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

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Keyword

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

PHARMACY

FARMACI

Publication and Content Type

ref (subject category)

art (subject category)