A new class of HIV-1 protease inhibitors containing a tertiary alcohol in the transition-state mimicking scaffold
2005 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 48, no 25, 8098-8102 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2005. Vol. 48, no 25, 8098-8102 p.
Alcohols/*chemistry, Cell Line, Cell Membrane Permeability, Crystallography; X-Ray, Drug Resistance; Viral, HIV Protease/*chemistry/genetics/*metabolism, HIV Protease Inhibitors/*chemical synthesis/chemistry/pharmacology, HIV-1/drug effects/isolation & purification, Humans, Molecular Conformation, Molecular Mimicry, Mutation, Research Support; Non-U.S. Gov't, Stereoisomerism
IdentifiersURN: urn:nbn:se:uu:diva-75610DOI: 10.1021/jm050790tPubMedID: 16335934OAI: oai:DiVA.org:uu-75610DiVA: diva2:103521