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

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

  • J Med Chem. 2005 Dec 29;48(26):8289-98. doi: 10.1021/jm0502081.
Jennifer D Venable 1,  Hui Cai,  Wenying Chai,  Curt A Dvorak,  Cheryl A Grice,  Jill A Jablonowski,  Chandra R Shah,  Annette K Kwok,  Kiev S Ly,  Barbara Pio,  Jianmei Wei,  Pragnya J Desai,  Wen Jiang,  Steven Nguyen,  Ping Ling,  Sandy J Wilson,  Paul J Dunford,  Robin L Thurmond,  Timothy W Lovenberg,  Lars Karlsson,  Nicholas I Carruthers,  James P Edwards
Affiliations

Affiliation

  • 1 Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, California 92121, USA. jvenable@prdus.jnj.com
PMID: 16366610 DOI: 10.1021/jm0502081
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.

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