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

Pauline C Ting; Joe F Lee; Margaret M Albanese; Jie Wu; Robert Aslanian; Leonard Favreau; Cymbelene Nardo; Walter A Korfmacher; Robert E West; Shirley M Williams; John C Anthes; Maria A Rivelli; Michel R Corboz; John A Hey

doi:10.1016/j.bmcl.2010.07.052

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

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5004-8. doi: 10.1016/j.bmcl.2010.07.052. Epub 2010 Jul 16.

Authors

Pauline C Ting¹, Joe F Lee, Margaret M Albanese, Jie Wu, Robert Aslanian, Leonard Favreau, Cymbelene Nardo, Walter A Korfmacher, Robert E West, Shirley M Williams, John C Anthes, Maria A Rivelli, Michel R Corboz, John A Hey

Affiliation

¹ Department of Chemical Research, Merck Research Laboratories, Kenilworth, NJ 07033, USA. [email protected]

PMID: 20685118
DOI: 10.1016/j.bmcl.2010.07.052

Abstract

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 K(i) <or= 0.5 nM and good in vivo activity.

MeSH terms

Histamine H3 Antagonists / chemical synthesis*
Histamine H3 Antagonists / pharmacology*
Piperidines / chemical synthesis*
Piperidines / pharmacology*
Structure-Activity Relationship

Substances

Histamine H3 Antagonists
Piperidines