Synthesis, vasorelaxant activity and 2D-QSAR study of some novel pyridazine derivatives

• Some phenylpyridazines were prepared by facile methods.
• They were screened for their vasorelaxant activity.
• Compounds 8a and 11a revealed promising activity compared to doxazosin mesylate.
• A reliable 2D-QSAR model was obtained to validate the obtained results.

Novel 3,6-disubstituted pyridazines were synthesized by facile method and screened for their vasorelaxant properties utilizing isolated thoracic rat aortic rings. Compounds 8a and 11a exerted potent vasorelaxant activity (IC50 = 198 and 177 μM, respectively) relative to doxazosin mesylate (used reference standard, IC50 = 226 μM), that, they may represent promising hits for treatment of cardiovascular disorders. The observed activity was validated by a statistically significant QSAR model (N = 32, n = 6, R2 = 0.811782, R2cvOO = 0.7153, R2cvMO = 0.7209, F = 17.9708, s2 = 9.65226 × 10−8) that was obtained employing CODESSA-Pro software.

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