脯氨酰内肽酶抑制剂的合成及其构效关系评估：犬脑脯氨酰内肽酶的体外抑制作用

Synthesis of prolyl endopeptidase inhibitors and evaluation of their structure-activity relationships: in vitro inhibition of prolyl endopeptidase from canine brain.

作者信息

Arai H, Nishioka H, Niwa S, Yamanaka T, Tanaka Y, Yoshinaga K, Kobayashi N, Miura N, Ikeda Y

机构信息

Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1993 Sep;41(9):1583-8. doi: 10.1248/cpb.41.1583.

DOI:10.1248/cpb.41.1583

PMID:8221972

Abstract

By chemical modification of a known prolyl endopeptidase (PEP) inhibitor (N-[N-(4-phenylbutanoyl)-L-prolyl]pyrrolidine; SUAM-1221), several arylalkanoyl derivatives (V-1--27) were synthesized and tested for in vitro inhibitory activity towards PEP from canine brain. Among them, 4-(2-thienyl)butanoyl derivatives (V-24--27) showed more potent PEP-inhibitory activity than SUAM-1221. The structure-activity relationships of these compounds are discussed.

摘要

通过对一种已知的脯氨酰内肽酶（PEP）抑制剂（N-[N-(4-苯基丁酰基)-L-脯氨酰基]吡咯烷；SUAM-1221）进行化学修饰，合成了几种芳基烷酰基衍生物（V-1至27），并测试了它们对犬脑PEP的体外抑制活性。其中，4-(2-噻吩基)丁酰基衍生物（V-24至27）表现出比SUAM-1221更强的PEP抑制活性。讨论了这些化合物的构效关系。