Nonpeptide αvβ3 Antagonists. 1. Transformation of a Potent, Integrin-Selective αIIbβ3 Antagonist into a Potent αvβ3 Antagonist
Journal of Medicinal Chemistry2000Vol. 43(20), pp. 3736–3745
Citations Over TimeTop 15% of 2000 papers
Mark E. Duggan, Le T. Duong, John Fisher, Terence G. Hamill, William F. Hoffman, Joel R. Huff, Nathan C. Ihle, Chih‐Tai Leu, Rose Marie Nagy, James J. Perkins, Sevgi B. Rodan, Gregg Wesolowski, David B. Whitman, Amy E. Zartman, Gideon A. Rodan, George D. Hartman
Abstract
Modification of the potent fibrinogen receptor (alpha(IIb)beta(3)) antagonist 1 generated compounds with high affinity for the vitronectin receptor alpha(v)beta(3). Sequential modification of the basic N-terminus of 1 led to the identification of the 5,6,7, 8-tetrahydro[1,8]naphthyridine moiety (THN) as a lipophilic, moderately basic N-terminus that provides molecules with excellent potency and selectivity for the integrin receptor alpha(v)beta(3). The THN-containing analogue 5 is a potent inhibitor of bone resorption in vitro and in vivo. In addition, the identification of a novel, nonpeptide radioligand with high affinity to alpha(v)beta(3) is also reported.
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