title: Rational design, synthesis and QSAR study of vasorelaxant active 3-pyridinecarbonitriles incorporating 1H-benzimidazol-2-yl function.
abstract: A variety of 2-alkoxy-4-aryl-6-(1H-benzimidazol-2-yl)-3-pyridinecarbonitriles 4a-r were prepared via either regioselective reaction of 3-aryl-1-(1H-benzimidazol-2-yl)-2-propen-1-ones 3 with malononitrile or ylidenemalononitriles 6 with 2-acetyl-1H-benzimidazoles 1 in the presence of sodium alkoxide in the corresponding alcohol. All the synthesized compounds showed significant vasodilation properties using isolated thoracic aortic rings of rats pre-contracted with norepinephrine hydrochloride standard technique. Compounds 4d, 4p, 4l, and 4f exhibited remarkable activity compared with prazosin hydrochloride, which was used as a reference standard in the present study. QSAR studies revealed a good predictive and statistically significant 3 descriptor model (r(2) = 0.913, radjusted(2)=0.8808, rprediction(2)=0.7911).
authors: Therapeutical Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt.
authors: Zeinab M
authors: ZM
authors: Nofal
authors: Aladdin M
authors: AM
authors: Srour
authors: Wafaa I
authors: WI
authors: El-Eraky
authors: Dalia O
authors: DO
authors: Saleh
authors: Adel S
authors: AS
authors: Girgis
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001562:Benzimidazoles / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D066298:In Vitro Techniques; D008297:Male; D008956:Models, Chemical; D015394:Molecular Structure; D009638:Norepinephrine / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D001562:Benzimidazoles; D011725:Pyridines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009638:Norepinephrine; C020729:3-cyanopyridine