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Discovery of 4-[(Z)-(4-Bromophenyl)- (ethoxyimino)methyl]-1‘-[(2,4-dimethyl-3- pyridinyl)carbonyl]-4‘-methyl-1,4‘- bipiperidine N-Oxide (SCH 351125):  An Orally Bioavailable Human CCR5 Antagonist for the Treatment of HIV Infection

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journal contribution
posted on 31.08.2001, 00:00 by Anandan Palani, Sherry Shapiro, John W. Clader, William J. Greenlee, Kathleen Cox, Julie Strizki, Michael Endres, Bahige M. Baroudy
Structure−activity studies on piperidino-piperidine 3 led to the discovery of SCH 351125 (1), a selective CCR5 antagonist with potent activity against RANTES binding (Ki = 2 nM), which possesses subnanomolar activity in blocking viral entry and has excellent antiviral potency versus a panel of primary HIV-1 viral isolates. Compound 1, which has good oral bioavailability in rats, dogs, and monkeys, is proposed as a potential therapeutic agent for the treatment of HIV-1 and has entered human clinical trials.

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