2003 Fused pyridine derivatives

Fused pyridine derivativesR 0450 Phenylbutyrates as Potent, Orally Bioavailable Vitronectin Receptor (Integrin

αvβ3) Antagonists. — Nonpeptide vitronectin receptor antagonists based on a phenyl-butyrate template are derived essentially from opening of the seven-membered ring of a potent lead. Phenylbutyrate (X) has very good affinity for αvβ3 and αvβ5, goodselectivity against αIIbβ3, and excellent pharmacokinetics. Additionally, (X) is a potent inhibitor of vascular smooth muscle cell migration in vitro. Compound (XII), bearing a methylaminopyridine subunit, shows promising results with respect to the αvβ3 binding assay, pharmacokinetics, and oral bioavailability. — (MILLER*, W. H.; et al.; Bioorg. Med. Chem. Lett. 13 (2003) 8, 1483-1486; GlaxoSmithKline Pharm., Collegeville, PA 19426, USA; Eng.) — H. Hoennerscheid

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