Abstract
A three-dimensional common feature pharmacophore model was developed using the X-ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs were designed and synthesized, having the benzimidazol-2-one system as a scaffold. Docking experiments showed that these molecules docked in a position and orientation similar to that of known inhibitors. Biological testing confirmed that our strategy was successful in searching for new leads as NNRTIs.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Anti-HIV Agents / chemical synthesis*
-
Anti-HIV Agents / chemistry
-
Anti-HIV Agents / pharmacology
-
Benzimidazoles / chemical synthesis*
-
Benzimidazoles / chemistry
-
Benzimidazoles / pharmacology
-
Binding Sites
-
Crystallography, X-Ray
-
HIV Reverse Transcriptase / chemistry*
-
HIV Reverse Transcriptase / metabolism
-
Humans
-
Models, Molecular
-
Reverse Transcriptase Inhibitors / chemical synthesis*
-
Reverse Transcriptase Inhibitors / chemistry
-
Reverse Transcriptase Inhibitors / pharmacology
-
Structure-Activity Relationship
-
Thiazoles / chemical synthesis*
-
Thiazoles / chemistry
-
Thiazoles / pharmacology
Substances
-
Anti-HIV Agents
-
Benzimidazoles
-
Reverse Transcriptase Inhibitors
-
Thiazoles
-
HIV Reverse Transcriptase