活性位点导向的凝血酶抑制剂——II. 与精氨酸/胍生物电子等排体相关的研究。

Active site-directed thrombin inhibitors--II. Studies related to arginine/guanidine bioisosteres.

作者信息

St Laurent D R, Balasubramanian N, Han W T, Trehan A, Federici M E, Meanwell N A, Wright J J, Seiler S M

机构信息

Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660, USA.

出版信息

Bioorg Med Chem. 1995 Aug;3(8):1145-56. doi: 10.1016/0968-0896(95)00103-n.

DOI:10.1016/0968-0896(95)00103-n

PMID:7582986

Abstract

A series of N-arylsulfonylarginine amides was synthesized wherein the guanidine or arginine moiety was isosterically replaced by a number of heterocyclic functionalities. These compounds were evaluated as potential active-site inhibitors of thrombin. Bisamidines 11a-n showed a similar SAR to that of simple arginine compounds. The ex vivo clotting time measurement of 11d after ip dosing showed prolongation of clotting time in rats.

摘要

合成了一系列N-芳基磺酰基精氨酸酰胺，其中胍基或精氨酸部分被多种杂环官能团等排取代。这些化合物被评估为凝血酶潜在的活性位点抑制剂。双脒类化合物11a-n显示出与简单精氨酸化合物相似的构效关系。腹腔注射给药后11d的体内凝血时间测量显示大鼠凝血时间延长。