7-Phenyl-pyrido[2,3-d]pyrimidine-2,4-diamines: Novel and highly selective protein tyrosine phosphatase 1B inhibitors

被引：21

作者：

Cheung, Adrian Wai-Hing ^{[1
]}

Banner, Bruce ^{[1
]}

Bose, Jolly ^{[1
]}

Kim, Kyungjin ^{[1
]}

Li, Shiming ^{[1
]}

Marcopulos, Nicholas ^{[1
]}

Orzechowski, Lucja ^{[1
]}

Sergi, Joseph A. ^{[1
]}

Thakkar, Kshitij C. ^{[1
]}

Wang, Bing-Bing ^{[1
]}

Yun, Weiya ^{[1
]}

Zwingelstein, Catherine ^{[1
]}

Berthel, Steven ^{[1
]}

Olivier, Andree R. ^{[1
]}

机构：

[1] Hoffmann La Roche Inc, Roche Res Ctr, Nutley, NJ 07110 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 24期

关键词：

PTP1B inhibitor; Protein tyrosine phosphatase; Phosphatase selectivity; Pharmacokinetic; CONDENSED PYRIMIDINE SYSTEMS; INSULIN SENSITIVITY; OBESITY;

D O I：

10.1016/j.bmcl.2012.10.035

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

High throughput screening of the Roche compound collection led to the identification of diaminopyrroloquinazoline series as a novel class of PTP1B inhibitors. Structural modification of diaminopyrroloquinazoline series resulted in pyrido[2,3-d]pyrimidine-2,4-diamine series which was further optimized to give compounds 5 and 24 as potent, selective (except T-cell phosphatase) PTP1B inhibitors with good mouse PK properties. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：7518 / 7522

页数：5

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