Structure-based design of nonpeptidic HIV protease inhibitors: the sulfonamide-substituted cyclooctylpyranones

…, DJ Anderson, RJ Reischer, TM Schwartz…

Index: Skulnick, Harvey I.; Johnson, Paul D.; Aristoff, Paul A.; Morris, Jeanette K.; Lovasz, Kristine D.; Howe, W. Jeffrey; Watenpaugh, Keith D.; Janakiraman, Musiri N.; Anderson, David J.; Reischer, Robert J.; Schwartz, Theresa M.; Banitt, Lee S.; Tomich, Paul K.; Lynn, Janet C.; Horng, Miao-Miao; Chong, Kong-Teck; Hinshaw, Roger R.; Dolak, Lester A.; Seest, Eric P.; Schwende, Francis J.; Rush, Bob D.; Howard, Gina M.; Toth, Lisa N.; Wilkinson, Karen R.; Kakuk, Thomas J.; Johnson, Carol W.; Cole, Serena L.; Zaya, Renee M.; Zipp, Gail L.; Possert, Peggy L.; Dalga, Robert J.; Zhong, Wei-Zhu; Williams, Marta G.; Romines, Karen R. Journal of Medicinal Chemistry, 1997 , vol. 40, # 7 p. 1149 - 1164

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Citation Number: 100

Abstract

Recently, cyclooctylpyranone derivatives with m-carboxamide substituents (eg 2c) were identified as potent, nonpeptidic HIV protease inhibitors, but these compounds lacked significant antiviral activity in cell culture. Substitution of a sulfonamide group at the meta position, however, produces compounds with excellent HIV protease binding affinity and antiviral activity. Guided by an iterative structure-based drug design process, we have ...