双吡咯并吡咯烯的化学修饰及构效关系。2. 1,11-环状类似物。

Chemical modification and structure-activity relationships of pyripyropenes. 2. 1,11-Cyclic analogs.

作者信息

Obata R, Sunazuka T, Kato Y, Tomoda H, Harigaya Y, Omura S

机构信息

Research Center for Biological Function, Kitasato Institute, Kitasato University, Tokyo, Japan.

出版信息

J Antibiot (Tokyo). 1996 Nov;49(11):1149-56. doi: 10.7164/antibiotics.49.1149.

DOI:10.7164/antibiotics.49.1149

PMID:8982344

Abstract

A series of 1,11-cyclic analogs of pyripyropene A were prepared. Replacement of the 1,11-acyl groups of pyripyropenes with 1,11-cyclic acetals effectively improved in vitro acyl CoA:cholesterol acyltransferase (ACAT) inhibitory activity. Especially noteworthy is benzylidene acetal analog 35, the most potent inhibitor (IC50 = 5.6 nM) among the derivatives prepared so far, which showed 16 times more potent inhibitory activity than pyripyropene A.

摘要

制备了一系列吡喃并吡咯菌素A的1,11-环类似物。用1,11-环缩醛取代吡喃并吡咯菌素的1,11-酰基可有效提高体外酰基辅酶A：胆固醇酰基转移酶（ACAT）的抑制活性。特别值得注意的是亚苄基缩醛类似物35，它是迄今为止制备的衍生物中最有效的抑制剂（IC50 = 5.6 nM），其抑制活性比吡喃并吡咯菌素A强16倍。