Document Report Card

ID: ALA1141189

Journal: J Med Chem

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

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.

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.

CiteXplore: 16366610

DOI: 10.1021/jm0502081