Optimization of 2,4-diaminopyrimidines as GHS-R antagonists: Side chain exploration

被引：16

作者：

Liu, B ^{[1
]}

Liu, M ^{[1
]}

Xin, ZL ^{[1
]}

Zhao, HY ^{[1
]}

Serby, MD ^{[1
]}

Kosogof, C ^{[1
]}

Nelson, LTJ ^{[1
]}

Szczepankiewicz, BG ^{[1
]}

Kaszubska, W ^{[1
]}

Schaefer, VG ^{[1
]}

Falls, HD ^{[1
]}

Lin, CW ^{[1
]}

Collins, CA ^{[1
]}

Sham, HL ^{[1
]}

Liu, G ^{[1
]}

机构：

[1] Abbott Labs, Global Pharmaceut Res & Dev, Metab Dis Res, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 07期

关键词：

ghrelin; GHS-R antagonist; diaminopyrimidine; DHFR selectivity;

D O I：

10.1016/j.bmcl.2006.01.012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and structure-activity relationships of the 4- and 6-substituents of 2,4-diaminopyrimidine-based growth hormone secretagogue receptor (GHS-R) antagonists are described. Diaminopyrimidines with 6-norbornenyl (4n) and 6-tetrahydrofuranyl (4p) substitutents were found to exhibit potent GHS-R antagonism and good selectivity (similar to 1000-fold) against dihydrofolate reductase. (C) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1864 / 1868

页数：5

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