Abstract
Using a training set of diketo-like acid HIV-1 integrase (IN) strand-transfer inhibitors, a 3D pharmacophore model was derived having quantitative predictive ability in terms of activity. The best statistical hypothesis consisted of four features (one hydrophobic aromatic region, two hydrogen-bond acceptors, and one hydrogen-bond donor) with r of 0.96. The resulting pharmacophore model guided the rational design of benzylindoles as new potent IN inhibitors, whose microwave-assisted synthesis and biological evaluation are reported.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Anti-HIV Agents / chemical synthesis*
-
Anti-HIV Agents / chemistry
-
Anti-HIV Agents / pharmacology
-
Binding Sites
-
Cell Line
-
Cytopathogenic Effect, Viral
-
Drug Design
-
HIV Integrase / chemistry*
-
HIV Integrase Inhibitors / chemical synthesis*
-
HIV Integrase Inhibitors / chemistry
-
HIV Integrase Inhibitors / pharmacology
-
Humans
-
Keto Acids / chemical synthesis*
-
Keto Acids / chemistry
-
Keto Acids / pharmacology
-
Lymphocytes / drug effects
-
Lymphocytes / virology
-
Models, Molecular
-
Quantitative Structure-Activity Relationship
Substances
-
Anti-HIV Agents
-
HIV Integrase Inhibitors
-
Keto Acids
-
HIV Integrase