A new class of HIV-1 protease inhibitors containing a tertiary alcohol in the transition-state mimicking scaffold

Jenny K Ekegren; Torsten Unge; Mayada Zreik Safa; Hans Wallberg; Bertil Samuelsson; Anders Hallberg

doi:10.1021/jm050790t

A new class of HIV-1 protease inhibitors containing a tertiary alcohol in the transition-state mimicking scaffold

J Med Chem. 2005 Dec 15;48(25):8098-102. doi: 10.1021/jm050790t.

Authors

Jenny K Ekegren¹, Torsten Unge, Mayada Zreik Safa, Hans Wallberg, Bertil Samuelsson, Anders Hallberg

Affiliation

¹ Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.

PMID: 16335934
DOI: 10.1021/jm050790t

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alcohols / chemistry*
Cell Line
Cell Membrane Permeability
Crystallography, X-Ray
Drug Resistance, Viral
HIV Protease / chemistry*
HIV Protease / genetics
HIV Protease / metabolism*
HIV Protease Inhibitors / chemical synthesis*
HIV Protease Inhibitors / chemistry
HIV Protease Inhibitors / pharmacology
HIV-1 / drug effects
HIV-1 / isolation & purification
Humans
Molecular Conformation
Molecular Mimicry
Mutation
Stereoisomerism

Substances

Alcohols
HIV Protease Inhibitors
HIV Protease