Discovery of ritonavir, a potent inhibitor of HIV protease with high oral bioavailability and clinical efficacy

…, E McDonald, S Vasavanonda, A Saldivar…

Index: Kempf, Dale J.; Sham, Hing L.; Marsh, Kennan C.; Flentge, Charles A.; Betebenner, David; Green, Brian E.; McDonald, Edith; Vasavanonda, Sudthida; Saldivar, Ayda; Wideburg, Norman E.; Kati, Warren M.; Ruiz, Lisa; Zhao, Chen; Fino, Lynnmarie; Patterson, Jean; Molla, Akhteruzzaman; Plattner, Jacob J.; Norbeck, Daniel W. Journal of Medicinal Chemistry, 1998 , vol. 41, # 4 p. 602 - 617

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Citation Number: 168

Abstract

The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. ...