From SAR to comparative QSAR: role of hydrophobicity in the design of 4-hydroxy-5,6-dihydropyran-2-ones HIV-1 protease inhibitors.
Role of hydrophobicity in the design of 4-hydroxy-5,6-dihydropyran-2-ones-a new class of emerging HIV-1 protease inhibitors (HIV-PI) was investigated by using comparative QSAR. These studies show that most of the data points in the individual dataset studied fall either on positive or negative side of the optimum value of ClogP. This is why, we observe either a positive or negative ClogP term in the QSAR. To observe the optimum value of ClogP for these inhibitors, a sufficient spread in the data is required. It is hoped that the results of this study would help in optimizing substituents for better binding at enzyme pockets and guide in the design of more effective HIV-PI of this class.
Bhhatarai
Barun
B
Department of Chemistry, Clarkson University, Potsdam, NY 13699-5810, USA.
Garg
Rajni
R
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D015195:Drug Design; D016333:HIV Protease / Q000737:chemistry; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D011714:Pyrans / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011714:Pyrans; D016333:HIV Protease