2-苯胺基-3-苯基磺酰基-6-甲基吡啶作为促肾上腺皮质激素释放因子1受体配体的合成与评价

Synthesis and evaluation of 2-anilino-3-phenylsulfonyl-6-methylpyridines as corticotropin-releasing factor1 receptor ligands.

作者信息

Hartz Richard A, Arvanitis Argyrios G, Arnold Charles, Rescinito Joseph P, Hung Kimberly L, Zhang Ge, Wong Harvey, Langley David R, Gilligan Paul J, Trainor George L

机构信息

Discovery Chemistry, Bristol-Myers Squibb Company, Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA.

出版信息

Bioorg Med Chem Lett. 2006 Feb 15;16(4):934-7. doi: 10.1016/j.bmcl.2005.10.097. Epub 2005 Nov 16.

DOI:10.1016/j.bmcl.2005.10.097

PMID:16297619

Abstract

A novel series of 2-anilino-3-phenylsulfonyl-6-methylpyridines was synthesized and evaluated as corticotropin-releasing factor receptor ligands. Structure-activity relationship studies focused primarily on optimization of the 3-phenylsulfonyl group. Compounds within this series were identified which showed potent binding affinity for the CRF1 receptor. Selected compounds were examined in a rat pharmacokinetic study and were found to have oral bioavailabilities ranging from 16 to 35%.

摘要

合成了一系列新型的2-苯胺基-3-苯基磺酰基-6-甲基吡啶，并将其作为促肾上腺皮质激素释放因子受体配体进行评估。构效关系研究主要集中在3-苯基磺酰基的优化上。该系列中的化合物被鉴定出对CRF1受体具有强效结合亲和力。对选定的化合物进行了大鼠药代动力学研究，发现其口服生物利用度在16%至35%之间。