STRUCTURE-ACTIVITY-RELATIONSHIPS OF INHIBITORS DERIVED FROM 3-AMIDINOPHENYLALANINE

被引：28

作者：

STURZEBECHER, J ^{[1
]}

PRASA, D ^{[1
]}

WIKSTROM, P ^{[1
]}

VIEWEG, H ^{[1
]}

机构：

[1] PENTAPHARM LTD,CH-4002 BASEL,SWITZERLAND

来源：

JOURNAL OF ENZYME INHIBITION | 1995年 / 9卷 / 01期

关键词：

ENZYME INHIBITORS; THROMBIN INHIBITORS; 3-AMIDINOPHENYLALANINE; NAPAP;

D O I：

10.3109/14756369509040683

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：

Thrombin is the key enzyme in coagulation and its inhibitors are of therapeutic interest since they are potential anticoagulants. The most potent inhibitor of the benzamidine type is N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide (NAPAP). However, NAPAP and other substances designed so far do not fulfill the pharmacological requirements. The goal of designing new compounds was to obtain potent inhibitors with improved pharmacokinetic properties, such as absorption after oral application and a sustained elimination. Novel derivatives of 3-amidinophenylalanine as key building block were synthesized. The amidino moiety and both the N alpha- and the C-terminal substituents were widely varied. Some of the newly synthesized compounds are potent inhibitors of thrombin and exert improved pharmacokinetic properties.

引用

页码：87 / 99

页数：13

共 20 条

[1] CRYSTALLOGRAPHIC DETERMINATION OF THROMBIN COMPLEXES WITH SMALL SYNTHETIC INHIBITORS AS A STARTING POINT FOR THE RECEPTOR-BASED DESIGN OF ANTITHROMBOTICS [J].