H, Ph-H), 7.16 (t, J = 7.5 Hz, 1H, Ph-H), 4.95 (s, 2H, -O- CH 2 -CO-), 2.53 (s, 3H, Ph- CH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.32 (s), 168.34 (s), 164.91(d, 1 J C−F = 248.8 Hz), 156.95 (s), 155.17 (s), 154.28 (s), 148.07 (s), 139.72 (s), 134.87 (s), 131.99(d, 3 J C − F = 8.8 Hz), 131.65 (s), 130.45 (s), 127.17 (s), 125.82 (s), 125.49 (s), 124.13 (s), 123.75 (s), 119.65 (s), 119.03 (s), 116.29(d, 2 J C−F = 21.3 Hz), 116.12 (s), 70.30 (s), 18.48 (s). 19 F NMR (470 MHz, DMSO- d ) δ -108.58. HRMS (ESI) m/z [M + H] + calcd for C 25 H 18 FN 2 O 4 S: 461.09658, found: 461.09515. 2-((2-(4-(tert-butyl)phenyl)-4-oxo-4H-chromen-3-yl)oxy)-N-(4-methylbenzo[d]thiazol-2-yl)acetamide ( L22 ). Yellow solid, m.p. 180.0-181.6 ℃; yield: 45.9%. 1 H NMR (500 MHz, DMSO- d ) δ 12.57 (s, 1H, -CO- NH -), 8.07–8.04 (m, 3H, Ph-H), 7.80–7.76 (m, 1H, Ph-H), 7.71 (dd, J = 7.5, 4.5 Hz, 2H, Ph-H), 7.50–7.47 (m, 2H, Ph-H), 7.45 (dd, J = 11.0, 4.0 Hz, 1H, Ph-H), 7.19 (d, J = 7.0 Hz, 1H, Ph-H), 7.16–7.13 (m, 1H, Ph-H), 4.89 (s, 2H, 2H-O- CH 2 -CO-), 2.52 (s, 3H, Ph-CH 3 ), 1.20 (s, 9H, Ph- C(CH 3)3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.30 (s), 168.23 (s), 156.93 (s), 155.46 (s), 155.18 (s), 154.41 (s), 148.06 (s), 139.71 (s), 134.77 (s), 131.66 (s), 130.43 (s), 129.95 (s), 128.99 (s), 127.93 (s), 127.14 (s), 125.90 (s), 125.47 (s), 124.12 (s), 123.74 (s), 119.60 (s), 118.94 (s), 70.47 (s), 35.13 (s), 31.27 (s), 18.48 (s). HRMS (ESI) m/z [M + H] + calcd for C 29 H 27 N 2 O 4 S: 499.16860, found: 499.16733. 2-((2-(4-chlorophenyl)-4-oxo-4H-chromen-3-yl)oxy)-N-(4-methylbenzo[d]thiazol-2-yl)acetamide ( L23 ). Yellow solid, m.p. 201.9–203.6 ℃; yield: 52.8%. 1 H NMR (500 MHz, DMSO- d ) δ 12.53 (s, 1H,-CO- NH -), 8.17 (d, J = 8.5 Hz, 2H, Ph-H), 8.07 (d, J = 8.0 Hz, 1H, Ph-H), 7.82 (t, J = 7.5 Hz, 1H, Ph-H), 7.76–7.72 (m, 2H, Ph-H), 7.58 (d, J = 8.5 Hz, 2H, Ph-H), 7.48 (t, J = 7.5 Hz, 1H, Ph-H), 7.21 (d, J = 7.0 Hz, 1H, Ph-H), 7.16 (t, J = 7.5 Hz, 1H, Ph-H), 4.94 (s, 2H, -O- CH 2 -CO-), 2.52 (s, 3H, Ph-CH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.33 (s), 168.31 (s), 156.95 (s), 155.18 (s), 154.04 (s), 148.05 (s), 140.01 (s), 136.27 (s), 134.97 (s), 131.63 (s), 131.09 (s), 130.45 (s), 129.64 (s), 129.19 (s), 127.18 (s), 125.88 (s), 125.51 (s), 124.16 (s), 123.76 (s), 119.65 (s), 119.05 (s), 70.34 (s), 18.48 (s). HRMS (ESI) m/z [M + H] + calcd for C 25 H 18 ClN 2 O 4 S: 477.06703, found: 477.06583. N-(6-methoxybenzo[d]thiazol-2-yl)-2-((4-oxo-2-phenyl-4H-chromen-3-yl)oxy)acetamide (L24) . Yellow solid, m.p. 149.1–150.9 ℃; yield: 48.5%. 1 H NMR (500 MHz, DMSO- d ) δ 12.44 (s, 1H, -CO- NH -), 8.13 (dd, J = 6.5, 3.0 Hz, 2H, Ph-H), 8.09 (dd, J = 8.0, 1.5 Hz, 1H, Ph-H), 7.82–7.81 (m, 1H, Ph-H), 7.76 (d, J = 8.0 Hz, 1H, Ph-H), 7.62 (d, J = 9.0 Hz, 1H, Ph-H), 7.55–7.52 (m, 4H, Ph-H), 7.49 (dd, J = 11.0, 4.0 Hz, 1H, Ph-H), 6.99 (dd, J = 9.0, 2.5 Hz, 1H, Ph-H), 4.88 (s, 2H, -O- CH 2 -CO-), 3.76 (s, 3H, Ph- OCH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.64(s), 168.26(s), 156.72(s), 155.74(s), 155.43(s), 155.39(s), 143.08(s), 140.13(s), 134.95(s), 133.33(s), 131.64(s), 130.72(s), 129.22(s), 125.87(s), 125.54(s), 123.70(s), 121.80(s), 119.06(s), 115.52(s), 105.22(s), 70.72(s). HRMS (ESI) m/z [M + H] + calcd for C 25 H 19 N 2 O 5 S: 459.10092, found: 459.09961. N-(6-methoxybenzo[d]thiazol-2-yl)-2-((4-oxo-2-(p-tolyl)-4H-chromen-3-yl)oxy)acetamide ( L25 ). Yellow solid, m.p. 172.4–174.3 ℃; yield: 36.5%. 1 H NMR (500 MHz, DMSO- d ) δ 12.44 (s, 1H, -CO- NH -), 8.08 (d, J = 7.0 Hz, 1H, Ph-H), 8.04 (d, J = 8.0 Hz, 2H, Ph-H), 7.83–7.79 (m, 1H, Ph-H), 7.75 (d, J = 8.5 Hz, 1H, Ph-H), 7.62 (d, J = 9.0 Hz, 1H, Ph-H), 7.54–7.46 (m, 2H, Ph-H), 7.33 (d, J = 8.0 Hz, 2H, Ph-H), 6.99 (dd, J = 8.5, 2.5 Hz, 1H, Ph-H), 4.83 (s, 2H, -O- CH 2 -CO-), 3.76 (s, 3H, Ph- OCH 3 ), 2.32 (s, 3H, Ph- CH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.56 (s), 168.22 (s), 156.73 (s), 155.70 (s), 155.24 (s), 141.80 (s), 139.93 (s), 134.89 (s), 129.80 (s), 129.13 (s), 127.85 (s), 125.82 (s), 125.52 (s), 121.81 (s), 119.03 (s), 115.52 (s), 105.23 (s), 70.80 (s), 56.14 (s), 21.61 (s). HRMS (ESI) m/z [M + H] + calcd for C 26 H 21 N 2 O 5 S: 473.11657, found: 473.11581. N-(6-methoxybenzo[d]thiazol-2-yl)-2-((2-(3-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide (L26) . White solid, m.p. 160.3–161.5 ℃; yield: 36.4%. 1 H NMR (500 MHz, DMSO- d ) δ 12.42 (s, 1H, -CO- NH -), 8.11–8.06 (m, 1H, Ph-H ), 7.82 (dd, J = 11.0, 4.0 Hz, 1H, Ph-H), 7.76 (d, J = 8.5 Hz, 1H, Ph-H), 7.69 (d, J = 1.0 Hz, 1H, Ph-H), 7.68 (s, 1H, Ph-H), 7.62 (d, J = 9.0 Hz, 1H, Ph-H), 7.53 (d, J = 2.0 Hz, 1H, Ph-H), 7.48 (t, J = 6.0 Hz, 1H, Ph-H), 7.45 (dd, J = 13.5, 5.5 Hz, 1H, Ph-H), 7.12–7.07 (m, 1H, Ph-H), 6.99 (dd, J = 8.5, 2.5 Hz, 1H, Ph-H), 4.88 (s, 2H, -O- CH 2 -CO-), 3.79 (s, 3H, Ph- OCH 3 ), 3.76 (s, 3H, Ph- OCH 3 ). 13 C NMR (125 MHz, DMSO- d ) δ 174.61 (s), 168.15 (s), 159.65 (s), 156.72 (s), 155.74 (s), 155.25 (s), 155.18 (s), 143.09 (s), 140.17 (s), 134.93 (s), 133.34 (s), 131.92 (s), 130.31 (s), 125.86 (s), 125.51 (s), 123.68 (s), 121.79 (s), 121.42 (s), 119.10 (s), 117.44 (s), 115.51 (s), 114.50 (s), 105.23 (s), 70.69 (s), 56.13 (s), 55.80 (s). HRMS (ESI) m/z [M + H] + calcd for C 26 H 21 N 2 O 6 S: 489.11148, found: 489.11078. 4.3 In vivo antiviral activity According to literature reports[ 32 , 33 , 34 ], L1-L26 were selected as the experimental objects for in vivo anti-virus testing using the semi-leaf blight method, with dimethyl sulfoxide (DMSO) solution as the negative control and commercial NNM as the positive control. The tobaccos treated were cultivated in an artificial climate chamber (28 ℃) for 2–3 d. When spots appear on the leaves, the number of spots on both sides is counted and the inhibition rate is calculated. Each drug was repeated three times. Specific experimental methods were described in the Supporting Information . 4.4 Microscale thermophoresis experiment The modes of binding of the target compounds to tobacco mosaic virus capsid proteins (TMV-CP) and the affinity of intermolecular interactions were investigated using MST assays. The binding affinity of L20 and L23 to TMV-CP were tested with reference to the methodology reported in the literature[ 35 , 36 ], and the commercial drug NNM was used as a positive control. The details of the experimental methods were described in the Supporting Information . 4.5 Molecular docking experiment TMV-CP not only has the function of protecting nucleic acid from degradation, but also has the function of assisting TMV long-distance transport, determining the host range and participating in nucleic acid replication. TMV-CP is often used as a potential target in the study of antiviral agents. Utilizing molecular docking simulations for predicting interactions between ligand compounds and receptor proteins to validate their binding affinity. Following established methodology detailed in literature reports[ 37 , 38 ], molecular docking simulations involving L20 and NNM with TMV-CP were conducted utilizing. Specific experimental methodologies were outlined within Supporting Information . 4.6 MDA content test Previous studies have reported that the content of MDA can reflect the degree of membrane damages in tobacco leaves infected by TMV[ 39 , 40 ]. The healthy, uniformly sized tobacco leaves were selected as the experimental subjects. The experiment was set up with four different treatments ( CK , L20 , TMV , and TMV + L20) , the whole leaves were induced with 500 µg/mL L20 , and 0.5% DMSO to obtain the groups CK and L20 ; the entire leaf was infected with 500-fold diluted virus liquid to obtain TMV group; the entire leaf was treated with 500 µg/mL L20 first, and then infected with 500-fold diluted virus liquid after 24 h to obtain TMV + L20 . Each treatment had 4 tobacco plants. Samples were collected at intervals of 1, 3, 5 and 7 d. The MDA content was determined by liquid nitrogen grinding and following the instructions in the assay kit. 4.7 SOD activity measurement According to literature reports[ 18 , 41 ], the SOD activity was determined in the leaves after the L20 treatment, with the same four treatments as the MDA content determination experiment, 0.1 g of leaf tissue was weighed after the leaf veins were removed, and the SOD activity was determined following the instructions in the assay kit. 4.8 In vivo chlorophyll content test Chlorophyll is one of the most important pigments related to photosynthesis, and its content is closely related to the health of the plant. According to the reported method[ 42 ], the change in chlorophyll content in the leaves after the L20 treatment was determined, with the same treatment and sampling steps as the MDA content determination experiment. When cells die, chlorophyll was released from the chloroplasts. Free chlorophyll is highly unstable and can be broken down by light, acid, alkali, oxygen, oxidants, etc. Therefore, leaf green content should be determined immediately after leaf sampling. Specific experimental methodologies were outlined within Supporting Information . Declarations Acknowledgement The authors gratefully acknowledge the Key Research and Development Program of Hainan Province (No. ZDYF2024XDNY202), the Science Foundation of Guizhou Province (No. ZK2024008), Chinese Academy of Tropical Agricultural Sciences for Science and Technology Innovation Team of National Tropical Agricultural Science Center (No. CATASCXTD202410). The appendix: Supplementary material The Supporting Information includes the characterization data of the target compound, NMR and HRMS spectra, and the detailed operation steps of studying the target compound matrix. 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Int J Biol Macromol 17:1133–1139. https://doi.org/10.1016/j.ijbiomac.2018.06.031 Xing L, Mao P, He BC, Qin YS, Meng KN, Zeng W, Sun ZL, Xue W (2023) Design, synthesis, and antiviral activities of myricetin derivatives containing phenoxypyridine. J Saudi Chem Soc 27(6):101751. https://doi.org/10.1016/j.jscs.2023.101751 List of Graphical abstract, Scheme1 and Figure Titles Scheme Scheme 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Onlinefloatimage3.png Scheme 1 Schematic representation of the synthesis of target compounds L1-L26. floatimage1.jpeg Graphical Abstract Supportinginformation.doc 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. 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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-5025191","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":360619331,"identity":"fa4bc54d-2aab-4c55-b902-4d0372d9c076","order_by":0,"name":"Jiao Tian","email":"","orcid":"","institution":"Center for R\u0026D of Fine Chemicals of Guizhou University","correspondingAuthor":false,"prefix":"","firstName":"Jiao","middleName":"","lastName":"Tian","suffix":""},{"id":360619332,"identity":"4cba57f8-2338-4e39-888e-97c392df5571","order_by":1,"name":"Chunmei Hu","email":"","orcid":"","institution":"Center for R\u0026D of Fine Chemicals of Guizhou University","correspondingAuthor":false,"prefix":"","firstName":"Chunmei","middleName":"","lastName":"Hu","suffix":""},{"id":360619333,"identity":"07cc2aef-8cf7-47e5-a5a1-5203d495d736","order_by":2,"name":"Yuhong Wang","email":"","orcid":"","institution":"Center for R\u0026D of Fine Chemicals of Guizhou University","correspondingAuthor":false,"prefix":"","firstName":"Yuhong","middleName":"","lastName":"Wang","suffix":""},{"id":360619334,"identity":"af9a8d46-b778-429e-99a3-5501e45179fa","order_by":3,"name":"Qing Zhou","email":"","orcid":"","institution":"Center for R\u0026D of Fine Chemicals of Guizhou University","correspondingAuthor":false,"prefix":"","firstName":"Qing","middleName":"","lastName":"Zhou","suffix":""},{"id":360619335,"identity":"e01917f2-3bee-4dcc-a648-1bd6ab899213","order_by":4,"name":"Xingping Luo","email":"","orcid":"","institution":"Center for R\u0026D of Fine Chemicals of Guizhou 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University","correspondingAuthor":false,"prefix":"","firstName":"Da","middleName":"","lastName":"Liu","suffix":""},{"id":360619340,"identity":"7e9d4de5-3c12-4b33-83bd-4b03917683d5","order_by":8,"name":"Wei Xue","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsklEQVRIiWNgGAWjYLCCDxDKgHgdjDNI1sLMQ5IWgxs5ho9tftUlNrA3b5NgqLlDhJYzZ4yNc/vYEht4jpVJMBx7RliL2fEeM+ncHp7EBokcMwnGhsNEaDnMY/7bskcisUH+DbFagLYwM/wwANrCQ6QW+zPHiiV7GxKM23jSii0SjhGhRXJG8sYPP/7UyfazH95440MNEVrAgLGNgYENxEggUgMQ/CFe6SgYBaNgFIxAAAAdsjbCMN1BAwAAAABJRU5ErkJggg==","orcid":"","institution":"Center for R\u0026D of Fine Chemicals of Guizhou University","correspondingAuthor":true,"prefix":"","firstName":"Wei","middleName":"","lastName":"Xue","suffix":""}],"badges":[],"createdAt":"2024-09-03 13:06:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5025191/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5025191/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66090363,"identity":"43317fb0-4b37-463e-8d28-d5d675cc0ab4","added_by":"auto","created_at":"2024-10-07 14:57:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":299306,"visible":true,"origin":"","legend":"\u003cp\u003eDesign of the target compounds.\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5025191/v1/6a206dd53b76cd6440a9be3b.png"},{"id":66090360,"identity":"a3226382-cb2d-463c-b778-5079cad255f3","added_by":"auto","created_at":"2024-10-07 14:57:02","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":190662,"visible":true,"origin":"","legend":"\u003cp\u003eobacco leaf morphology effects of \u003cstrong\u003eL20\u003c/strong\u003eand NNM against TMV \u003cem\u003ein vivo\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e(left leaf: not treated with the compound; right leaf: smeared with the compound).\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5025191/v1/fbf582a97d8bae76bc4507fc.jpeg"},{"id":66090361,"identity":"5cd41768-9052-4e2c-926b-69eee16e0586","added_by":"auto","created_at":"2024-10-07 14:57:02","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":87927,"visible":true,"origin":"","legend":"\u003cp\u003eMST results of \u003cstrong\u003eL20\u003c/strong\u003e, \u003cstrong\u003eL23\u003c/strong\u003eand NNM\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5025191/v1/e8bc9bce07c5b3ddb37a2fef.jpeg"},{"id":66090364,"identity":"97f20bd8-5c8c-46d5-be31-106826604bb6","added_by":"auto","created_at":"2024-10-07 14:57:02","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":102996,"visible":true,"origin":"","legend":"\u003cp\u003eMolecular docking results of \u003cstrong\u003eL20\u003c/strong\u003e (A-A1) and NNM (B–B1) to TMV-CP.\u003c/p\u003e","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-5025191/v1/dfd7883c459d2b81443c578e.png"},{"id":66091404,"identity":"346f2e98-6c2b-48b3-ae5e-44d3a47ea2d0","added_by":"auto","created_at":"2024-10-07 15:05:02","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":77916,"visible":true,"origin":"","legend":"\u003cp\u003eEffects of \u003cstrong\u003eL20\u003c/strong\u003e on MDA content in tobacco leaves.\u003c/p\u003e\n\u003cp\u003eVertical bars refer to mean Standard Deviation (n = 3)\u003c/p\u003e","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5025191/v1/1271e9208fcbfe121149e6fe.jpeg"},{"id":66090365,"identity":"7fe0fd1b-0bb1-4898-8181-59529d5ecb1c","added_by":"auto","created_at":"2024-10-07 14:57:02","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":71987,"visible":true,"origin":"","legend":"\u003cp\u003eEffects of \u003cstrong\u003eL20\u003c/strong\u003e on SOD activity in tobacco leaves.\u003c/p\u003e\n\u003cp\u003eVertical bars refer to mean Standard Deviation (n = 3)\u003c/p\u003e","description":"","filename":"floatimage8.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5025191/v1/7c37c68cfd605b52d5a9ab9c.jpeg"},{"id":66090366,"identity":"802ba22b-a419-4e0c-9d46-6d6c80b45064","added_by":"auto","created_at":"2024-10-07 14:57:03","extension":"jpeg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":81620,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in chlorophyll content in tobacco upon \u003cstrong\u003eL20\u003c/strong\u003ecurative treatment.\u003c/p\u003e\n\u003cp\u003eVertical bars refer to mean Standard Deviation (n = 3)\u003c/p\u003e","description":"","filename":"floatimage9.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5025191/v1/200650f661071a140a94b33b.jpeg"},{"id":69699086,"identity":"5f6c5235-3b70-4f7b-ad44-0a18b9714add","added_by":"auto","created_at":"2024-11-23 13:46:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2505291,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5025191/v1/292c25ec-4e36-4dd0-bd81-bcfb33d8ef4f.pdf"},{"id":66090362,"identity":"3a511675-3bac-470f-a414-5c3067f67ed0","added_by":"auto","created_at":"2024-10-07 14:57:02","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":41692,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 1 \u003c/strong\u003eSchematic representation of the synthesis of target compounds \u003cstrong\u003eL1-L26\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5025191/v1/2dd3913bda5d395f0da39620.png"},{"id":66090358,"identity":"4c8ecd61-8582-418b-9716-a916c6b3d1fa","added_by":"auto","created_at":"2024-10-07 14:57:02","extension":"jpeg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":108390,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraphical Abstract\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5025191/v1/68169ac6276e05a9178cd88f.jpeg"},{"id":66090367,"identity":"87746b65-bc96-4b0d-b98c-afdda46bdcbe","added_by":"auto","created_at":"2024-10-07 14:57:03","extension":"doc","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":10856497,"visible":true,"origin":"","legend":"","description":"","filename":"Supportinginformation.doc","url":"https://assets-eu.researchsquare.com/files/rs-5025191/v1/f44cd4fa5e237e16e15f8e33.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"Novel flavonoid derivatives containing benzothiazole as potential antiviral agents: design, synthesis, and biological evaluation","fulltext":[{"header":"Highlights","content":"\u003col\u003e\n \u003cli\u003eIn this paper, 26 flavonoid derivatives containing\u0026nbsp;benzothiazole\u0026nbsp;were designed and synthesized.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eL20\u0026nbsp;\u003c/strong\u003eexhibited excellent\u0026nbsp;antiviral\u0026nbsp;activity,\u0026nbsp;the EC\u003csub\u003e50\u003c/sub\u003e value of curative activities was\u0026nbsp;90.5\u0026nbsp;\u003cem\u003e\u0026mu;\u003c/em\u003eg/mL,\u0026nbsp;which was better than that of ningnanmycin (NNM: 252.0 \u0026mu;g/mL)\u003c/li\u003e\n \u003cli\u003eFurther mechanistic studies have shown that \u003cstrong\u003eL20\u0026nbsp;\u003c/strong\u003enot only has a strong binding ability with TMV-CP, but also could effectively stimulate the plant`s immune system and reduce the destructive effect of viruses on chloroplasts.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"1. Introduction","content":"\u003cp\u003ePlant virus diseases present a significant menace to global crop yields and quality annually. Plant viruses exhibit obligate parasitism within host cells; once infected with viruses, plants often remain so for their entire lifespan hence earning the moniker \u0026ldquo;plant cancer\u0026rdquo;[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Notably among them is tobacco mosaic virus (TMV), one of the most prevalent and severe global viral pathogens that spreads via sap transmission with enduring extracellular stability. Its infections significantly compromise crop quality across various cultivars such as tobacco, tomatoes, cucumbers, and peppers along with ornamental plants[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], posing substantial threats to agricultural productivity and resulting in annual global losses exceeding 100\u0026nbsp;million US dollars due to TMV[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. While conventional antiviral medications may offer some control over TMV infections, prolonged usage has led to diminished efficacy. Hence, the imperative need for developing novel, efficient, and eco-friendly antiviral agents.\u003c/p\u003e \u003cp\u003eFlavonoid is widely found in various plants and account for about one-third of the total flavonoid compounds. They have numerous vital pharmacological effects and biological activities, such as antioxidant[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], antibacterial[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], antitumor[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], antiviral[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], etc. As a natural active substance with multiple good physiological activities, widespread sources, and high safety, flavonoid is increasingly favored by researchers.\u003c/p\u003e \u003cp\u003eBenzothiazole, also known as 1,3-thiazin-2-ylidenes, is a bicyclic heterocyclic compound with a thiazole ring. Many pesticide companies have developed thiazole-based fungicides, such as benzothiostrobin and benthiavalicarb-isopropyl. Due to its excellent structural characteristics, reactivity, and coordination properties, it has a variety of biological activities, such as antibacterial[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], antiviral[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and insect-killing activities[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In addition, one of the fundamental goals of medicinal organic chemistry is to design, synthesize, and manufacture molecules that are beneficial to humans. Compounds containing thiazoles have broad potential for pharmaceutical applications, such as anti-cancer[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], anti-inflammatory[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], etc. Amides are a strong active ingredient in pesticides, and studies have shown that amides have broad-spectrum antibacterial[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], antiviral[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], herbicidal[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], and insecticidal activities[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOn this basis, a series of flavonoid derivatives containing benzothiazole were synthesized. Through biological activity screening and mechanism studies, the screened \u003cb\u003eL20\u003c/b\u003e has significantly better antiviral activity than commercially available agent NNM (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e"},{"header":"2 Results and discussion","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 \u003cem\u003eChemistry\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eThe route by which the target compounds were synthesized was shown in Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The intermediate \u003cb\u003e1\u003c/b\u003e was synthesized from different \u003cem\u003eo\u003c/em\u003e-hydroxyacetophenone and various substituted benzaldehydes. Intermediate \u003cb\u003e2\u003c/b\u003e was synthesized by intermediate \u003cb\u003e1\u003c/b\u003e via Algar-Flynn-Oyamada reaction. Intermediate \u003cb\u003e3\u003c/b\u003e was prepared by substitution reaction of 2-aminobenzothiazole and chloroacetyl chloride. Finally, intermediate \u003cb\u003e2\u003c/b\u003e and intermediate \u003cb\u003e3\u003c/b\u003e underwent a sub-stitution reaction to obtain \u003cb\u003eL1-L26\u003c/b\u003e. The structures of the compounds were characterized by NMR and HRMS spectrums and the data were offered in the \u003cb\u003eSupporting Information.\u003c/b\u003e\u003c/p\u003e \u003cp\u003eScheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Spectral characteristic of title compounds\u003c/h2\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 \u003cem\u003eAntiviral activity of L1-L26 against TMV in vivo\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eThe resistance of \u003cb\u003eL1-L26\u003c/b\u003e to TMV at a concentration of 500 \u0026micro;g/mL was tested by the half-leaf spot method using NNM as positive control. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the curative activities of \u003cb\u003eL17\u003c/b\u003e, \u003cb\u003eL20\u003c/b\u003e, and \u003cb\u003eL24\u003c/b\u003e against TMV was 67.5, 71.8, and 66.4%, respectively, which was superior to that of NNM (60.1%); and the protective activities of \u003cb\u003eL20\u003c/b\u003e and \u003cb\u003eL21\u003c/b\u003e were 64.9 and 63.9%, respectively, which were both superior to that of NNM (61.2%). The tobacco leaf morphology of \u003cb\u003eL20\u003c/b\u003e and NNM against TMV \u003cem\u003ein vivo\u003c/em\u003e were shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The EC\u003csub\u003e50\u003c/sub\u003e values of the compounds against TMV were further assayed and were shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The EC\u003csub\u003e50\u003c/sub\u003e values of curative activities of \u003cb\u003eL17\u003c/b\u003e, \u003cb\u003eL20\u003c/b\u003e, and \u003cb\u003eL24\u003c/b\u003e were 223.2, 90.5, and 146.9 \u0026micro;g/mL, respectively, which were superior to that of NNM (252.0 \u0026micro;g/mL); and the EC\u003csub\u003e50\u003c/sub\u003e values of protective activities of \u003cb\u003eL20\u003c/b\u003e and \u003cb\u003eL21\u003c/b\u003e were 202.2 and 162.6 \u0026micro;g/mL were better than that of the NNM (204.2 \u0026micro;g/mL).\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\u003eAntiviral activity of \u003cb\u003eL1-L26\u003c/b\u003e against TMV at 500 \u003cem\u003e\u0026micro;\u003c/em\u003eg/mL \u003cem\u003ein vivo\u003c/em\u003e.\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompounds\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eR\u003csub\u003e1\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCurative (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProtective (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInactivating (%)\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\u003eL1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5-Br\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e47.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e35.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e40.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5-Br\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e57.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e53.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e44.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3-OCH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5-Br\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e54.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e35.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e31.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5-Br\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e50.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e49.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e45.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-t-Bu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5-Br\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e53.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e52.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e47.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6-Cl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e46.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e53.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e31.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6-Cl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e50.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e34.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e53.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3-OCH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6-Cl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e43.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e58.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e46.5\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\u003eL9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6-Cl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e41.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e25.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e29.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-t-Bu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6-Cl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e37.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e47.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e47.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2-OCH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6-Cl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e32.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e49.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e34.1\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\u003eL12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e54.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e43.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e49.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL13\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e53.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e60.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e52.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL14\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3-OCH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e25.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e59.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e34.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e50.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e50.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e42.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL16\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-t-Bu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e55.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e56.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e45.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL17\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-Cl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e67.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e50.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e45.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL18\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e53.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e52.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e38.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL19\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e50.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e57.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e63.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL20\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3-OCH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e71.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e64.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e55.9\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\u003eL21\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e49.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e63.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e52.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL22\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-t-Bu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e52.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e59.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e51.3\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\u003eL23\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-Cl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e36.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e30.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e44.0\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\u003eL24\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6-OCH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e66.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e42.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e46.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL25\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4-CH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6-OCH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e53.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e51.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e34.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL26\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3-OCH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6-OCH\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e39.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e24.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e23.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNNM\u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e60.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e61.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e90.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e Vales are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of three replicates. \u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e The commercial antiviral agent Ningnanmycin (NNM).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eEC\u003csub\u003e50\u003c/sub\u003e values of some of the target compounds against TMV \u003cem\u003ein vivo\u003c/em\u003e.\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCompounds\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRegression equation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEC\u003csub\u003e50\u003c/sub\u003e (mg/mL)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eCurative activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eL17\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;1.2211x\u0026thinsp;+\u0026thinsp;2.1321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9807\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e223.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eL20\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;0.7249x\u0026thinsp;+\u0026thinsp;3.5816\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9693\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e90.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eL24\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;0.7120x\u0026thinsp;+\u0026thinsp;3.4571\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9814\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e146.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNNM \u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;0.7770x\u0026thinsp;+\u0026thinsp;3.1341\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9659\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e252.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eProtective activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eL20\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;0.6666x\u0026thinsp;+\u0026thinsp;3.4630\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9866\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e202.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eL21\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;0.6521x\u0026thinsp;+\u0026thinsp;3.5581\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9794\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e162.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNNM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;0.7357x\u0026thinsp;+\u0026thinsp;3.3005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9616\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e204.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e Average of three replicates. \u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e The commercial antiviral agent. Ningnanmycin (NNM)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 \u003cem\u003eStructure-activity relationship analysis\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eThe structure-activity relationship of the synthesized flavonol derivatives containing benzothiazole was evaluated. Combining the activity data in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, it is evident that the substituent group has a greater influence on the anti-TMV activity of the compounds. The compounds had better anti-TMV activity when R\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;H and R\u003csub\u003e2\u003c/sub\u003e was an electron-donating substituent. For example, curative activity: \u003cb\u003eL24\u003c/b\u003e\u0026thinsp;\u0026gt;\u0026thinsp;\u003cb\u003eL6\u003c/b\u003e (R\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;OCH\u003csub\u003e3\u003c/sub\u003e: 66.4% \u0026gt; R\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;Cl: 46.2%), \u003cb\u003eL18\u003c/b\u003e\u0026thinsp;\u0026gt;\u0026thinsp;\u003cb\u003eL1\u003c/b\u003e (R\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;CH\u003csub\u003e3\u003c/sub\u003e: 53.6% \u0026gt; R\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;Br: 47.6%). In addition, the compounds have better anti-TMV activity when R\u003csub\u003e2\u003c/sub\u003e is the same substituent and R\u003csub\u003e1\u003c/sub\u003e is an electron-donating substituent, such as when R\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;Br, the curative activity was \u003cb\u003eL2\u003c/b\u003e\u0026thinsp;\u0026gt;\u0026thinsp;\u003cb\u003eL4\u003c/b\u003e (R\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;CH\u003csub\u003e3\u003c/sub\u003e: 57.7% \u0026gt; R\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;F: 50.6%); when R\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;Cl, \u003cb\u003eL7\u003c/b\u003e\u0026thinsp;\u0026gt;\u0026thinsp;\u003cb\u003eL9\u003c/b\u003e (R\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;CH\u003csub\u003e3\u003c/sub\u003e: 50.4% \u0026gt; R\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;F: 41.2%); when R\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;CH\u003csub\u003e3\u003c/sub\u003e, \u003cb\u003eL20\u003c/b\u003e\u0026thinsp;\u0026gt;\u0026thinsp;\u003cb\u003eL21\u003c/b\u003e (R\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;CH\u003csub\u003e3\u003c/sub\u003e: 71.8% \u0026gt; R\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;F: 49.8%). From the above analysis, it can be seen that when both R\u003csub\u003e1\u003c/sub\u003e and R\u003csub\u003e2\u003c/sub\u003e are electron-donating groups, it can significantly increase the anti-TMV activity of the compounds. For example, the EC\u003csub\u003e50\u003c/sub\u003e value of the antiviral curative activity of \u003cb\u003eL20\u003c/b\u003e (R\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;3-OCH\u003csub\u003e3\u003c/sub\u003e, R\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;4-CH\u003csub\u003e3\u003c/sub\u003e) was 90.5 \u0026micro;g/mL, which was significantly lower than that of the other compounds and NNM.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 \u003cem\u003eBinding ability of L20, L23, and NNM to TMV-CP\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eTMV-CP is a key functional protein of TMV that self-assembles with viral RNA to form virus. The interactions of \u003cb\u003eL20\u003c/b\u003e, \u003cb\u003eL23\u003c/b\u003e, and NNM with TMV-CP were further analyzed by MST. The smaller the value of the dissociation constant \u003cem\u003eK\u003c/em\u003e\u003csub\u003e\u003cem\u003ed\u003c/em\u003e\u003c/sub\u003e, the stronger the binding ability of the compounds to TMV-CP. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e3\u003c/span\u003e, the \u003cem\u003eK\u003c/em\u003e\u003csub\u003e\u003cem\u003ed\u003c/em\u003e\u003c/sub\u003e values of \u003cb\u003eL20\u003c/b\u003e, \u003cb\u003eL23\u003c/b\u003e, and NNM treated with TMV-CP were 0.027\u0026thinsp;\u0026plusmn;\u0026thinsp;0.012, 0.153\u0026thinsp;\u0026plusmn;\u0026thinsp;0.036, and 0.061\u0026thinsp;\u0026plusmn;\u0026thinsp;0.030 \u0026micro;M, respectively. The results showed that the binding ability of \u003cb\u003eL20\u003c/b\u003e to TMV-CP was better than that of \u003cb\u003eL23\u003c/b\u003e and NNM, which further indicated that \u003cb\u003eL20\u003c/b\u003e had better antiviral activity, which agreed with the results of the preliminary screening for anti-TMV activity.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6 \u003cem\u003eMolecular docking of\u003c/em\u003e \u003cb\u003eL20\u003c/b\u003e \u003cem\u003eand NNM with TMV-CP\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eThe molecular docking results were shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003e, where the bioactive molecules \u003cb\u003eL20\u003c/b\u003e and NNM were embedded in the same active protein pocket of TMV and completed self-assembly with the TMV-CP subunits to form non-covalent bonding interactions. \u003cb\u003eL20\u003c/b\u003e interacted with amino acid residues (ASN-73, ARG-134, LYS-253, LYS-268, ASP-266, PRO-263) of TMV-CP through traditional hydrogen-bonding, carbon-hydrogen-bonding, pi-cation, alkyl, and pi-alkyl. Among them, amino acid residue LYS-268 formed two pi-cation bonds (2.51 \u0026Aring;, 3.08 \u0026Aring;) and one hydrogen bond (2.19 \u0026Aring;) with the aryl ring, thiazole ring, and amino group of \u003cb\u003eL20\u003c/b\u003e benzothiazole, respectively. In contrast, NNM has only one hydrogen bond with the amino acid residue LYS-268 (1.92 \u0026Aring;). In addition, the oxygen atom on the carbonyl group in \u003cb\u003eL20\u003c/b\u003e forms a carbon-hydrogen bond with amino acid residue PRO-263 (2.25 \u0026Aring;), and NNM forms a carbon-hydrogen bond with amino acid residue GLU-131 (4.30 \u0026Aring;), however, the carbon-hydrogen bond formed due to \u003cb\u003eL20\u003c/b\u003e is shorter than that of NNM. After visualization by Pymol, it is more intuitive to realize that \u003cb\u003eL20\u003c/b\u003e binds to TMV-CP more tightly and with more force than NNM.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7 \u003cem\u003eMDA content analysis\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eWhen the antioxidant mechanism in the body fails to maintain the generation and scavenging of reactive oxygen radicals in a balanced state during plant organ senescence or under adverse conditions, it leads to the peroxidation of membrane lipids of the tissues or organs, which in turn leads to the production of MDA. Therefore, the degree of membrane lipid peroxidation can be detected through MDA to indirectly valuate the degree of damage to the membrane system and plant stress tolerance. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e5\u003c/span\u003e, the content of MDA in the leaves of the CK group showed an increasing trend with time, and reached its peak on the 5th day, indicating that the plants contained antioxidant enzymes in the plant body, which had a certain regulating effect during the aging process. The content of MDA in the \u003cb\u003eL20\u003c/b\u003e group plants was lower than that in the CK group, which indicated that \u003cb\u003eL20\u003c/b\u003e was able to inhibit the adversity stress in tobacco. The content of MDA in the TMV group was significantly elevated and was the highest among the treatment groups; especially on the 7th day, it was more than twice as long as the corresponding time in the CK group, which fully reflected the serious damage of TMV to tobacco. The \u003cb\u003eL20\u003c/b\u003e\u0026thinsp;+\u0026thinsp;TMV group was significantly lower than that of the TMV group, which indicated that \u003cb\u003eL20\u003c/b\u003e could inhibit the injury of TMV to the leaves and slow down the speed of its destruction. In summary, the \u003cb\u003eL20\u003c/b\u003e can inhibit TMV infected plants and enhance the antioxidant capacity and disease resistance of plants.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.8 \u003cem\u003eEffects of L20 on SOD activity\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eSuperoxide Dismutase (SOD) plays a vital role in the biological antioxidant system, which can counteract and block the damage caused by oxygen radicals to the cells, and it also can repair the damaged cells in time to restore the damage caused by oxygen radicals to the cells. The increase in SOD activity can enhance the antiviral ability of plants. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e6\u003c/span\u003e, with the growth of time, the overall SOD activity in tobacco showed a trend of increasing and then slow decreasing. The SOD activity in the TMV group was significantly higher than that in the CK group, which was due to the fact that the plant activated the SOD system for self-protection immediately after being infected by the virus; the \u003cb\u003eL20\u003c/b\u003e group and the \u003cb\u003eL20\u003c/b\u003e\u0026thinsp;+\u0026thinsp;TMV group reached the peak value 3rd, and after that, the SOD activity showed a slow decreasing trend, but the overall activity was higher than that of the CK group and TMV group, it can be known that \u003cb\u003eL20\u003c/b\u003e can increase SOD activity in plants, enhance the ability to scavenge superoxide radicals, and improve the disease resistance of plants.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e6\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.9 \u003cem\u003eAnalysis of chlorophyll content\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eChlorophyll content is closely related to photosynthesis. The virus infests tobacco and proliferates in the host body, which will destroy the chloroplasts of the plant and interfere with the synthesis of chlorophyll, thus causing the yellowing of the leaves. As can be seen from Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e7\u003c/span\u003e, the chlorophyll content of the CK group and TMV group showed a general trend of increasing and then decreasing, reaching a peak on the 5th day, and then gradually decreasing with time as the plants senesces. On the 5th day, it was obvious that the chlorophyll content of the CK-group was higher than that of the TMV group, which was due to the fact that the chloroplasts were damaged after the TMV infection. After the 3rd day, it can be seen that the difference in chlorophyll content between the groups became more and more obvious, in which the \u003cb\u003eL20\u003c/b\u003e group was higher than the CK-group, and the \u003cb\u003eL20\u003c/b\u003e\u0026thinsp;+\u0026thinsp;TMV group was higher than the TMV group, which revealed that the \u003cb\u003eL20\u003c/b\u003e could alleviate the destructive effect of the virus on the chloroplasts, increase the content of chlorophyll indexes, and promote photosynthesis, thus increasing the resistance of tobacco to the disease\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e7\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Discussion","content":"\u003cp\u003eIn this study, 26 flavonol derivatives containing benzothiazole were synthesized. The antiviral activity experiments indicated that \u003cb\u003eL20\u003c/b\u003e possessed better inhibitory effects in terms of curative and protective activities, with EC\u003csub\u003e50\u003c/sub\u003e values of 90.5 \u0026micro;g/mL, which were better than those of NNM (252.0 \u0026micro;g/mL). It is noteworthy that the MST experiments used the TMV-CP protein as a target for the antiviral compounds, which indicated that \u003cb\u003eL20\u003c/b\u003e showed a strong affinity. Molecular docking simulation consequences revealed that \u003cb\u003eL20\u003c/b\u003e had excellent binding ability, and the results were consistent with the MST. Further experimental results showed that \u003cb\u003eL20\u003c/b\u003e could participate in the regulation of membrane lipid per-oxidation, preventing TMV infection in plants and thereby enhancing their antioxidant and defense abilities, and that \u003cb\u003eL20\u003c/b\u003e may increase the ability of the host to scavenge oxygen-free radicals \u003cem\u003ein vivo\u003c/em\u003e and induce H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e accumulation, thus improving the activities of SOD. In addition, the chlorophyll contents of tobacco plants were tested, and it was found that \u003cb\u003eL20\u003c/b\u003e could be involved in regulating the chlorophyll content of plants, promoting plant photosynthesis. Therefore, flavonol derivatives containing benzothiazole have certain antiviral activity and could be used as potential antiviral agents to control plant viruses.\u003c/p\u003e"},{"header":"4 Materials and methods","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.1 \u003cem\u003eInstruments and chemicals\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eThe melting point measurements were obtained by using the X-4B melting point instrument (Shanghai INESA Co., Ltd., Shanghai, China) without calibration. NMR spectral characterization data were obtained using a JEOL-ECX500 NMR instrument with deuterated dimethylsulfoxide as the solvent (Tokyo, Japan). High resolution mass spectra (HRMS) were gained through a Thermo Scientific Q Exactive hybrid quadrupole mass spectrometer (Thermo Scientific, USA). The Kd values of the compounds against TMV-CP were determined by using NanoTemper Monolith NT.115 micro-thermophoresis (NanoTemper, Germany). The reagents and solvents used in the experiment were purchased from Shanghai Titan Chemical Co., Ltd. (Shanghai, China) and Bositai Technology Co., Ltd. (Chongqing, China). The reagents and solvents used were of analytical grade and could be put into application without further purification.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Synthesis of compounds\u003c/h2\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e4.2.1. Preparation of intermediate\u003c/h2\u003e \u003cp\u003eIntermediates \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e were synthesized by the method reported[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], the detailed experimental methods were provided in the \u003cb\u003eSupporting Information\u003c/b\u003e. Substituted 2-aminobenzothiazole (1.00 g, 6.66 mmol) and K\u003csub\u003e2\u003c/sub\u003eCO\u003csub\u003e3\u003c/sub\u003e (1.84 g, 13.32 mmol) were dissolved in 40 mL dichloromethane, stirred at room temperature for 30 min, and slowly added chloroacetyl chloride (0.64 mL, 7.99 mmol). The reaction mixture was stirred at room temperature for 2\u0026ndash;3 h and monitored by TLC (petroleum ether: ethyl acetate\u0026thinsp;=\u0026thinsp;1:1, \u003cem\u003ev/v\u003c/em\u003e). After the reaction was completed, a large amount of white solid, intermediate \u003cb\u003e3\u003c/b\u003e (R\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;H), was obtained by suction filtration[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section3\"\u003e \u003ch2\u003e4.2.2. Synthesis of target compounds \u003cb\u003eL1-L26\u003c/b\u003e\u003c/h2\u003e \u003cp\u003eTake \u003cb\u003eL1\u003c/b\u003e as an example, intermediates \u003cb\u003e2\u003c/b\u003e (0.6 g, 2.38 mmol) and K\u003csub\u003e2\u003c/sub\u003eCO\u003csub\u003e3\u003c/sub\u003e (0.99 g, 7.14 mmol) were dissolved in 25 mL \u003cem\u003eN\u003c/em\u003e, \u003cem\u003eN\u003c/em\u003e-Dimethylformamide (DMF) and returned at 100 ℃ for 30 min, then intermediate \u003cb\u003e3\u003c/b\u003e (0.65 g, 2.85 mmol) was added at 100 ℃ for 3\u0026ndash;4 h. After the reaction completed, the product was poured into ice water, and the solid was deposited. After extraction and filtration, the crude product was separated and purified by column layer analysis (petroleum ether: ethyl acetate\u0026thinsp;=\u0026thinsp;6:1, \u003cem\u003ev/v\u003c/em\u003e) to obtain the target compound \u003cb\u003eL1\u003c/b\u003e. \u003cb\u003eL2-L26\u003c/b\u003e was obtained by reference to the above synthesis method.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(5-bromobenzo[d]thiazol-2-yl)-2-((4-oxo-2-phenyl-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL1\u003c/b\u003e). White solid, m.p. 212.2\u0026ndash;213.7 ℃; yield: 43.4%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.65 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.22 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.0 Hz, 1H, Ph-H), 8.13 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.5, 3.0 Hz, 2H, Ph-H), 8.09 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 1.5 Hz, 1H, Ph-H), 7.84\u0026ndash;7.81 (m, 1H, Ph-H), 7.76 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.66 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.55\u0026ndash;7.52 (m, 4H, Ph-H), 7.48 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11.5, 4.5 Hz, 1H, Ph-H), 4.91 (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\u003e-CO-). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 179.35 (s), 173.56 (s), 163.47 (s), 160.16 (s), 160.05 (s), 152.96 (s), 144.85 (s), 139.71 (s), 138.97 (s), 136.38 (s), 135.49 (s), 134.49 (s), 133.99 (s), 133.93 (s), 130.62 (s), 130.30 (s), 129.61 (s), 128.48 (s), 127.55 (s), 123.82 (s), 120.91 (s), 75.47 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e24\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eBrN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 508.99882, found: 508.99969.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(5-bromobenzo[d]thiazol-2-yl)-2-((4-oxo-2-(p-tolyl)-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL2\u003c/b\u003e). Purple solid, m.p. \u0026gt;230 ℃; yield: 38.6%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.70 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.07 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 1.5 Hz, 1H, Ph-H), 8.04 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 2H, Ph-H), 7.94\u0026ndash;7.91 (m, 2H, Ph-H), 7.82\u0026ndash;7.80 (m, 1H, Ph-H), 7.75 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.49\u0026ndash;7.46 (m, 1H, Ph-H), 7.43 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5, 2.0 Hz, 1H, Ph-H), 7.33 (s, 1H, Ph-H), 7.31 (s, 1H, Ph-H), 4.87 (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\u003e-CO-), 2.31 (s, 3H, Ph-CH\u003csub\u003e3\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.47 (s), 168.78 (s), 159.61 (s), 155.62 (s), 155.23 (s), 150.56 (s), 141.77 (s), 139.85 (s), 134.88 (s), 131.29 (s), 129.76 (s), 129.15 (s), 127.85 (s), 126.84 (s), 125.82 (s), 125.51 (s), 124.22 (s), 123.70 (s), 123.54 (s), 119.48 (s), 119.03 (s), 70.73 (s), 21.60 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e18\u003c/sub\u003eBrN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 521.01652, found: 521.01526.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(5-bromobenzo[d]thiazol-2-yl)-2-((2-(3-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL3\u003c/b\u003e). White solid, m.p. 183.1\u0026ndash;184.9 ℃; yield: 48.9%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.65 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.08 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 1.5 Hz, 2H, Ph-H), 7.84\u0026ndash;7.80 (m, 1H, Ph-H), 7.77 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.73\u0026ndash;7.68 (m, 3H, Ph-H), 7.48 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.46\u0026ndash;7.41 (m, 2H, Ph-H), 7.09 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 2.0 Hz, 1H, Ph-H), 4.91 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e), 3.78 (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\u003e-CO-). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e(125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.56 (s), 168.68 (s), 159.62 (s), 158.73 (s), 155.24 (s), 155.16 (s), 147.89 (s), 140.11 (s), 134.95 (s), 133.71 (s), 131.91 (s), 130.29 (s), 128.23 (s), 127.05 (s), 125.86 (s), 125.50 (s), 123.68 (s), 122.38 (s), 122.02 (s), 121.44 (s), 119.11 (s), 117.40 (s), 114.53 (s), 70.67 (s), 55.79 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e18\u003c/sub\u003eBrN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003eS: 537.01143, found: 537.01013.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(5-bromobenzo[d]thiazol-2-yl)-2-((2-(4-fluorophenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL4\u003c/b\u003e). Yellow solid, m.p. \u0026gt;230 ℃; yield: 50.1%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.68 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.22\u0026ndash;8.19 (m, 2H, Ph-H), 8.07 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 1.5 Hz, 1H, Ph-H), 7.92 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.0, 3.0 Hz, 2H, Ph-H), 7.83\u0026ndash;7.80 (m, 1H, Ph-H), 7.75 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.48 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 7.43 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5, 2.0 Hz, 1H, Ph-H), 7.38\u0026ndash;7.35 (m, 2H, Ph-H), 4.93 (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\u003e-CO-). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.44 (s), 168.79 (s), 164.93 (d, \u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 248.8 Hz), 159.59 (s), 155.18 (s), 154.41 (s), 150.53 (s), 139.80 (s), 134.93 (s), 131.99 (d, \u003csup\u003e\u003cem\u003e3\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e =8.8 Hz), 131.25 (s), 127.25 (d, \u003csup\u003e\u003cem\u003e4\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 2.5 Hz), 126.83 (s), 125.50 (s), 124.20 (s), 123.69 (s), 123.52 (s), 119.48 (s), 119.03 (s), 116.32 (d, \u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 21.3 Hz), 116.15 (s), 70.55 (s). \u003csup\u003e\u003cb\u003e19\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eF NMR\u003c/b\u003e (470 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e -108.47. \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e24\u003c/sub\u003eH\u003csub\u003e15\u003c/sub\u003eBrFN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 524.99144, found: 524.99030.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(5-bromobenzo[d]thiazol-2-yl)-2-((2-(4-(tert-butyl)phenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL5\u003c/b\u003e). White solid, m.p. 219.1\u0026ndash;220.9 ℃; yield: 44.6%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.71 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH-\u003c/span\u003e), 8.07 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;13.5, 5.0 Hz, 3H, Ph-H), 7.92 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 2H, Ph-H), 7.83\u0026ndash;7.79 (m, 1H, Ph-H), 7.74 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.52\u0026ndash;7.46 (m, 3H, Ph-H), 7.43 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5, 2.0 Hz, 1H, Ph-H), 4.88 (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\u003e-CO-), 1.23 (s, 9H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eC(CH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e)\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.44 (s), 168.72 (s), 159.58 (s), 155.61 (s), 155.23 (s), 154.49 (s), 150.54 (s), 139.83 (s), 134.88 (s), 131.27 (s), 129.02 (s), 127.90 (s), 126.82 (s), 125.97(s), 125.82(s), 125.51 (s), 124.19 (s), 123.71 (s), 123.54 (s), 119.46 (s), 119.00 (s), 70.74 (s), 35.19 (s), 31.32 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e28\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003eBrN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 563.06347, found: 563.06207.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN\u003c/em\u003e-\u003cem\u003e(6-chlorobenzo[d]thiazol-2-yl)-2-((4-oxo-2-phenyl-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL6\u003c/b\u003e). Purple solid, m.p. 182.9\u0026ndash;183.4 ℃; yield: 51.0%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.66 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.13 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.5, 3.0 Hz, 2H, Ph-H), 8.10\u0026ndash;8.08 (m, 2H, Ph-H), 7.84\u0026ndash;7.81 (m, 1H, Ph-H), 7.76 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.72 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.55\u0026ndash;7.53 (m, 3H, Ph-H), 7.49 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.42 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5, 2.0 Hz, 1H, Ph-H), 4.91 (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\u003e-CO-). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.59 (s), 168.79 (s), 158.73 (s), 155.40 (s), 155.28 (s), 147.90 (s), 140.07 (s), 134.96 (s), 133.71 (s), 131.63 (s), 130.72 (s), 129.23 (s), 129.17 (s), 128.24 (s), 127.06 (s), 125.87 (s), 125.53 (s), 123.70 (s), 122.39 (s), 122.02 (s), 119.06 (s), 70.69 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e24\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 463.05138, found: 463.05002.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(6-chlorobenzo[d]thiazol-2-yl)-2-((4-oxo-2-(p-tolyl)-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL7\u003c/b\u003e). White solid, m.p. 227.8-228.5 ℃; yield: 44.6%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.65 (s 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.08 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 2H, Ph-H), 8.04 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 2H, Ph-H), 7.83\u0026ndash;7.80 (m, 1H, Ph-H), 7.76 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.72 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.48 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.43 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.33 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 2H, Ph-H), 4.87 (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\u003e-CO-), 2.32 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.51 (s), 168.76 (s), 158.75 (s), 155.68 (s), 155.24 (s), 147.92 (s), 141.78 (s), 139.88 (s), 134.89 (s), 133.73 (s), 129.77 (s), 129.15 (s), 128.23 (s), 127.85 (s), 127.05 (s), 125.82 (s), 125.52 (s), 123.70 (s), 122.39 (s), 122.01 (s), 119.02 (s), 70.79 (s), 21.60 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e18\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 477.06703, found: 477.06662.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(6-chlorobenzo[d]thiazol-2-yl)-2-((2-(3-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL8\u003c/b\u003e). Purple solid, m.p. 205.8-207.4 ℃; yield: 39.4%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.65 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.09\u0026ndash;8.07 (m, 2H, Ph-H), 7.84\u0026ndash;7.80 (m, 1H, Ph-H), 7.77 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.72 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.69\u0026ndash;7.68 (m, 2H, Ph-H), 7.48 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 7.44\u0026ndash;7.41 (m, 2H, Ph-H), 7.09 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 2.0 Hz, 1H, Ph-H), 4.91 (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\u003e-CO-), 3.78 (s, 3H, Ph-OCH\u003csub\u003e3\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.08 (s), 168.32 (s), 159.14 (s), 158.45 (s), 154.76 (s), 154.66 (s), 147.44 (s), 139.64 (s), 134.47 (s), 133.25 (s), 131.45 (s), 129.81 (s), 127.67 (s), 126.53 (s), 125.39 (s), 125.02 (s), 123.21 (s), 121.85 (s), 121.52 (s), 120.96 (s), 118.64 (s), 116.93 (s), 114.04 (s), 70.23 (s), 55.31 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e18\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003eS: 493.06195, found: 493.06088.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(6-chlorobenzo[d]thiazol-2-yl)-2-((2-(4-fluorophenyl)-4-oxo-4H-chromen-3-yl)oxy) acetamide\u003c/em\u003e (\u003cb\u003eL9\u003c/b\u003e). White solid, m.p. \u0026gt;230 ℃; yield: 41.9%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.59 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.16 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5, 6.0 Hz, 1H, Ph-H), 8.02 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.0 Hz, 2H, Ph-H), 8.01\u0026ndash;7.93 (m, 1H, Ph-H), 7.79\u0026ndash;7.75 (m, 1H, Ph-H), 7.71 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;16.0, 8.5 Hz, 1H, Ph-H), 7.66 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.43 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.40\u0026ndash;7.27 (m, 3H, Ph-H), 4.95\u0026ndash;4.89 (m, 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\u003e-CO-). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e, 174.04 (s), 168.28 (s), 164.47 (d, \u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 248.6 Hz), 158.24 (s), 54.71 (s), 153.98 (s), 147.41 (s), 139.35 (s), 134.46 (s), 133.22 (s), 131.51(d, \u003csup\u003e\u003cem\u003e3\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 8.8 Hz), 127.77 (s), 126.57 (s), 125.39 (s), 125.03 (s), 124.87 (s), 123.21 (s), 121.52 (s), 118.55 (s), 115.86 (d, \u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 21.6 Hz), 70.11 (s). \u003csup\u003e\u003cb\u003e19\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eF NMR\u003c/b\u003e (476 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e -108.46. \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e24\u003c/sub\u003eH\u003csub\u003e15\u003c/sub\u003eClFN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS:481.04196, found: 481.04123.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((2-(4-(tert-butyl)phenyl)-4-oxo-4H-chromen-3-yl)oxy)-N-(6-chlorobenzo[d]thiazol-2-yl)acetamide\u003c/em\u003e (\u003cb\u003eL10\u003c/b\u003e). White solid, m.p. 171.5\u0026ndash;172.4 ℃; yield: 39.5%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.66 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.09\u0026ndash;8.06 (m, 3H, Ph-H), 8.05\u0026ndash;8.04 (m, 1H, Ph-H), 7.81\u0026ndash;7.79 (m, 1H, Ph-H), 7.74 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.71 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.53\u0026ndash;7.50 (m, 2H, Ph-H), 7.49\u0026ndash;7.46 (m, 1H, Ph-H), 7.43\u0026ndash;7.41 (m, 1H, Ph-H), 4.88 (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\u003e-CO-), 1.23 (s, 9H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eC(CH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e)\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.47 (s), 168.70 (s), 158.71 (s), 155.65 (s), 155.24 (s), 154.51 (s), 147.88 (s), 139.86 (s), 134.89 (s), 133.70 (s), 129.96 (s), 129.01 (s), 128.23 (s), 127.88 (s), 127.04 (s), 125.98 (s), 125.51 (s), 123.70 (s), 122.38 (s), 121.99 (s), 119.00 (s), 70.78 (s), 35.19 (s), 31.31 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e28\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 519.11398, found: 519.11267.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(6-chlorobenzo[d]thiazol-2-yl)-2-((2-(2-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e \u003cb\u003e(L11).\u003c/b\u003e Yellow solid, m.p. \u0026gt;230 ℃; yield: 43.8%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.43 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.10\u0026ndash;8.03 (m, 2H, Ph-H), 7.76 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 7.67 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.62 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.53\u0026ndash;7.50 (m, 1H, Ph-H), 7.47\u0026ndash;7.44 (m, 2H, Ph-H), 7.38 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5, 2.0 Hz, 1H, Ph-H), 7.10 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.01 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 4.73 (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\u003e-CO-), 3.71 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 173.71 (s), 168.21 (s), 158.25 (s), 156.88 (s), 155.53 (s), 155.23 (s), 147.42 (s), 140.22 (s), 134.41 (s), 133.23 (s), 132.46 (s), 130.61 (s), 127.73 (s), 126.57 (s), 125.40 (s), 125.12 (s), 123.51 (s), 121.89 (s), 121.54 (s), 120.33 (s), 119.16 (s), 118.57 (s), 111.79 (s), 70.46 (s), 55.74 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e18\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003eS: 493.06195, found: 493.06256.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(benzo[d]thiazol-2-yl)-2-((4-oxo-2-phenyl-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL12\u003c/b\u003e). Yellow solid, m.p. 201.9\u0026ndash;203.8 ℃; yield: 46.2%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.57 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.09 (m, 3H, Ph-H), 7.94 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.83\u0026ndash;7.80 (m, 1H, Ph-H), 7.74 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;13.5, 8.0 Hz, 2H, Ph-H), 7.55\u0026ndash;7.53 (m, 3H, Ph-H), 7.48 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.40 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H, 7.27 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 4.99 (m, 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\u003e-CO-). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.63 (s), 168.59 (s), 165.96 (s), 157.86 (s), 155.43 (s), 155.28 (s), 140.10 (s), 134.96 (s), 131.64 (s), 130.72 (s), 130.02 (s), 129.42 (s), 129.22 (s), 126.73 (s), 125.87 (s), 125.54 (s), 124.22 (s), 123.70 (s), 122.30 (s), 121.17 (s), 119.06 (s), 70.74 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e24\u003c/sub\u003eH\u003csub\u003e17\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 429.09035, found: 429.08932.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(benzo[d]thiazol-2-yl)-2-((4-oxo-2-(p-tolyl)-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL13\u003c/b\u003e). White solid, m.p. \u0026gt;230 ℃; yield: 33.4%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.57 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.09 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 8.06 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 2H, Ph-H), 7.95 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.82 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.75 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;16.5, 8.0 Hz, 2H, Ph-H), 7.49 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.41 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.34 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 2H, Ph-H), 7.28 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 4.87 (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\u003e-CO-), 2.33 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.53 (s), 168.54 (s), 157.85 (s), 155.66 (s), 155.25 (s), 149.02 (s), 141.79 (s), 139.91 (s), 134.89 (s), 132.02 (s), 129.79 (s), 129.15 (s), 127.87 (s), 126.71 (s), 125.83 (s), 125.52 (s), 124.21 (s), 123.71 (s), 122.30 (s), 121.19 (s), 119.04 (s), 70.80 (s), 21.61 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e19\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 443.10600, found: 443.10461.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(benzo[d]thiazol-2-yl)-2-((2-(3-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL14\u003c/b\u003e). White solid, m.p. 191.5\u0026ndash;192.0 ℃; yield: 35.6%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.52 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.07 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.5 Hz, 1H, Ph-H), 7.92 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 7.80\u0026ndash;7.74 (m, 2H, Ph-H), 7.68 (s, 3H, Ph-H), 7.51\u0026ndash;7.36 (m, 3H, Ph-H), 7.25 (s, 1H, Ph-H), 7.07 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.5 Hz, 1H, Ph-H), 4.89 (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\u003e-CO-), 3.76 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO) \u003cem\u003eδ\u003c/em\u003e 174.53 (s), 168.42 (s), 159.59 (s), 157.79 (s), 155.20 (s), 155.11 (s), 148.94 (s), 140.09 (s), 134.88 (s), 131.96 (s), 131.88 (s), 130.25 (s), 126.65 (s), 125.81 (s), 125.45 (s), 124.15 (s), 123.64 (s), 122.25 (s), 121.38 (s), 121.12 (s), 119.06 (s), 117.37 (s), 114.47 (s), 70.65 (s), 55.74 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e19\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003eS: 459.10092, found: 459.10016.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(benzo[d]thiazol-2-yl)-2-((2-(4-fluorophenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL15\u003c/b\u003e). White solid, m.p. 196.7\u0026ndash;198.8 ℃; yield: 36.5%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.52 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.22\u0026ndash;8.18 (m, 2H, Ph-H), 8.06 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 1.5 Hz, 1H, Ph-H), 7.91 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.79\u0026ndash;7.77 (m, 1H, Ph-H), 7.74\u0026ndash;7.72 (m, 1H, Ph-H), 7.70 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.47\u0026ndash;7.44 (m, 1H, Ph-H), 7.41\u0026ndash;7.36 (m, 2H, Ph-H), 7.35\u0026ndash;7.33 (m, 1H, Ph-H), 7.27\u0026ndash;7.23 (m, 1H, Ph-H), 4.91 (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\u003e-CO-). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.50 (s), 168.54 (s), 164.95 (d, \u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 248.8 Hz), 157.84 (s), 155.21 (s), 154.46 (s), 149.01 (s), 139.87 (s), 134.94 (s), 132.00 (d, \u003csup\u003e\u003cem\u003e3\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 8.8 Hz), 127.27 (d, \u003csup\u003e4\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 2.5 Hz), 126.71 (s), 125.87 (s), 125.52 (s), 124.20 (s), 123.71 (s), 122.29 (s), 121.18 (s), 119.05 (s), 116.35(d, \u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 21.3 Hz), 70.61 (s). \u003csup\u003e\u003cb\u003e19\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eF NMR\u003c/b\u003e (470 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e -108.45. \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e24\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eFN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 447.08093, found: 447.07941.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(benzo[d]thiazol-2-yl)-2-((2-(4-(tert-butyl)phenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL16\u003c/b\u003e). Yellow solid, m.p. 182.9\u0026ndash;184.4 ℃; yield: 32.2%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.92 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.13\u0026ndash;8.11 (m, 2H, Ph-H), 7.99 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 1.5 Hz, 1H, Ph-H), 7.90 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 2H, Ph-H), 7.67 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 2H, Ph-H), 7.48\u0026ndash;7.46 (m, 2H, Ph-H), 7.41\u0026ndash;7.34 (m, 2H, Ph-H), 7.34 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11.5, 4.0 Hz, 1H, Ph-H), 4.98 (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\u003e-CO-), 1.21 (s, 9H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eC(CH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e)\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 178.18 (s), 174.24 (s), 167.32 (s), 155.05 (s), 154.72 (s), 154.18 (s), 139.49 (s), 137.11 (s), 134.50 (s), 128.95 (s), 128.30 (s), 126.78 (s), 125.84 (s), 125.43 (s), 124.77 (s), 124.32 (s), 123.82 (s), 122.31 (s), 118.86 (s), 113.17 (s), 72.46 (s), 35.13 (s), 31.31 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e28\u003c/sub\u003eH\u003csub\u003e25\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 485.15295, found: 485.15186.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(benzo[d]thiazol-2-yl)-2-((2-(4-chlorophenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL17\u003c/b\u003e). Yellow solid, m.p. 210.9\u0026ndash;212.1 ℃; yield: 37.9%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.53 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.17 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 2H, Ph-H), 8.08 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 1.5 Hz, 1H, Ph-H), 7.94 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.84\u0026ndash;7.80 (m, 1H, Ph-H), 7.75 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.72 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.60 (s, 1H, Ph-H), 7.58 (s, 1H, Ph-H), 7.50\u0026ndash;7.46 (m, 1H, Ph-H), 7.40 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11.0, 4.0 H, 1H, Ph-Hz), 7.29\u0026ndash;7.26 (m, 1H, Ph-H), 4.94 (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\u003e-CO-). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.47 (s), 168.49 (s), 157.83 (s), 155.20 (s), 154.13 (s), 149.00 (s), 140.15 (s), 136.33 (s), 134.99 (s), 132.01(s), 131.07 (s), 129.60 (s), 129.23 (s), 126.70 (s), 125.89 (s), 125.52 (s), 124.20 (s), 123.72 (s), 122.29 (s), 121.17 (s), 119.05 (s), 70.61 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e24\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 463.05138, found: 463.05011.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(4-methylbenzo[d]thiazol-2-yl)-2-((4-oxo-2-phenyl-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL18\u003c/b\u003e). Yellow solid, m.p. 184.2\u0026ndash;185.4 ℃; yield: 39.5%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.56 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.16\u0026ndash;8.13 (m, 2H, Ph-H), 8.08 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 1.5 Hz, 1H, Ph-H), 7.83\u0026ndash;7.80 (m, 1H, Ph-H), 7.77\u0026ndash;7.74 (m, 2H, Ph-H), 7.53 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.5, 2.0 Hz, 3H, Ph-H), 7.48 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11.5, 4.5 Hz, 1H, Ph-H), 7.22 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 7.17 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 4.93 (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\u003e-CO-), 2.53 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 173.96 (s), 167.89 (s), 156.49 (s), 154.78(s), 154.74(s), 147.60 (s), 139.48 (s), 134.42 (s), 131.10 (s), 130.32 (s), 129.98 (s), 129.54 (s), 128.76 (s), 128.67 (s), 126.71 (s), 125.35 (s), 125.04 (s), 123.67 (s), 123.28 (s), 119.19 (s), 118.58 (s), 69.90 (s), 18.01 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e19\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 443.10600, found: 443.10471.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(4-methylbenzo[d]thiazol-2-yl)-2-((4-oxo-2-(p-tolyl)-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL19\u003c/b\u003e). Yellow solid, m.p. 158.8\u0026ndash;160.3 ℃; yield: 44.3%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 8.08\u0026ndash;8.04 (m, 3H, Ph-H), 7.78 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.73 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.65 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.45 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.30 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 2H, Ph-H), 7.14 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 7.08 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 4.82 (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\u003e-CO-), 2.48 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e), 2.29 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.39 (s), 155.18 (s), 148.44 (s), 141.59 (s), 134.74 (s), 131.89 (s), 129.72 (s), 129.16 (s), 128.04 (s), 126.79 (s), 125.71 (s), 125.49 (s), 123.79 (s), 119.43 (s), 118.99 (s), 70.99 (s), 21.57 (s), 18.54 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e26\u003c/sub\u003eH\u003csub\u003e21\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 457.12165, found: 457.12039.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((2-(3-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)-N-(4-methylbenzo[d]thiazol-2-yl)acetamide\u003c/em\u003e (\u003cb\u003eL20\u003c/b\u003e). White solid, m.p. 165.5-166.9 ℃; yield: 41.0%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.54 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.07 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.81 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.76\u0026ndash;7.72 (m, 2H, Ph-H), 7.69 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 2H, Ph-H), 7.46 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.43 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.21 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 7.16 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 7.07 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 4.91 (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\u003e-CO-), 3.77 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOCH\u003c/span\u003e\u003csub\u003e3\u003c/sub\u003e), 2.52 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.44 (s), 168.26 (s), 159.60 (s), 156.93 (s), 155.21 (s), 155.04 (s), 148.03 (s), 139.99 (s), 134.89 (s), 131.95 (s), 131.64 (s), 130.46 (s), 130.27 (s), 127.18 (s), 125.82 (s), 125.47 (s), 124.17 (s), 123.71 (s), 121.42 (s), 119.64 (s), 119.07 (s), 117.36 (s), 114.51 (s), 70.40 (s), 55.76 (s), 18.46 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e26\u003c/sub\u003eH\u003csub\u003e21\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003eS: 473.11657, found: 473.11505.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((2-(4-fluorophenyl)-4-oxo-4H-chromen-3-yl)oxy)-N-(4-methylbenzo[d]thiazol-2-yl)acetamide\u003c/em\u003e (\u003cb\u003eL21\u003c/b\u003e). White solid, m.p. 200.4\u0026ndash;201.8 ℃; yield: 51.2%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.55 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.23 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5, 5.5 Hz, 2H, Ph-H), 8.07 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.81 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.76\u0026ndash;7.72 (m, 2H, Ph-H), 7.47 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.36 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 2H, Ph-H), 7.21 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 7.16 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 4.95 (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\u003e-CO-), 2.53 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.32 (s), 168.34 (s), 164.91(d, \u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 248.8 Hz), 156.95 (s), 155.17 (s), 154.28 (s), 148.07 (s), 139.72 (s), 134.87 (s), 131.99(d, 3\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026thinsp;\u0026minus;\u0026thinsp;F\u003c/em\u003e\u003c/sub\u003e = 8.8 Hz), 131.65 (s), 130.45 (s), 127.17 (s), 125.82 (s), 125.49 (s), 124.13 (s), 123.75 (s), 119.65 (s), 119.03 (s), 116.29(d, \u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eJ\u003c/em\u003e\u003csub\u003e\u003cem\u003eC\u0026minus;F\u003c/em\u003e\u003c/sub\u003e = 21.3 Hz), 116.12 (s), 70.30 (s), 18.48 (s).\u003csup\u003e\u003cb\u003e19\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eF NMR\u003c/b\u003e (470 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e -108.58. \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e18\u003c/sub\u003eFN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 461.09658, found: 461.09515.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((2-(4-(tert-butyl)phenyl)-4-oxo-4H-chromen-3-yl)oxy)-N-(4-methylbenzo[d]thiazol-2-yl)acetamide\u003c/em\u003e (\u003cb\u003eL22\u003c/b\u003e). Yellow solid, m.p. 180.0-181.6 ℃; yield: 45.9%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.57 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.07\u0026ndash;8.04 (m, 3H, Ph-H), 7.80\u0026ndash;7.76 (m, 1H, Ph-H), 7.71 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5, 4.5 Hz, 2H, Ph-H), 7.50\u0026ndash;7.47 (m, 2H, Ph-H), 7.45 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11.0, 4.0 Hz, 1H, Ph-H), 7.19 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 7.16\u0026ndash;7.13 (m, 1H, Ph-H), 4.89 (s, 2H, 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\u003e-CO-), 2.52 (s, 3H, Ph-CH\u003csub\u003e3\u003c/sub\u003e), 1.20 (s, 9H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eC(CH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3)3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.30 (s), 168.23 (s), 156.93 (s), 155.46 (s), 155.18 (s), 154.41 (s), 148.06 (s), 139.71 (s), 134.77 (s), 131.66 (s), 130.43 (s), 129.95 (s), 128.99 (s), 127.93 (s), 127.14 (s), 125.90 (s), 125.47 (s), 124.12 (s), 123.74 (s), 119.60 (s), 118.94 (s), 70.47 (s), 35.13 (s), 31.27 (s), 18.48 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e27\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 499.16860, found: 499.16733.\u003c/p\u003e \u003cp\u003e \u003cem\u003e2-((2-(4-chlorophenyl)-4-oxo-4H-chromen-3-yl)oxy)-N-(4-methylbenzo[d]thiazol-2-yl)acetamide\u003c/em\u003e (\u003cb\u003eL23\u003c/b\u003e). Yellow solid, m.p. 201.9\u0026ndash;203.6 ℃; yield: 52.8%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.53 (s, 1H,-CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.17 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 2H, Ph-H), 8.07 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.82 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.76\u0026ndash;7.72 (m, 2H, Ph-H), 7.58 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 2H, Ph-H), 7.48 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 7.21 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 7.16 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.5 Hz, 1H, Ph-H), 4.94 (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\u003e-CO-), 2.52 (s, 3H, Ph-CH\u003csub\u003e3\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.33 (s), 168.31 (s), 156.95 (s), 155.18 (s), 154.04 (s), 148.05 (s), 140.01 (s), 136.27 (s), 134.97 (s), 131.63 (s), 131.09 (s), 130.45 (s), 129.64 (s), 129.19 (s), 127.18 (s), 125.88 (s), 125.51 (s), 124.16 (s), 123.76 (s), 119.65 (s), 119.05 (s), 70.34 (s), 18.48 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e18\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS: 477.06703, found: 477.06583.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(6-methoxybenzo[d]thiazol-2-yl)-2-((4-oxo-2-phenyl-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e \u003cb\u003e(L24)\u003c/b\u003e. Yellow solid, m.p. 149.1\u0026ndash;150.9 ℃; yield: 48.5%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.44 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.13 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.5, 3.0 Hz, 2H, Ph-H), 8.09 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0, 1.5 Hz, 1H, Ph-H), 7.82\u0026ndash;7.81 (m, 1H, Ph-H), 7.76 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 1H, Ph-H), 7.62 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9.0 Hz, 1H, Ph-H), 7.55\u0026ndash;7.52 (m, 4H, Ph-H), 7.49 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11.0, 4.0 Hz, 1H, Ph-H), 6.99 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9.0, 2.5 Hz, 1H, Ph-H), 4.88 (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\u003e-CO-), 3.76 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.64(s), 168.26(s), 156.72(s), 155.74(s), 155.43(s), 155.39(s), 143.08(s), 140.13(s), 134.95(s), 133.33(s), 131.64(s), 130.72(s), 129.22(s), 125.87(s), 125.54(s), 123.70(s), 121.80(s), 119.06(s), 115.52(s), 105.22(s), 70.72(s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e19\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003eS: 459.10092, found: 459.09961.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(6-methoxybenzo[d]thiazol-2-yl)-2-((4-oxo-2-(p-tolyl)-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e (\u003cb\u003eL25\u003c/b\u003e). Yellow solid, m.p. 172.4\u0026ndash;174.3 ℃; yield: 36.5%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.44 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.08 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.0 Hz, 1H, Ph-H), 8.04 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 2H, Ph-H), 7.83\u0026ndash;7.79 (m, 1H, Ph-H), 7.75 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.62 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9.0 Hz, 1H, Ph-H), 7.54\u0026ndash;7.46 (m, 2H, Ph-H), 7.33 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.0 Hz, 2H, Ph-H), 6.99 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5, 2.5 Hz, 1H, Ph-H), 4.83 (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\u003e-CO-), 3.76 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e), 2.32 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.56 (s), 168.22 (s), 156.73 (s), 155.70 (s), 155.24 (s), 141.80 (s), 139.93 (s), 134.89 (s), 129.80 (s), 129.13 (s), 127.85 (s), 125.82 (s), 125.52 (s), 121.81 (s), 119.03 (s), 115.52 (s), 105.23 (s), 70.80 (s), 56.14 (s), 21.61 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e26\u003c/sub\u003eH\u003csub\u003e21\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003eS: 473.11657, found: 473.11581.\u003c/p\u003e \u003cp\u003e \u003cem\u003eN-(6-methoxybenzo[d]thiazol-2-yl)-2-((2-(3-methoxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)acetamide\u003c/em\u003e \u003cb\u003e(L26)\u003c/b\u003e. White solid, m.p. 160.3\u0026ndash;161.5 ℃; yield: 36.4%. \u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eH NMR\u003c/b\u003e (500 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 12.42 (s, 1H, -CO-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNH\u003c/span\u003e-), 8.11\u0026ndash;8.06 (m, 1H, Ph-H ), 7.82 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11.0, 4.0 Hz, 1H, Ph-H), 7.76 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5 Hz, 1H, Ph-H), 7.69 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.0 Hz, 1H, Ph-H), 7.68 (s, 1H, Ph-H), 7.62 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9.0 Hz, 1H, Ph-H), 7.53 (d, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.0 Hz, 1H, Ph-H), 7.48 (t, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.0 Hz, 1H, Ph-H), 7.45 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;13.5, 5.5 Hz, 1H, Ph-H), 7.12\u0026ndash;7.07 (m, 1H, Ph-H), 6.99 (dd, \u003cem\u003eJ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8.5, 2.5 Hz, 1H, Ph-H), 4.88 (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\u003e-CO-), 3.79 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e), 3.76 (s, 3H, Ph-\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOCH\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e3\u003c/span\u003e\u003c/sub\u003e). \u003csup\u003e\u003cb\u003e13\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eC NMR\u003c/b\u003e (125 MHz, DMSO-\u003cem\u003ed\u003c/em\u003e) \u003cem\u003eδ\u003c/em\u003e 174.61 (s), 168.15 (s), 159.65 (s), 156.72 (s), 155.74 (s), 155.25 (s), 155.18 (s), 143.09 (s), 140.17 (s), 134.93 (s), 133.34 (s), 131.92 (s), 130.31 (s), 125.86 (s), 125.51 (s), 123.68 (s), 121.79 (s), 121.42 (s), 119.10 (s), 117.44 (s), 115.51 (s), 114.50 (s), 105.23 (s), 70.69 (s), 56.13 (s), 55.80 (s). \u003cb\u003eHRMS (ESI)\u003c/b\u003e m/z [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calcd for C\u003csub\u003e26\u003c/sub\u003eH\u003csub\u003e21\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003eS: 489.11148, found: 489.11078.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e4.3 \u003cem\u003eIn vivo antiviral activity\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eAccording to literature reports[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], \u003cb\u003eL1-L26\u003c/b\u003e were selected as the experimental objects for \u003cem\u003ein vivo\u003c/em\u003e anti-virus testing using the semi-leaf blight method, with dimethyl sulfoxide (DMSO) solution as the negative control and commercial NNM as the positive control. The tobaccos treated were cultivated in an artificial climate chamber (28 ℃) for 2\u0026ndash;3 d. When spots appear on the leaves, the number of spots on both sides is counted and the inhibition rate is calculated. Each drug was repeated three times. Specific experimental methods were described in the \u003cb\u003eSupporting Information\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e4.4 \u003cem\u003eMicroscale thermophoresis experiment\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eThe modes of binding of the target compounds to tobacco mosaic virus capsid proteins (TMV-CP) and the affinity of intermolecular interactions were investigated using MST assays. The binding affinity of \u003cb\u003eL20\u003c/b\u003e and \u003cb\u003eL23\u003c/b\u003e to TMV-CP were tested with reference to the methodology reported in the literature[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], and the commercial drug NNM was used as a positive control. The details of the experimental methods were described in the \u003cb\u003eSupporting Information\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e4.5 \u003cem\u003eMolecular docking experiment\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eTMV-CP not only has the function of protecting nucleic acid from degradation, but also has the function of assisting TMV long-distance transport, determining the host range and participating in nucleic acid replication. TMV-CP is often used as a potential target in the study of antiviral agents. Utilizing molecular docking simulations for predicting interactions between ligand compounds and receptor proteins to validate their binding affinity. Following established methodology detailed in literature reports[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e], molecular docking simulations involving \u003cb\u003eL20\u003c/b\u003e and NNM with TMV-CP were conducted utilizing. Specific experimental methodologies were outlined within \u003cb\u003eSupporting Information\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003e4.6 \u003cem\u003eMDA content test\u003c/em\u003e\u003c/h2\u003e \u003cp\u003ePrevious studies have reported that the content of MDA can reflect the degree of membrane damages in tobacco leaves infected by TMV[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. The healthy, uniformly sized tobacco leaves were selected as the experimental subjects. The experiment was set up with four different treatments (\u003cb\u003eCK\u003c/b\u003e, \u003cb\u003eL20\u003c/b\u003e, \u003cb\u003eTMV\u003c/b\u003e, and \u003cb\u003eTMV\u0026thinsp;+\u0026thinsp;L20)\u003c/b\u003e, the whole leaves were induced with 500 \u0026micro;g/mL \u003cb\u003eL20\u003c/b\u003e, and 0.5% DMSO to obtain the groups \u003cb\u003eCK\u003c/b\u003e and \u003cb\u003eL20\u003c/b\u003e; the entire leaf was infected with 500-fold diluted virus liquid to obtain \u003cb\u003eTMV\u003c/b\u003e group; the entire leaf was treated with 500 \u0026micro;g/mL \u003cb\u003eL20\u003c/b\u003e first, and then infected with 500-fold diluted virus liquid after 24 h to obtain \u003cb\u003eTMV\u0026thinsp;+\u0026thinsp;L20\u003c/b\u003e. Each treatment had 4 tobacco plants. Samples were collected at intervals of 1, 3, 5 and 7 d. The MDA content was determined by liquid nitrogen grinding and following the instructions in the assay kit.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003e4.7 \u003cem\u003eSOD activity measurement\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eAccording to literature reports[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], the SOD activity was determined in the leaves after the \u003cb\u003eL20\u003c/b\u003e treatment, with the same four treatments as the MDA content determination experiment, 0.1 g of leaf tissue was weighed after the leaf veins were removed, and the SOD activity was determined following the instructions in the assay kit.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section2\"\u003e \u003ch2\u003e4.8 \u003cem\u003eIn vivo chlorophyll content test\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eChlorophyll is one of the most important pigments related to photosynthesis, and its content is closely related to the health of the plant. According to the reported method[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], the change in chlorophyll content in the leaves after the \u003cb\u003eL20\u003c/b\u003e treatment was determined, with the same treatment and sampling steps as the MDA content determination experiment. When cells die, chlorophyll was released from the chloroplasts. Free chlorophyll is highly unstable and can be broken down by light, acid, alkali, oxygen, oxidants, etc. Therefore, leaf green content should be determined immediately after leaf sampling. Specific experimental methodologies were outlined within \u003cb\u003eSupporting Information\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge\u0026nbsp;the\u0026nbsp;Key Research and Development Program of Hainan Province\u0026nbsp;(No. ZDYF2024XDNY202),\u0026nbsp;the Science Foundation of Guizhou Province\u0026nbsp;(No. ZK2024008), Chinese Academy of Tropical Agricultural Sciences for Science and Technology Innovation Team of National Tropical Agricultural Science Center (No. CATASCXTD202410).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe appendix: Supplementary material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe \u003cstrong\u003eSupporting Information\u003c/strong\u003e includes the characterization data of the target compound, NMR and HRMS spectra, and the detailed operation steps of studying the target compound matrix.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe current study is an outcome of constructive discussion with W.X; J.T and C.M.H performed synthesis and characterization experiments on the target compounds; J.T and Y.H.W completed experiments on preliminary screening and mechanism of action studies of antiviral activity; J.T, X.P.L and J.Y.L carried out the NMR and HRMS spectral analyses; J.T and H.T.P prepared figures 1-7 and table 1-3; T.J, X.W, and D.L 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\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no competing financial interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHao YA, Guo JC, Wang ZW, Liu YX, Li YQ, Ma DJ, Wang QM (2020) Discovery of tryptanthrins as novel antiviral and anti-phytopathogenic-fungus agents. 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J Saudi Chem Soc 27(6):101751. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jscs.2023.101751\u003c/span\u003e\u003cspan address=\"10.1016/j.jscs.2023.101751\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eList of Graphical abstract, Scheme1 and Figure Titles\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Scheme","content":"\u003cp\u003eScheme 1 is available in the Supplementary Files section.\u003c/p\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":"flavonoid, benzothiazole, antiviral activity, mechanism of action","lastPublishedDoi":"10.21203/rs.3.rs-5025191/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5025191/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA series of flavonol derivatives containing benzothiazole were designed and synthesized. The structures of all the compounds were characterized by NMR and HRMS. The results of the bioactivity assay showed that some of the target compounds possessed outstanding \u003cem\u003ein vivo\u003c/em\u003e antiviral activity against the tobacco mosaic virus (TMV). Among them, the median effective concentration (EC\u003csub\u003e50\u003c/sub\u003e) of \u003cb\u003eL20\u003c/b\u003e was 90.5 \u0026micro;g/mL for curative activities against TMV, which was better than that of ningnanmycin (NNM: 252.0 \u0026micro;g/mL). The microcalorimetric thermophoresis (MST) and molecular docking experiments showed that \u003cb\u003eL20\u003c/b\u003e had a strong binding ability with TMV-CP; the malondialdehyde (MDA) and superoxide dismutase assay (SOD) activity measurements also fully confirmed that \u003cb\u003eL20\u003c/b\u003e stimulated the plant immune system and strengthened the plant's resistance to diseases by lowering the MDA content and increasing the SOD activity. In addition, the chlorophyll content test experiment found that \u003cb\u003eL20\u003c/b\u003e could reduce the destructive effect of viruses on chloroplasts, increase the content of chlorophyll, and promote photosynthesis. In conclusion, above experimental results suggested that flavonol derivatives containing benzothiazole could be further investigated as new plant virus antiviral drugs.\u003c/p\u003e","manuscriptTitle":"Novel flavonoid derivatives containing benzothiazole as potential antiviral agents: design, synthesis, and biological evaluation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-07 14:56:58","doi":"10.21203/rs.3.rs-5025191/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 7th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-23T13:38:44+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-07 14:56:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5025191","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5025191","identity":"rs-5025191","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}