Nonpeptide αvβ3 antagonists. Part 11: discovery and preclinical evaluation of potent αvβ3 antagonists for the prevention and treatment of osteoporosis

…, BP Feuston, C Fernandez-Metzler…

Index: Coleman, Paul J; Brashear, Karen M; Askew, Ben C; Hutchinson, John H; McVean, Carol A; Duong; Feuston, Bradley P; Fernandez-Metzler, Carmen; Gentile, Michael A; Hartman, George D; Kimmel, Donald B; Leu, Chih-Tai; Lipfert, Lorraine; Merkle, Kara; Pennypacker, Brenda; Prueksaritanont, Thomayant; Rodan, Gideon A; Wesolowski, Gregg A; Rodan, Sevgi B; Duggan, Mark E Journal of medicinal chemistry, 2004 , vol. 47, # 20 p. 4829 - 4837

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Citation Number: 76

Abstract

3-(S)-Pyrimidin-5-yl-9-(5, 6, 7, 8-tetrahydro-[1, 8] naphthyridin-2-yl)-nonanoic acid (5e) and 3- (S)-(methylpyrimidin-5-yl)-9-(5, 6, 7, 8-tetrahydro-[1, 8] naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the αvβ3 receptor. These compounds have excellent in vitro profiles (IC50= 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus ...

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