title: A new class of HIV-1 protease inhibitors containing a tertiary alcohol in the transition-state mimicking scaffold.
abstract: Novel HIV-1 protease inhibitors encompassing a tertiary alcohol as part of the transition-state mimicking unit have been synthesized. Variation of the P1'-P3' residues and alteration of the tertiary alcohol absolute stereochemistry afforded 10 inhibitors. High potencies for the compounds with (S)-configuration at the carbon carrying the tertiary hydroxyl group were achieved with Ki values down to 2.4 nM. X-ray crystallographic data for a representative compound in complex with HIV-1 protease are presented.
authors.affiliation: Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Jenny K
authors.initials: JK
authors.lastname: Ekegren
authors.forename: Torsten
authors.initials: T
authors.lastname: Unge
authors.forename: Mayada Zreik
authors.initials: MZ
authors.lastname: Safa
authors.forename: Hans
authors.initials: H
authors.lastname: Wallberg
authors.forename: Bertil
authors.initials: B
authors.lastname: Samuelsson
authors.forename: Anders
authors.initials: A
authors.lastname: Hallberg
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D002460:Cell Line; D002463:Cell Membrane Permeability; D018360:Crystallography, X-Ray; D024882:Drug Resistance, Viral; D016333:HIV Protease / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008968:Molecular Conformation; D018716:Molecular Mimicry; D009154:Mutation; D013237:Stereoisomerism
chemical_list: D000438:Alcohols; D017320:HIV Protease Inhibitors; D016333:HIV Protease