Diaminopyrimidines, diaminopyridines and diaminopyridazines as histamine H4 receptor modulators

被引：4

作者：

Savall, Brad M. ^{[1
]}

Meduna, Steven P. ^{[1
]}

Tays, Kevin ^{[1
]}

Cai, Hui ^{[1
]}

Thurmond, Robin L. ^{[1
]}

McGovern, Patricia ^{[1
]}

Gaul, Michael ^{[1
]}

Zhao, Bao-Ping ^{[1
]}

Edwards, James P. ^{[1
]}

机构：

[1] Janssen Pharmaceut Res & Dev LLC, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 04期

关键词：

Histamine H-4; Antagonists; Pyrimidine; Pyridine; Pyridazine; ANTAGONISTS; LIGANDS;

D O I：

10.1016/j.bmcl.2014.12.027

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Previously disclosed H-4 receptor modulators, the triamino substituted pyridines and pyrimidines, contain a free primary amino (-NH2) group. In this Letter we demonstrate that an exocyclic amine (NH2) is not needed to maintain affinity, and also show a significant divergence in the SAR of the pendant diamine component. These des-NH2 azacycles also show a distinct functional spectrum, that appears to be influenced by the diamine component; in the case of the 1,3-amino pyrimidines, the preferred diamine is the amino pyrrolidine instead of the more common piperazines. Finally, we introduce 3,5-diamino pyridazines as novel histamine H-4 antagonists. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：956 / 959

页数：4

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