Abstract

The 1,3-dipolar cycloaddition of N-aryl-C-ethoxycarbonylnitrile imines to pyridazin-3-thione afforded novel spirothiadiazolopyridazines in moderate to good yields. The reaction occurs regioselectively at the exocyclic C=S bond. Some of the newly synthesized compounds were tested for their in vitro antitumor activity against three human and murine cell lines [human: A2780, (ovary, carcinoma), A549 (lung, carcinoma); murine: P388 (leukaemia)]. Among the series, some compounds exhibited significant growth inhibitory effects against cell lines P388.

Keywords: Pyridazinethione, Spirothiadiazolopyridazine, Cytotoxic activity, N-aryl-C-ethoxycarbonylnitrile imines, pyridazin-3-thione, 1,3-dipolar cycloaddition, C NMR, Antiproliferative Activity, A2780, A549, P388, Perkin-Elmer Sciex API 3000 spectrometer, Thin-layer chromatography, TLC, 6-Methy-2-phenyl-4,5-dihydro-2H-pyridazin-3-thione 4, General Procedure for the Synthesis of Spirothiadia-zolopyridazines 7, 3'-Ethoxycarbonyl-6-methyl-1'-(p-Chlorophenyl)spiro[1' H-4,2,1-thiadiazolo-(3,5')-4,5-dihydro-2-phenylpyridazin-e], 3'-Ethoxycarbonyl-6-methyl-1'-(p-Fluorophenyl)spiro[1' H-4,2,1-thiadiazolo-(3,5')-4,5-dihydro-2-phenylpyrida-zine], 3'-Ethoxycarbonyl-6-methyl-1'-(p-Nitrophenyl)spiro[1' H-4,2,1-thiadiazolo-(3,5')-4,5-dihydro-2-phenylpyrida-zine], 3'-Ethoxycarbonyl-6-methyl-1'-(p-Methylphenyl)spiro[1' H-4,2,1-thiadiazolo-(3,5')-4,5-dihydro-2-phénylpyridaz-ine], 400 ATC microculture plate reader, DMSO