From natural products to achiral drug prototypes: Potent thrombin inhibitors based on P2/P3 dihydropyrid-2-one core motifs

被引：10

作者：

Hanessian, Stephen ^{[1
]}

Therrien, Eric ^{[1
]}

Zhang, Jianbin ^{[1
]}

van Otterlo, Willem ^{[1
]}

Xue, Yafeng ^{[2
]}

Gustafsson, David ^{[3
]}

Nilsson, Ingemar ^{[4
]}

Fjellstrom, Ola ^{[5
]}

机构：

[1] Univ Montreal, Dept Chem, Montreal, PQ H3C 3J7, Canada

[2] AstraZeneca R&D, Cell Prot & Struct Sci, S-43183 Molndal, Sweden

[3] AstraZeneca R&D, Sci Advisory Grp, S-43183 Molndal, Sweden

[4] AstraZeneca R&D, Med Chem, S-43183 Molndal, Sweden

[5] AstraZeneca R&D, Lead Generat, S-43183 Molndal, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 18期

基金：

加拿大自然科学与工程研究理事会;

关键词：

Thrombin inhibitors; Dihydropyridone; STRUCTURAL CONFIRMATION; BLOOD-COAGULATION; DESIGN; ANTICOAGULANT; DYSINOSIN; ACETAMIDE; PROGRESS; FAMILY;

D O I：

10.1016/j.bmcl.2009.07.107

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of dihydropyrid-2-ones was synthesized and tested for inhibitory activity against serine protease enzymes. Moderate to low nanomolar inhibitory activities were obtained against thrombin and excellent selectivity against trypsin was observed. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5429 / 5432

页数：4

共 2 条

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