The synthesis and structure-activity relationship of 4-benzimidazolyl-piperidinylcarbonyl-piperidine analogs as histamine H3 antagonists

被引：6
作者：
Ting, Pauline C. [1 ]
Lee, Joe F. [1 ]
Albanese, Margaret M. [1 ]
Wu, Jie [1 ]
Aslanian, Robert [1 ]
Favreau, Leonard [2 ]
Nardo, Cymbelene [2 ]
Korfmacher, Walter A. [2 ]
West, Robert E. [3 ]
Williams, Shirley M. [3 ]
Anthes, John C. [3 ]
Rivelli, Maria A. [3 ]
Corboz, Michel R. [3 ]
Hey, John A. [3 ]
机构：
[1] Merck Res Labs, Dept Chem Res, Kenilworth, NJ 07033 USA
[2] Merck Res Labs, Dept Drug Metab, Kenilworth, NJ 07033 USA
[3] Merck Res Labs, Dept Biol Res, Kenilworth, NJ 07033 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 17期
关键词：
Histamine H-3 antagonist; RECEPTOR ANTAGONISTS; IDENTIFICATION; INHIBITION; DISORDERS; RELEASE; TARGET;
D O I：
10.1016/j.bmcl.2010.07.052
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A structure-activity relationship study of the lead piperazinylcarbonylpiperidine compound 3 resulted in the identification of 4-benzimidazolyl-piperidinylcarbonyl-piperidine 6h as a histamine-3 (H-3) receptor antagonist. Additional optimization of 6h led to the identification of compounds 11i-k with Ki <= 0.5 nM and good in vivo activity. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5004 / 5008
页数：5
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