title: Synthesis, vasorelaxant activity and 2D-QSAR study of some novel pyridazine derivatives.
abstract: 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, R(2) = 0.811782, R(2)cvOO = 0.7153, R(2)cvMO = 0.7209, F = 17.9708, s(2) = 9.65226 × 10(-8)) that was obtained employing CODESSA-Pro software.
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, ElKasr El-Aini Street, 11562 Cairo, Egypt. Electronic address: rihamfgeorge@yahoo.com.
authors.forename: Riham F
authors.initials: RF
authors.lastname: George
authors.affiliation: Pharmacology Department, National Research Centre, Dokki, Giza 12622, Egypt.
authors.forename: Dalia O
authors.initials: DO
authors.lastname: Saleh
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar; D012984:Software; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D011724:Pyridazines; D014665:Vasodilator Agents
keywords: Pyridazines; QSAR; Vasodilator