Hydrophobicity in the design of P2/P2' tetrahydropyrimidinone HIV protease inhibitors.
As part of an ongoing effort in understanding the role of hydrophobicity in the design of nonpeptidic HIV protease inhibitors, the QSAR study on P2/P2' tetrahydropyrimidinone is presented in this report. Our results suggest that the balance of hydrophobicity and a volume- dependent polarizability term plays a key role in the inhibition of the viral protease by these inhibitors. The size of the substituent of ligands at particular positions that induce steric fit is crucial. The role of hydrophobicity in the design of tetrahydropyrimidinone is discussed. It has been found that a sufficient spread in the data is required to observe the optimum value of ClogP for these inhibitors.
Department of Chemistry, Clarkson University, Potsdam, NY 13699-5810, USA. rgarg@clarkson.edu
Rajni
R
Garg
Disha
D
Patel
D015195:Drug Design; D016333:HIV Protease / Q000187:drug effects*; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008968:Molecular Conformation; D011744:Pyrimidinones / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
D017320:HIV Protease Inhibitors; D008024:Ligands; D011744:Pyrimidinones; C505709:tetrahydropyrimidinone; D016333:HIV Protease