Quantitative structure activity relationship studies of aryl heterocycle-based thrombin inhibitors.
A quantitative structure activity relationship (QSAR) analysis has been performed on a data set of 42 aryl heterocycle-based thrombin inhibitors. Several types of descriptors including topological, spatial, thermodynamic, information content and E-state indices were used to derive a quantitative relationship between the anti thrombin activity and structural properties. Genetic algorithm based genetic function approximation method of variable selection was used to generate the model. Best model was developed when number of descriptors in the equation was set to five. Highly statistically significant model was obtained with atom type logP descriptors, logP and Shadow_YZ. The model is not only able to predict the activity of new compounds but also explained the important regions in the molecules in a quantitative manner.
Deswal
Sumit
S
Pharmacoinformatics division National Institute of Pharmaceutical Education and Research, Sector 67, Phase X, 160062 SAS Nagar, Punjab, India.
Roy
Nilanjan
N
D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011719:Pyrazines / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D004791:Enzyme Inhibitors; D011719:Pyrazines; D011725:Pyridines; D013917:Thrombin