Identification of an active metabolite of PAR-1 antagonist RWJ-58259 and synthesis of analogues to enhance its metabolic stability

被引：4

作者：

Robinson, Eifion ^{[1
]}

Knight, Emily ^{[1
]}

Smoktunowicz, Natalia ^{[2
]}

Chambers, Rachel C. ^{[2
]}

Inglis, Graham G. ^{[3
]}

Chudasama, Vijay ^{[1
]}

Caddick, Stephen ^{[1
]}

机构：

[1] UCL, Dept Chem, 20 Gordon St, London WC1H 0AJ, England

[2] Ctr Inflammat & Tissue Repair, 5 Univ St, London WC1E 6JJ, England

[3] GSK, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2016年 / 14卷 / 12期

基金：

英国工程与自然科学研究理事会;

关键词：

THROMBIN; RECEPTOR-1; POTENT; PHYSIOLOGY; DISCOVERY; DESIGN;

D O I：

10.1039/c6ob00332j

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The discontinuation of PAR-1 antagonist RWJ-58259 beyond use as a biological probe is most likely due to it's short half-life in vivo. However, retention of significant in vivo activity beyond the point where most of the RWJ-58259 had been consumed implies the generation of an active metabolite. Herein we describe the biological activity of a predicted metabolite of RWJ-58259 and the synthesis of analogues designed to enhance the metabolic stability of RWJ-58259.

引用

页码：3198 / 3201

页数：4