Six-membered cyclic ureas as HIV-1 protease inhibitors: a QSAR study based on CODESSA PRO approach. Quantitative structure-activity relationships

Alan R Katritzky; Alexander Oliferenko; Andre Lomaka; Mati Karelson

doi:10.1016/s0960-894x(02)00741-2

Six-membered cyclic ureas as HIV-1 protease inhibitors: a QSAR study based on CODESSA PRO approach. Quantitative structure-activity relationships

Bioorg Med Chem Lett. 2002 Dec 2;12(23):3453-7. doi: 10.1016/s0960-894x(02)00741-2.

Authors

Alan R Katritzky¹, Alexander Oliferenko, Andre Lomaka, Mati Karelson

Affiliation

¹ Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville 32611-7200, USA. katritzky@chem.ufl.edu

PMID: 12419382
DOI: 10.1016/s0960-894x(02)00741-2

Abstract

Quantitative structure-activity relationships (QSAR) for HIV-1 protease inhibitory activity of substituted tetrahydropyrimidinones have been produced using CODESSA PRO methodology and software. The best four-parameter equation (R(2)(cv)=0.847) allowed us to reveal two main structural factors which are strongly correlated with the title activity: molecular hydrophobicity and ability to form hydrogen bonds with the target enzyme.

MeSH terms

HIV Protease Inhibitors / chemistry*
HIV Protease Inhibitors / pharmacology*
HIV-1 / drug effects
HIV-1 / enzymology*
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Kinetics
Pyrimidinones / chemistry*
Pyrimidinones / pharmacology*
Quantitative Structure-Activity Relationship
Regression Analysis
Software
Urea / analogs & derivatives*
Urea / pharmacology

Substances

HIV Protease Inhibitors
Pyrimidinones
Urea