Synthesis and structure-activity relationships of 2-acylamino-4,6-diphenylpyridine derivatives as novel antagonists of GPR54

Toshitake Kobayashi, Kobayashi T, Satoshi Sasaki, Sasaki S, Tomita N, Naoki Tomita, Fukui S, Seiji Fukui, Kuroda N, Noritaka Kuroda, Masaharu Nakayama, Nakayama M, Atsushi Kiba, Kiba A, Yoshihiro Takatsu, Takatsu Y, Tetsuya Ohtaki, Ohtaki T, Itoh F, Fumio Itoh, Atsuo Baba, Baba A
Bioorganic & medicinal chemistry · 2010 · doi:10.1016/j.bmc.2010.04.036 · PMID:20457527
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Abstract

GPR54 is a G protein-coupled receptor (GPCR) which was formerly an orphan receptor. Recent functional study of GPR54 revealed that the receptor has an essential role to modulate sex-hormones including GnRH. Though antagonists of GPR54 are expected to be novel drugs for sex-hormone dependent diseases such as prostate cancer or endometriosis, small molecule GPR54 antagonists have not been reported. We have synthesized a series of 2-acylamino-4,6-diphenylpyridines to identify potent GPR54 antagonists. Detailed structure-activity relationship studies led to compound 9l with an IC(50) value of 3.7nM in a GPR54 binding assay, and apparent antagonistic activity in a cellular functional assay.
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Report error Found 42 Enz. Inhib. hit(s) with all data for entry = 50031869 Affinity DataIC50: 3.70nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 7.40nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 8nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 9.80nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 11nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 12nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 14nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 15nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 19nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 21nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 30nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 31nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 32nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 32nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 34nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 45nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 51nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 51nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 120nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 120nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 460nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 480nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 490nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 570nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 660nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 890nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 910nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 1.10E+3nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 1.20E+3nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 1.40E+3nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 1.50E+3nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 2.10E+3nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 2.50E+3nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 2.80E+3nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 3.60E+3nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 4.10E+3nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 5.10E+3nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 6.30E+3nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 9.90E+3nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 2.40E+4nMAssay Description:Antagonist activity at human GPR54 receptor expressed in CHO cells assessed as inhibition of metastin(40-54)-induced intracellular calcium mobilizati...More data for this Ligand-Target Pair Affinity DataIC50: 3.00E+4nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair Affinity DataIC50: 3.30E+4nMAssay Description:Displacement of [125I]metastin(40-54) from human GPR54 receptor expressed in CHO cells after 60 mins by scintillation countingMore data for this Ligand-Target Pair

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endometriosis

MeSH descriptors

Pyridines Pyridines Receptors, G-Protein-Coupled Animals CHO Cells Cricetinae Cricetulus Humans Inhibitory Concentration 50 Pyridines Pyridines Receptors, G-Protein-Coupled Receptors, G-Protein-Coupled Receptors, Kisspeptin-1 Structure-Activity Relationship

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