Comparative molecular field analysis (CoMFA) of phthalazine derivatives as phosphodiesterase IV inhibitors.
A comparative molecular field analysis (CoMFA) of phthalazine class of phosphodiesterase IV (PDE IV) inhibitors has been performed to correlate their chemical structures with their observed biological activity. A statistically valid model with good correlative and predictive power is reported. The leave one out cross-validation study gave cross-validation r(2)(cv) of value 0.507 at six optimum components and conventional r(2) of value 0.98. The predictive ability of the model was tested by predicting the seven molecules belonging to the test set giving predictive correlation coefficient of 0.59. This model is potentially helpful in the design of novel and more potent PDE IV inhibitors.
Chakraborti
Asit K
AK
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar 160 062, Punjab, India. akchakraborti@niper.ac.in
Gopalakrishnan
B
B
Sobhia
M Elizabeth
ME
Malde
Alpeshkumar
A
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D016208:Databases, Factual; D016018:Least-Squares Analysis; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D010793:Phthalazines / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
D010726:Phosphodiesterase Inhibitors; D010793:Phthalazines; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4