title: Synthesis and docking studies of new 1,4-dihydropyridines containing 4-(5)-Chloro-2-ethyl-5-(4)-imidazolyl substituent as novel calcium channel agonist.
abstract: 1,4-Dihydropyridines have been recognized as calcium channel agonist. Three new analogues of Bay K8644 in which the ortho trifluromethyl phenyl group at position 4 is replaced by the 4-(5)-Chloro-2-ethyl-5-(4)-imidazolyl substituent, were designed and synthesized as calcium channel agonist. For this propose, the structures of designed compounds were drawn by HYPERCHEM program. Conformations of the compounds were optimized through semi-empirical method followed by PM3 calculation. Then the crystalin stucture of L-type calcium channel was obtained from the Protein Data Bank (PDB) server. Docking calculations were carried out using Auto-Dock.4 program. The good interaction of our 1,4-DHP derivatives showed that they can be as possible calcium channel agonist agents. Finally compounds were synthesized according to a modified Hantzsch condensation procedure.
authors.affiliation: Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran. adavood2001@yahoo.com
authors.forename: Asghar
authors.initials: A
authors.lastname: Davood
authors.forename: Ali Reza
authors.initials: AR
authors.lastname: Nematollahi
authors.forename: Maryam
authors.initials: M
authors.lastname: Iman
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000138:chemical synthesis; D001665:Binding Sites; D002120:Calcium Channel Agonists / Q000138:chemical synthesis*; D015220:Calcium Channels / Q000737:chemistry* / Q000187:drug effects; D017076:Computer-Aided Design; D030562:Databases, Protein; D004095:Dihydropyridines / Q000138:chemical synthesis*; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D002120:Calcium Channel Agonists; D015220:Calcium Channels; D004095:Dihydropyridines; D008024:Ligands; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine