Bioorg Med Chem. 2010 Jun 1;18(11):3841-59. Epub 2010 Apr 20.

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

Kobayashi T, Sasaki S, Tomita N, Fukui S, Kuroda N, Nakayama M, Kiba A, Takatsu Y, Ohtaki T, Itoh F, Baba A.

Source

Takeda Pharmaceutical Company, Ltd, Ibaraki 300-4293, Japan. Kobayashi_Toshitake@takeda.co.jp

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.

PMID:: 20457527; [PubMed - indexed for MEDLINE]

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