Acta Pharm. 58 (2008) 393-405
Original research paper
Synthesis
and evaluation of 2-substituted-6-phenyl-4,5-dihydropyridazin-3(2H)-ones as potent inodilators
DINESH KUMAR, ROSALIA CARRON, CARMEN DE LA CALLE, DHARAM PAUL JINDAL and
RANJU BANSAL
ranju29in@yahoo.co.in
University Institute of
Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India
Departamento
de Fisiología y Farmacología, Facultad d Farmacia, Campus "Miguel de
Unamuno" E-37007 Salamanca, Spain
Accepted September 11, 2008
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 acieved by
Friedel-Crafts acylation of an 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 μmol L-1).
Keywords: pyridazinones, anilides, hydrazine derivatives, cardiotonic
activity, vasodilatory activity