title: Toward the identification of a reliable 3D QSAR pharmacophore model for the CCK2 receptor antagonism.
abstract: The present study describes application of computational approaches to identify a validated and reliable 3D QSAR pharmacophore model for the CCK-2R antagonism through integrated ligand and structure based studies using anthranilic sulfonamide and 1,3,4-benzotriazepine based CCK-2R antagonists. The best hypothesis consisted five features viz. two aliphatic hydrophobic, one aromatic hydrophobic, one H-bond acceptor, and one ring aromatic feature with an excellent correlation for 34 training set (r²(training) = 0.83) and 58 test set compounds (r²(test) = 0.74). This model was validated through F-test and docking studies at the active site of the plausible CCK-2R where the 99% significance and well corroboration with the pharmacophore model respectively describes the model's reliability. The model also predicts well to other known clinically effective CCK-2R antagonists. Therefore, the developed model may useful in finding new scaffolds that may aid in design and develop new chemical entities (NCEs) as potent CCK-2R antagonists before their synthesis.
authors.affiliation: Medicinal and Process Chemistry Division, C.S.I.R.-Central Drug Research Institute, Lucknow 226001, India.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Gupta
authors.forename: Kanika
authors.initials: K
authors.lastname: Varshney
authors.forename: Anil K
authors.initials: AK
authors.lastname: Saxena
mesh_terms: D001552:Benzazepines / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D043887:Receptor, Cholecystokinin B; D013449:Sulfonamides