Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
J Med Chem ; 53(2): 607-15, 2010 Jan 28.
Article in English | MEDLINE | ID: mdl-19961222

ABSTRACT

By a small modification in the core structure of the previously reported series of HIV-1 protease inhibitors that encompasses a tertiary alcohol as part of the transition-state mimicking scaffold, up to 56 times more potent compounds were obtained exhibiting EC(50) values down to 3 nM. Three of the inhibitors also displayed excellent activity against selected resistant isolates of HIV-1. The synthesis of 25 new and optically pure HIV-1 protease inhibitors is reported, along with methods for elongation of the inhibitor P1' side chain using microwave-accelerated, palladium-catalyzed cross-coupling reactions, the biological evaluation, and X-ray data obtained from one of the most potent analogues cocrystallized with both the wild type and the L63P, V82T, I84 V mutant of the HIV-1 protease.


Subject(s)
Alcohols/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/chemical synthesis , HIV Protease Inhibitors/chemical synthesis , Alcohols/pharmacology , Antiviral Agents/pharmacology , Crystallography, X-Ray , HIV Protease/genetics , HIV Protease Inhibitors/chemistry , HIV Protease Inhibitors/pharmacology , HIV-1/genetics , Inhibitory Concentration 50 , Molecular Mimicry , Mutation, Missense
SELECTION OF CITATIONS
SEARCH DETAIL
...