Substituted 3-imidazo[1,2-a]pyridin-3-yl-4-(1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as highly selective and potent inhibitors of glycogen synthase kinase-3

被引：93

作者：

Engler, TA ^{[1
]}

Henry, JR ^{[1
]}

Malhotra, S ^{[1
]}

Cunningham, B ^{[1
]}

Furness, K ^{[1
]}

Brozinick, J ^{[1
]}

Burkholder, TP ^{[1
]}

Clay, MP ^{[1
]}

Clayton, J ^{[1
]}

Diefenbacher, C ^{[1
]}

Hawkins, E ^{[1
]}

Iversen, PW ^{[1
]}

Li, YH ^{[1
]}

Lindstrom, TD ^{[1
]}

Marquart, AL ^{[1
]}

McLean, J ^{[1
]}

Mendel, D ^{[1
]}

Misener, E ^{[1
]}

Briere, D ^{[1
]}

O'Toole, JC ^{[1
]}

Porter, WJ ^{[1
]}

Queener, S ^{[1
]}

Reel, JK ^{[1
]}

Owens, RA ^{[1
]}

Brier, RA ^{[1
]}

Eessalu, TE ^{[1
]}

Wagner, JR ^{[1
]}

Campbell, RM ^{[1
]}

Vaughn, R ^{[1
]}

机构：

[1] Lilly Res Labs, Indianapolis, IN 46285 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 16期

关键词：

D O I：

10.1021/jm049768a

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Glycogen synthase kinase-3 (GSK3) is involved in signaling from the insulin receptor. Inhibitors of GSK3 are expected to effect lowering of plasma glucose similar to insulin, making GSK3 an attractive target for the treatment of type 2 diabetes. Herein we report the discovery of a series of potent and selective GSK3 inhibitors. Compounds 7-12 show oral activity in an in vivo model of type II diabetes, and 9 and 12 have desirable PK properties.

引用

页码：3934 / 3937

页数：4

共 29 条

[1]

ALAWAR RS, 2001, Patent No. 2001044235

[2]

ALAWAR RS, 2004, IN PRESS BIOORG MED

[3] Glycogen synthase kinase-3: Properties, functions, and regulation [J].