人白细胞弹性蛋白酶的抑制作用。1. C-7-取代头孢菌素叔丁酯的抑制作用。

Inhibition of human leukocyte elastase. 1. Inhibition by C-7-substituted cephalosporin tert-butyl esters.

作者信息

Doherty J B, Ashe B M, Barker P L, Blacklock T J, Butcher J W, Chandler G O, Dahlgren M E, Davies P, Dorn C P, Finke P E

机构信息

Department of Medicinal Chemical Research, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.

出版信息

J Med Chem. 1990 Sep;33(9):2513-21. doi: 10.1021/jm00171a028.

DOI:10.1021/jm00171a028

PMID:2391691

Abstract

Time-dependent inhibitors of the enzyme human leukocyte elastase have been developed based on the cephem nucleus. A series of cephalosporin tert-butyl esters has been examined, and the activity of these compounds has been found to be very sensitive to C-7 substituents, with small, alpha-oriented, electron-withdrawing groups showing greatest activity. Additionally, the oxidation state of the sulfur atom has been found to play a role in potency, with sulfones showing considerably greater activity than the corresponding sulfides or beta-sulfoxides. The alpha-sulfoxides were inactive.

摘要

基于头孢烯核开发了人白细胞弹性蛋白酶的时间依赖性抑制剂。已对一系列头孢菌素叔丁酯进行了研究，发现这些化合物的活性对C-7取代基非常敏感，具有小的、α-取向的吸电子基团表现出最大活性。此外，已发现硫原子的氧化态在效力方面起作用，砜类显示出比相应的硫化物或β-亚砜类大得多的活性。α-亚砜类无活性。