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Kubota D, Ishikawa M, Yamamoto M, Murakami S, Hachisu M, Katano K, Ajito K: Tricyclic pharmacophore-based molecules as novel integrin alpha (v) beta3 antagonists. Bioorg Med Chem. 2006 Apr 1;14(7):2089-108. Epub 2005 Nov 23.
Part 1: design and synthesis of a lead compound exhibiting alpha (v) beta3/alpha (IIb) beta3 dual antagonistic activity.. In order to generate novel compounds with integrin alpha (v) beta3-antagonistic activity together with antiplatelet activity, tricyclic pharmacophore-based molecules were designed and synthesized. Although piperazine-containing compounds initially prepared were selective alpha (IIb) beta3 antagonists, replacement of piperazine with piperidine furnished a potent alpha (v) beta3/alpha (IIb) beta3 dual antagonist. Structure-activity relationship (SAR) studies provided clues for further development of tricyclic pharmacophore-based integrin antagonists. |
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