Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease

…, K Appelt, JA Burgess, KM Campanale…

Index: Kaldor, Stephen W.; Kalish, Vincent J.; Davies II, Jay F.; Shetty, Bhasker V.; Fritz, James E.; Appelt, Krzysztof; Burgess, Jeffrey A.; Campanale, Kristina M.; Chirgadze, Nickolay Y.; Clawson, David K.; Dressman, Bruce A.; Hatch, Steven D.; Khalil, Deborah A.; Kosa, Maha B.; Lubbehusen, Penny P.; Muesing, Mark A.; Patick, Amy K.; Reich, Siegfried H.; Su, Kenneth S.; Tatlock, John H. Journal of Medicinal Chemistry, 1997 , vol. 40, # 24 p. 3979 - 3985

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Citation Number: 433

Abstract

Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor (K i= 2 nM) and antiviral agent (HIV-1 ED50= 14 nM). An X-ray cocrystal structure of the enzyme-AG1343 complex reveals how the novel thiophenyl ether and phenol-amide ...