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• W2068469992 abstract "Recently, cyclooctylpyranone derivatives with m-carboxamide substituents (e.g. 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 prepared and evaluated a number of these derivatives, which are readily available via a seven-step synthesis. A few of the most potent compounds were further evaluated for such characteristics as pharmacokinetics and toxicity in rats and dogs. From this work, the p-cyanophenyl sulfonamide derivative 35k emerged as a promising inhibitor, was selected for further development, and entered phase I clinical trials." @default.
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• W2068469992 date "1997-03-01" @default.
• W2068469992 modified "2023-10-06" @default.
• W2068469992 title "Structure-Based Design of Nonpeptidic HIV Protease Inhibitors: The Sulfonamide-Substituted Cyclooctylpyranones" @default.
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• W2068469992 doi "https://doi.org/10.1021/jm960441m" @default.
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