Synthesis and evaluation of 2-substituted-6-phenyl-4,5-dihydropyridazin-3(2H)-ones as potent inodilators.
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).
Kumar
Dinesh
D
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
Carron
Rosalia
R
La Calle
Carmen De
CD
Jindal
Dharam Paul
DP
Bansal
Ranju
R
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
D011724:Pyridazines; D014665:Vasodilator Agents