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Preparation and biological evaluation of indole, benzimidazole, and thienopyrrole piperazine carboxamides: potent human histamine h(4) antagonists.

Abstract：

:Three series of H(4) receptor ligands, derived from indoly-2-yl-(4-methyl-piperazin-1-yl)-methanones, have been synthesized and their structure-activity relationships evaluated for activity at the H(4) receptor in competitive binding and functional assays. In all cases, substitution of small lipophilic groups in the 4 and 5-positions led to increased activity in a [(3)H]histamine radiolabeled ligand competitive binding assay. In vitro metabolism and initial pharmacokinetic studies were performed on selected compounds leading to the identification of indole 8 and benzimidazole 40 as potent H(4) antagonists with the potential for further development. In addition, both 8 and 40 demonstrated efficacy in in vitro mast cell and eosinophil chemotaxis assays.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Venable JD,Cai H,Chai W,Dvorak CA,Grice CA,Jablonowski JA,Shah CR,Kwok AK,Ly KS,Pio B,Wei J,Desai PJ,Jiang W,Nguyen S,Ling P,Wilson SJ,Dunford PJ,Thurmond RL,Lovenberg TW,Karlsson L,Carruthers NI,Edwards JP

doi

10.1021/jm0502081

keywords:

subject

Has Abstract

pub_date

2005-12-29 00:00:00

pages

8289-98

issue

26

eissn

0022-2623

issn

1520-4804

journal_volume

48

pub_type

杂志文章

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