Non-covalent thrombin inhibitors featuring P3-heterocycles with P1-bicyclic arginine surrogates

被引：21

作者：

Cui, JRJ ^{[1
]}

Araldi, GL ^{[1
]}

Reiner, JE ^{[1
]}

Reddy, KM ^{[1
]}

Kemp, SJ ^{[1
]}

Ho, JZ ^{[1
]}

Siev, DV ^{[1
]}

Mamedova, L ^{[1
]}

Gibson, TS ^{[1
]}

Gaudette, JA ^{[1
]}

Minami, NK ^{[1
]}

Anderson, SM ^{[1
]}

Bradbury, AE ^{[1
]}

Nolan, TG ^{[1
]}

Semple, JE ^{[1
]}

机构：

[1] Corvas Int Inc, Dept Med Chem, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(02)00585-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel, potent, and highly selective classes of thrombin inhibitors were identified, which resulted from judicious combination of P-4-aromatics and P-2-P-3-heterocyclic dipeptide surrogates with weakly basic (calcd pK(a) similar tonon-basic-8.6) bicyclic P-1-arginine mimics. The design, synthesis, and biological activity of achiral, non-covalent, orally bioavailable inhibitors NC1-NC44 featuring P-1-indazoles, benzimidazoles, indoles, benzotriazoles, and aminobenzisoxazoles is disclosed. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：2925 / 2930

页数：6

共 35 条

[1]

*ADV CHEM DEV INC, 2000, ACD CHEM SKETCH SOFT

[2] Bicyclic pyridones as potent, efficacious and orally bioavailable thrombin inhibitors [J].