Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold

Article ID	Journal	Published Year	Pages	File Type
7802612	European Journal of Medicinal Chemistry	2012	13 Pages	PDF

Abstract

âº THIQ3CA analogs possess excellent direct FXa inhibition property. âº A potent dicarboxamide 47 displays Ki of 135Â nM âº An additive relationship between two arms on the THIQ3CA core led to the design of 47. âº The inhibitors were assembled in only three high yielding steps. âº 47 displays >1852-fold selectivity for FXa inhibition over other coagulation enzymes.

Keywords

APTT FXa FIIa THIQ 1,2,3,4-tetrahydroisoquinoline 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Structure–activity relationships activated partial thromboplastin time prothrombin time Hill slope Anticoagulant Factor Xa Phenylalanine