N-[1-芳基-2-(1-咪唑基)乙基]胍衍生物作为牛线粒体F1F0 ATP水解酶的有效抑制剂。

N-[1-Aryl-2-(1-imidazolo)ethyl]-guanidine derivatives as potent inhibitors of the bovine mitochondrial F1F0 ATP hydrolase.

作者信息

Atwal Karnail S, Ahmad Saleem, Ding Charles Z, Stein Philip D, Lloyd John, Hamann Lawrence G, Green David W, Ferrara Francis N, Wang Paulina, Rogers W Lynn, Doweyko Lidia M, Miller Arthur V, Bisaha Sharon N, Schmidt Joan B, Li Ling, Yost Kenneth J, Lan Hsi-Jung, Madsen Cort S

机构信息

Department of Discovery Chemistry, Bristol-Myers Squibb, Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.

出版信息

Bioorg Med Chem Lett. 2004 Feb 23;14(4):1027-30. doi: 10.1016/j.bmcl.2003.11.077.

DOI:10.1016/j.bmcl.2003.11.077

PMID:15013016

Abstract

A series of substituted guanidine derivatives were prepared and evaluated as potent and selective inhibitors of mitochondrial F(1)F(0) ATP hydrolase. The initial thiourethane derived lead molecules possessed intriguing in vitro pharmacological profiles, though contained moieties considered non-drug-like. Analogue synthesis efforts led to compounds with maintained potency and superior physical properties. Small molecules in this series which potently and selectivity inhibit ATP hydrolase and not ATP synthase may have utility as cardioprotective agents.

摘要

制备了一系列取代胍衍生物，并将其作为线粒体F(1)F(0)ATP水解酶的强效和选择性抑制剂进行评估。最初的硫代氨基甲酸酯衍生先导分子具有引人注目的体外药理学特征，尽管含有被认为非药物样的部分。类似物合成工作产生了具有维持效力和优异物理性质的化合物。该系列中能够有效且选择性地抑制ATP水解酶而非ATP合酶的小分子可能具有作为心脏保护剂的用途。