Thiazolo[5,4-f]quinazolin-9-ones, inhibitors of glycogen synthase kinase-3

被引：60

作者：

Testard, Alexandra

Loge, Cedric

Leger, Benoit

Robert, Jean-Michel

Lozach, Olivier

Blairvacq, Melina

Meijer, Laurent

Thiery, Valerie

Besson, Thierry

机构：

[1] Univ La Rochelle, UFR Sci Fondamentales & Sci Ingn, FRE CNRS 2766, Lab Biotechnol & Chim Bioorgan, F-17042 La Rochelle, France

[2] Univ Nantes, Nantes Atlantique Univ, Dept Pharmacochim, BioCiT EA 1155,UFR Sci Pharmaceut, F-44000 Nantes, France

[3] Biol Stn, Cell Cycle Grp, UMR7150, F-29682 Roscoff, France

[4] Biol Stn, UPS2682, F-29682 Roscoff, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 13期

关键词：

glycogen synthase kinase-3 inhibitors; quinazolines; microwave-assisted chemistry; molecular modeling;

D O I：

10.1016/j.bmcl.2006.04.006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In an effort to identify new protein kinase inhibitors with increased potency and selectivity, we have developed the microwave-assisted synthesis of thiazolo[5,4-f]quinazolin-9-ones. The effects of eighteen derivatives on CDK1/cyclin B, CDK5/p25, and GSK-3 were investigated. Several turned out to inhibit GSK-3 in the micromolar range. Molecular modeling studies suggest that the most selective GSK-3 inhibitors 7a-d bind into the ATP-binding site through a key hydrogen bond interaction with Val135 and target the specific hydrophobic backpocket of the enzyme. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：3419 / 3423

页数：5

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