title: CoMFA and CoMSIA 3D QSAR models for a series of some condensed thieno[2,3-d]pyrimidin-4(3H)-ones with antihistaminic (H1) activity.
abstract: Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies were carried out for a series of thienopyrimidines, novel Histamine H1 receptor antagonists. Various models were generated. The best predictive CoMFA model gave significant correlation coefficients (cross-validated r2 (q2) = 0.514, non-cross-validated r2 = 0.925), showing the influence of steric and electrostatic fields. Likewise, the best predictive CoMSIA model gave cross-validated r2 (q2) = 0.541, non-cross-validated r2 = 0.862, eliciting the influence of steric, electrostatic, hydrophobic and hydrogen bond acceptor fields. The generated models were externally validated and well correlated with calculated (predicted) and experimental inhibitory concentration (IC50) values, using test sets. The analysis of the contour maps of both CoMFA and CoMSIA models offer important structural insight for designing novel and more active Histamine H1 receptor antagonists prior to their synthesis.
authors.affiliation: Department of Pharmaceutical Chemistry, L.M. College of Pharmacy, Navrangpura, Gujarat, India. meenu1013@gmail.com
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Singh
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Singh
authors.forename: Mahesh T
authors.initials: MT
authors.lastname: Chhabria
authors.forename: Kamala
authors.initials: K
authors.lastname: Vasu
authors.forename: Dhaivat
authors.initials: D
authors.lastname: Pandya
mesh_terms: D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D008958:Models, Molecular; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D006633:Histamine Antagonists; D011744:Pyrimidinones; C542082:thieno(2,3-d)pyrimidin-4-one