Rational design, synthesis and 2D-QSAR study of novel vasorelaxant active benzofuran-pyridine hybrids.
Reaction of 3-aryl-1-(benzofuran-2-yl)-2-propen-1-ones 3a-c with malononitrile in the presence of sufficient amount of sodium alkoxide in the corresponding alcohol proceeds in a regioselective manner to afford 2-alkoxy-4-aryl-6-(benzofuran-2-yl)-3-pyridinecarbonitriles 4-37, which also obtained by treating ylidenemalononitriles 6a-q with 2-acetylbenzofuran 1 in the presence of sufficient amount of sodium alkoxide in the corresponding alcohol. The new chemical entities showed significant vasodilation properties using isolated thoracic aortic rings of rats pre-contracted with norepinephrine hydrochloride standard technique. Compounds 11, 16, 21, 24 and 30 exhibited remarkable activity compared with amiodarone hydrochloride the reference standard used in the present study. CODESSA-Pro software was employing to obtain a statistically significant QSAR model describing the bioactivity of the newly synthesized analogs (N=31, n=5, R(2)=0.846, R(2)cvOO=0.765, R(2)cvMO=0.778, F=27.540. s(2)=0.002).
['Srour|Aladdin M|AM|', 'Abd El-Karim|Somaia S|SS|', 'Saleh|Dalia O|DO|', 'El-Eraky|Wafaa I|WI|', 'Nofal|Zeinab M|ZM|']
D000818:Animals D001013:Aorta, Thoracic D001572:Benzofurans D060326:Chemistry Techniques, Synthetic D015195:Drug Design D004353:Drug Evaluation, Preclinical D011725:Pyridines D021281:Quantitative Structure-Activity Relationship D051381:Rats D014664:Vasodilation D014665:Vasodilator Agents
Vasodilator Amiodarone QSAR Benzofuran Pyridinecarbonitrile