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 ...

~98%

~56%

~46%

~99%

Concise Synthesis of 6-Cyanobenzo [b] furan, a Useful Buildi...

[Nguyen, Son T.; Williams, John D.; Majgier-Baranowska, Helena; Li, Bing; Neelagiri, Venugopal R.; Kim, Hwa-Ok; Peet, Norton P. Synthetic Communications, 2014 , vol. 44, # 9 p. 1307 - 1313]

Discovery and development of potent LFA-1/ICAM-1 antagonist ...

[Zhong, Min; Gadek, Thomas R.; Bui, Minna; Shen, Wang; Burnier, John; Barr, Kenneth J.; Hanan, Emily J.; Oslob, Johan D.; Yu, Chul H.; Zhu, Jiang; Arkin, Michelle R.; Evanchik, Marc J.; Flanagan, W. Mike; Hoch, Ute; Hyde, Jennifer; Prabhu, Saileta; Silverman, Jeffrey A.; Wright, Jasmin ACS Medicinal Chemistry Letters, 2012 , vol. 3, # 3 p. 203 - 206]

Syntheses of 5-and 6-[2, 3]-dihydrobenzofuran β-amino acids

[Coleman, Paul J.; Hutchinson, John H.; Hunt, Cecilia A.; Lu, Ping; Delaporte, Enock; Rushmore, Tom Tetrahedron Letters, 2000 , vol. 41, # 31 p. 5803 - 5806]