组胺H3受体拮抗剂的4-[(1H-咪唑-4-基)甲基]哌啶系列中CYP450抑制作用的降低

Reduction of CYP450 inhibition in the 4-[(1H-imidazol-4-yl)methyl]piperidine series of histamine H3 receptor antagonists.

作者信息

Berlin Michael, Ting Pauline C, Vaccaro Wayne D, Aslanian Robert, McCormick Kevin D, Lee Joe F, Albanese Margaret M, Mutahi Mwangi W, Piwinski John J, Shih Neng-Yang, Duguma Luli, Solomon Daniel M, Zhou Wei, Sher Rosy, Favreau Leonard, Bryant Matthew, Korfmacher Walter A, Nardo Cymbelene, West Robert E, Anthes John C, Williams Shirley M, Wu Ren-Long, Susan She H, Rivelli Maria A, Corboz Michel R, Hey John A

机构信息

The Schering Plough Research Institute, 2015 Galloping Hill Rd. Kenilworth, NJ 07033, USA.

出版信息

Bioorg Med Chem Lett. 2006 Feb 15;16(4):989-94. doi: 10.1016/j.bmcl.2005.10.087. Epub 2005 Nov 15.

DOI:10.1016/j.bmcl.2005.10.087

PMID:16297617

Abstract

A novel series of histamine H3 receptor antagonists based on the 4-[(1H-imidazol-4-yl)methyl]piperidine template displaying low CYP2D6 and CYP3A4 inhibitory profiles has been identified. Structural features responsible for the reduction of P450 activity, a typical liability of 4-substituted imidazoles, have been established.

摘要

已鉴定出一系列基于4-[(1H-咪唑-4-基)甲基]哌啶模板的新型组胺H3受体拮抗剂，这些拮抗剂对CYP2D6和CYP3A4的抑制作用较低。已确定了导致P450活性降低的结构特征，P450活性降低是4-取代咪唑类药物的典型缺点。