3D-QSAR studies on thieno[3,2-d]pyrimidines as phosphodiesterase IV inhibitors.
Cyclic nucleotide phosphodiesterase IV (PDE IV) inhibitors find utility in asthma and Chronic Obstructive Pulmonary Disease (COPD) therapy. A series of 29 thieno[3,2-d]pyrimidines with affinity for PDE IV was subjected to three dimensional quantitative structure activity relationship (3D-QSAR) studies using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Both CoMFA and CoMSIA provided statistically valid models with good correlative and predictive power. The incorporation of hydrophobic, hydrogen bond donor and hydrogen bond acceptor fields showed insignificant improvement in CoMSIA model. The 3D-QSAR models provide information for predicting the affinity of related compounds and designing more potent inhibitors.
Chakraborti
Asit K
AK
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), 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; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006844:Hydrocarbons, Cyclic / Q000737:chemistry / Q000494:pharmacology; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity; D013816:Thermodynamics
D004791:Enzyme Inhibitors; D006844:Hydrocarbons, Cyclic; D011743:Pyrimidines; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4