Tricyclic pharmacophore-based molecules as novel integrin αvβ3 antagonists. Part 1: Design and synthesis of a lead compound exhibiting αvβ3/ αIIbβ3 dual antagonistic activity

Dai Kubota, Minoru Ishikawa, Mikio Yamamoto, Shoichi Murakami, Mitsugu Hachisu, Kiyoaki Katano, Keiichi Ajito

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


In order to generate novel compounds with integrin α vβ3-antagonistic activity together with antiplatelet activity, tricyclic pharmacophore-based molecules were designed and synthesized. Although piperazine-containing compounds initially prepared were selective αIIbβ3 antagonists, replacement of piperazine with piperidine furnished a potent αvβ3/ αIIbβ3 dual antagonist. Structure-activity relationship (SAR) studies provided clues for further development of tricyclic pharmacophore-based integrin antagonists.

Original languageEnglish
Pages (from-to)2089-2108
Number of pages20
JournalBioorganic and Medicinal Chemistry
Issue number7
Publication statusPublished - 2006 Apr 1
Externally publishedYes


  • Acute ischemic disease
  • Integrin αβ antagonist
  • Integrin αβ antagonist
  • Non-peptide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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