Orally bioavailable nonpeptide vitronectin receptor antagonists containing 2-aminopyridine arginine mimetics.

R M Keenan, W H Miller, L S Barton, W E Bondinell, R D Cousins, D F Eppley, S M Hwang, C Kwon, M A Lago, T T Nguyen, B R Smith, I N Uzinskas, C C Yuan

Index: Bioorg. Med. Chem. Lett. 9(13) , 1801-6, (1999)

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Abstract

A peptide RGD analog containing a novel 2-aminopyridine arginine mimetic was discovered to have good affinity and selectivity for the vitronectin receptor. Incorporation of the 2-aminopyridine arginine mimetic into the 3-oxo-1,4-benzodiazepine-2-acetic acid integrin antagonist series led to novel and potent nonpeptide vitronectin receptor antagonists with promising levels of oral bioavailability.