基于1,5-二芳基吡唑的胆囊收缩素1型受体拮抗剂的构效关系研究

SAR studies of 1,5-diarylpyrazole-based CCK1 receptor antagonists.

作者信息

Gomez Laurent, Hack Michael D, McClure Kelly, Sehon Clark, Huang Liming, Morton Magda, Li Lina, Barrett Terrance D, Shankley Nigel, Breitenbucher J Guy

机构信息

Johnson & Johnson Pharmaceutical Research and Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.

出版信息

Bioorg Med Chem Lett. 2007 Dec 1;17(23):6493-8. doi: 10.1016/j.bmcl.2007.09.093. Epub 2007 Oct 1.

DOI:10.1016/j.bmcl.2007.09.093

PMID:17933530

Abstract

A high throughput screening campaign revealed compound 1 as a potent antagonist of the human CCK(1) receptor. Here, we report the syntheses and SAR studies of 1,5-diarylpyrazole analogs with various structural modifications of the alkane side chain of the molecule. The difference in affinity between the two enantiomers for the CCK(1) receptor and the flexible nature of the linker led to the design of constrained analogs with increased potency.

摘要

一项高通量筛选活动表明化合物1是一种有效的人CCK(1)受体拮抗剂。在此，我们报告了对分子烷烃侧链进行各种结构修饰的1,5-二芳基吡唑类似物的合成及构效关系研究。两种对映体对CCK(1)受体的亲和力差异以及连接子的柔性促使我们设计出活性增强的受限类似物。