ACTIVE-SITE-DIRECTED THROMBIN INHIBITORS - ALPHA-HYDROXYACYLPROLYL-ARGINALS - NEW ORALLY-ACTIVE STABLE ANALOGS OF D-PHE-PRO-ARG-H

被引：11

作者：

BAJUSZ, S ^{[1
]}

BARABAS, E ^{[1
]}

FAUSZT, I ^{[1
]}

FEHER, A ^{[1
]}

HORVATH, G ^{[1
]}

JUHASZ, A ^{[1
]}

SZABO, AG ^{[1
]}

SZELL, E ^{[1
]}

机构：

[1] INST DRUG RES,H-1325 BUDAPEST,HUNGARY

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1995年 / 3卷 / 08期

关键词：

D O I：

10.1016/0968-0896(95)00108-S

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

D-alpha-Hydroxyacyl-prolyl-arginals have been designed and synthesized as orally active stable analogs of D-Phe-Pro-Arg-H, the active site-directed peptidyl thrombin inhibitor prototype. Many of the new analogs possess high in vitro anticoagulant activity while having little effect on fibrinolysis. Compounds GYKI-66104 (2), -66131 (3) and -66132 (5) effectively delay the clotting time in rabbits ex vivo and prevent thrombus formation in various thrombosis models in rabbits and rats when applied in a single oral dose of 5 mg kg(-1).

引用

页码：1079 / 1089

页数：11

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