Rational design, synthesis and 2D-QSAR study of novel vasorelaxant active benzofuran-pyridine hybrids

doi:10.1016/j.bmcl.2016.03.054

Bioorganic & Medicinal Chemistry Letters

Volume 26, Issue 10, 15 May 2016, Pages 2557-2561

https://doi.org/10.1016/j.bmcl.2016.03.054 Get rights and content

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, R² = 0.846, R²_cvOO = 0.765, R²_cvMO = 0.778, F = 27.540. s² = 0.002).

Graphical abstract

Some novel bezofuran-pyridinecarbonitrile hybrids as vasorelaxant active agents.

Section snippets

Acknowledgment

This work was supported financially by National Research Centre, Dokki, Cairo 12622, Egypt, (project No. 100-10-116).

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Rational design, synthesis and 2D-QSAR study of novel vasorelaxant active benzofuran-pyridine hybrids

Abstract

Graphical abstract

Section snippets

Acknowledgment

Bioorg. Med. Chem. Lett.

Tetrahedron Lett.

Arab. J. Chem.

Bioorg. Med. Chem.

Bioorg. Med. Chem. Lett.

Eur. J. Med. Chem.

Bioorg. Med. Chem. Lett.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Am. J. Med.

Toxicol. In Vitro

Bioorg. Med. Chem.

Eur. J. Med. Chem.

Phytomedicine

Bioorg. Med. Chem.

Eur. J. Med. Chem.

Chem. Pharm. Bull.

J. Nat. Prod.

Chem. Pharm. Bull.