Dinesh Kumar, R. Carrón, Carmen De La Calle
Dec 1, 2008
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3
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Quality indicators
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Abstract
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 μmol L-1). Sinteza i farmakološko vrednovanje 2-supstituiranih-6-fenil-4,5-dihidropiridazin-3(2H)-ona kao snažnih srčanih stimulatora U radu je opisana sinteza i framakološko vrednovanje 2-supstituiranih-6-(4-acilaminofenil)-4,5-dihidropiridazin-3(2H)-ona kao snažnih srčanih stimulatora. Spojevi 2-4 i 7-11 sintetizirani su Friedel-Craftsovim acilaranjem odgovarajućeg anilida s anhidridom jantarne ili anhidridom metiljantarne kiseline te ciklizacijom intermedijarnih keto kiselina s različitim derivatima hidrazina. Kardiotonično djelovanje novosintetiziranih derivata piridazinona ispitano je na izoliranim atrijima štakora, a vazodilatirajuće djelovanje na silaznim torakalnim prstenima aorte prethodno kontrahiranim fenilefrinom (10-6 mol L-1). 6-(4-Metansulfonamidofenil)-2-fenil-4,5-dihidropiridazin-3(2H)-on (7) pokazao je značajno stimulativno i vazodilatirajuće djelovanje u nanomolarnim koncentracijama (IC50 = 0,08 ± 0,01 μmol L-1).