title: Facile synthesis, vasorelaxant properties and molecular modeling studies of 2-amino-8a-methoxy-4H-pyrano[3,2-c]pyridine-3-carbonitriles.
abstract: A facile synthetic approach towards 6-alkyl-2-amino-4-aryl-4a,5,6,7,8,8a-hexahydro-8a-methoxy-4H-pyrano[3,2-c]pyridine-3-carbonitriles 3a-n was reported via reaction of 1-alkyl-4-piperidones 1a,b with ylidenemalononitriles 2a-h in methanol in the presence of sufficient amount of sodium. The structure of 3 was established through different spectroscopic techniques and confirmed by single crystal X-ray studies. Vasodilation activities of the synthesized compounds were investigated in vitro using isolated thoracic aortic rings of Wister rats pre-contracted with norepinephrine hydrochloride standard method. All the prepared analogues exhibited considerable vasodilation properties especially, 3g and 3c which revealed the best vasodilation potency (IC50=0.30, 0.37 mM, respectively) among all the tested compounds. Molecular modeling studies, including fitting of the synthesized compounds to a 3D-pharmacophore and their docking into optimized homology model as α1-AR antagonists showed high docking score and fit values. The experimental vasodilation activities of compounds 3a-n are consistent with their molecular modeling results.
authors.affiliation: Pesticide Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt. girgisas10@yahoo.com
authors.forename: Adel S
authors.initials: AS
authors.lastname: Girgis
authors.forename: Nasser S M
authors.initials: NS
authors.lastname: Ismail
authors.forename: Hanaa
authors.initials: H
authors.lastname: Farag
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D011714:Pyrans; D011725:Pyridines; D014665:Vasodilator Agents