title: Rational design, synthesis and 2D-QSAR study of novel vasorelaxant active benzofuran-pyridine hybrids.
abstract: 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).
authors.affiliation: Therapeutical Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt. Electronic address: aladdinsrour@gmail.com.
authors.forename: Aladdin M
authors.initials: AM
authors.lastname: Srour
authors.affiliation: Therapeutical Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt.
authors.forename: Somaia S
authors.initials: SS
authors.lastname: Abd El-Karim
authors.affiliation: Pharmacology Department, National Research Centre, Dokki, Cairo 12622, Egypt.
authors.forename: Dalia O
authors.initials: DO
authors.lastname: Saleh
authors.affiliation: Pharmacology Department, National Research Centre, Dokki, Cairo 12622, Egypt.
authors.forename: Wafaa I
authors.initials: WI
authors.lastname: El-Eraky
authors.affiliation: Therapeutical Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt.
authors.forename: Zeinab M
authors.initials: ZM
authors.lastname: Nofal
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001572:Benzofurans / Q000737:chemistry* / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001572:Benzofurans; D011725:Pyridines; D014665:Vasodilator Agents
keywords: Amiodarone; Benzofuran; Pyridinecarbonitrile; QSAR; Vasodilator