凝血酶抑制剂的设计与合成：含P1位精氨酸非极性替代物的MD805类似物

The design and synthesis of thrombin inhibitors: analogues of MD805 containing non-polar surrogates for arginine at the P1 position.

作者信息

Baettig U, Brown L, Brundish D, Dell C, Furzer A, Garman S, Janus D, Kane P D, Smith G, Walker C V, Cockcroft X, Ambler J, Mitchelson A, Talbot M D, Tweed M, Wills N

机构信息

Novartis Horsham Research Centre, West Sussex, UK.

出版信息

Bioorg Med Chem Lett. 2000 Jul 17;10(14):1563-6. doi: 10.1016/s0960-894x(00)00282-1.

DOI:10.1016/s0960-894x(00)00282-1

Abstract

A series of monocyclic and bicyclic amino acids have been synthesised and incorporated into thrombin inhibitors based on CGH728, an analogue of the Mitsubishi compound MD805. Benzthiazolylalanine (Bta) was found to be a good non-polar substitute for arginine at the P1 position, yielding compounds with low nanomolar potency and good selectivity for thrombin.

摘要

一系列单环和双环氨基酸已被合成，并基于三菱化合物MD805的类似物CGH728被纳入凝血酶抑制剂中。发现苯并噻唑基丙氨酸（Bta）是P1位精氨酸的良好非极性替代物，产生了具有低纳摩尔效力和对凝血酶良好选择性的化合物。

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