title: Synthesis and evaluation of 2-substituted-6-phenyl-4,5-dihydropyridazin-3(2H)-ones as potent inodilators.
abstract: The present study describes the synthesis and pharmacological evaluation of 2-substituted-6-(4-acylaminophenyl)-4,5-dihydropyridazin-3(2H)-ones as potent inodilating agents. The synthesis of target compounds 2-4 and 7-11 was achieved by Friedel-Crafts acylation of appropriate anilide derivative with succinic anhydride or methylsuccinic anhydride and subsequent cyclization of intermediary keto acids with various hydrazine derivatives. The newly synthesized pyridazinone derivatives were evaluated for cardiotonic activity using isolated rat atria and for vasorelaxant activity using descending thoracic aortic rings of Wistar rats precontracted with phenylephrine (10-6 mol L-1). 6-(4-Methanesulfonamidophenyl)-2-phenyl-4,5-dihydropyridazin-3(2H)-one (7) exhibited significant inodilatory properties and showed vasorelaxant activity in a nanomolar range (IC50 = 0.08 +/- 0.01 mumol L-1).
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.forename: Rosalia
authors.initials: R
authors.lastname: Carron
authors.forename: Carmen De
authors.initials: CD
authors.lastname: La Calle
authors.forename: Dharam Paul
authors.initials: DP
authors.lastname: Jindal
authors.forename: Ranju
authors.initials: R
authors.lastname: Bansal
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D011724:Pyridazines; D014665:Vasodilator Agents