Discovery of a dihydropyrimidine series of molecules that selectively mimic the biological actions of calcitonin

被引：13

作者：

Matthews, JM ^{[1
]}

Liotta, F ^{[1
]}

Hageman, W ^{[1
]}

Rivero, RA ^{[1
]}

Westover, L ^{[1
]}

Yang, M ^{[1
]}

Xu, J ^{[1
]}

Demarest, K ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev, Drug Discovery, Spring House, PA 19477 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 05期

关键词：

calcitonin; dihydropyrimidine; GPCR;

D O I：

10.1016/j.bmcl.2003.12.071

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The use of a multiplex mimetic assay led us to identify 1,4-dihydropyrimidines with potent and selective calcitonin receptor mimetic activity. Subsequent modification of the clihydropyrimidine scaffold led to a series of molecules that were efficacious in a neonatal mouse calvaria in vitro model. Dihydropyrimidine 5h, in particular, was identified as a calcitonin mimetic (EC50 = 6 muM), active in-vivo in the Weanling rat model when administered subcutaneously. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：1155 / 1159

页数：5

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