title: 3-D-QSAR CoMFA and CoMSIA studies on tetrahydrofuroyl-L-phenylalanine derivatives as VLA-4 antagonists.
abstract: Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on tetrahydrofuroyl-L-phenylalanine derivatives as VLA-4 antagonists. The best CoMFA and CoMSIA models that were generated using atom based alignment from a training set of twenty five tetrahydrofuroyl-L-phenylalanine derivatives, are six-component models with good statistics; CoMFA: r(2)(cv)=0.366, r(2)=0.983, s=0.099, F=172.661 and PRESS=4.435; CoMSIA: r(2)(cv)=0.528, r(2)=0.995, s=0.054, F=577.87 and PRESS=3.563. Both of these 3-D-QSAR models were validated using a test set of eleven compounds, whose predicted pIC(50) values fall within one log unit of the actual pIC(50). The contour diagrams obtained for the various CoMFA and CoMSIA field contributions can be mapped back onto structural features to explain the activity trends of the molecules analysed. Based on the spatial arrangement of the various field contributions, novel molecules with improved activity can be designed.
authors.affiliation: Department of Molecular Modeling and Drug Design, Dr. Reddy's Laboratories Ltd, Discovery Research, Bollaram Road, Miyapur, 500 050, Hyderabad, India.
authors.forename: Akash
authors.initials: A
authors.lastname: Khandelwal
authors.forename: Ramamurthi
authors.initials: R
authors.lastname: Narayanan
authors.forename: Bulusu
authors.initials: B
authors.lastname: Gopalakrishnan
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity; D013237:Stereoisomerism
chemical_list: D004791:Enzyme Inhibitors; D005663:Furans; D039041:Integrin alpha4beta1; D010649:Phenylalanine