title: CoMFA and CoMSIA studies of angiotensin (AT1) receptor antagonists.
abstract: Two 3D-QSAR methods--CoMFA and CoMSIA--were applied to a set of 38 angiotensin receptor (AT1) antagonists. The conformation and alignment of molecules were obtained by a novel method - consensus dynamics. The representation of biological activity, partial charge formalism, absolute orientation of the molecules in the grid, and grid spacing were also studied for their effect on the CoMFA models. The models were thoroughly validated through trials using scrambled activities and bootstrapping. The best CoMFA model had a cross-validated correlation coefficient ( q2) of 0.632, which improved with "region focusing" to 0.680. This model had a "predictive" r2 of 0.436 on a test series that was unique and with little representation in the training set. Although the "predictive" r2 of the best CoMSIA model, which included steric, electrostatic, and hydrogen bond acceptor fields was higher than that of the best CoMFA model, the other statistical parameters like q2, r2, F value, and s were unsatisfactory. The contour maps generated using the best CoMFA model were used to identify the structural features important for biological activity in these compounds.
authors.affiliation: Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400 098, India.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Datar
authors.forename: Prashant
authors.initials: P
authors.lastname: Desai
authors.forename: Evans
authors.initials: E
authors.lastname: Coutinho
authors.forename: Krishna
authors.initials: K
authors.lastname: Iyer
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry* / Q000145:classification; D002942:Circular Dichroism; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1