title: QSAR modelling of pancreatic beta-cell KATP channel openers R/S-3,4-dihydro-2,2-dimethyl-6-halo-4-(substituted phenylaminocarbonylamino)-2H-1-benzopyrans using MLR-FA techniques.
abstract: Potassium (K(+)) channel openers are a diverse group of compounds which are used for the treatment of diseases like angina pectoris, hypertension, congestive heart failure, anti-hypoglycemic (insulinoma), bronchial asthma, etc. R/S-3,4-dihydro-2,2-dimethyl-6-halo-4-(substituted phenylaminocarbonylamino)-2H-1-benzopyrans are a new series of ATP-sensitive potassium (K(ATP-pbeta)) channel openers selective towards pancreatic beta-cells. QSAR modelling was done on these series of compounds to find a more active and selective K(ATP-pbeta) channel opener selective towards beta-cells of pancreatic tissues. Wang-Ford charges, partition coefficient, molar refractivity, principle moment of inertia at X, Y and Z axes are used as predictor variables and logarithm of percentage of residual insulin secretion is treated as response variable for the modelling. Multiple linear regressions with factor analysis were performed to develop QSAR models. Four equations were obtained using different combinations of the predictor variables based on factor loadings. Regression coefficients of all descriptors used are significant at more than 95% level. Results showed that Wang-Ford charges on atom numbers 11, 17, 18, 19 and 21 are important for the inhibition of residual insulin secretion. The presence of electron withdrawing group at m- and p-position of phenyl ring B is required for the inhibition. The energy minimized geometry of the most active compound supported our modelling.
authors.affiliation: Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P.O. Box 17020, Jadavpur University, Kolkata 700 032, West Bengal, India.
authors.forename: Sk Mahasin
authors.initials: SM
authors.lastname: Alam
authors.forename: Soma
authors.initials: S
authors.lastname: Samanta
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Halder
authors.forename: Soumya
authors.initials: S
authors.lastname: Basu
authors.forename: Tarun
authors.initials: T
authors.lastname: Jha
mesh_terms: D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000737:chemistry*; D054086:KATP Channels / Q000819:agonists*; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
chemical_list: D001578:Benzopyrans; D054086:KATP Channels