Synthesis and Pharmacological Studies of Unprecedented Fused Pyridazino[3,4:5,6] [1,2,4] triazino[3,4-b][1,3,4]thiadiazine Derivatives

Abstract

A novel fused system with three or four fused rings—pyridazino[3,4:5,6][1,2,4] triazino[4,3-b][1,2,4,5]tetrazine and pyridazino[3,4:5,6][1,2,4]triazino[3,4-b]pyrimido[4,5-e][1,3,4] thiadiazine was obtained from the starting materials 4(6H)-amino-3-hydrazino-7-(2-thienyl) pyridazino[3,4-e][1,2,4]-triazine 2 and 9-amino-3-(2-thienyl)-2H,8H-pyridazino[3,4:5,6][1,2,4]triazino [1,3,4]thiadiazine-8-carbonitrile 12. Each of the starting compounds was subjected to a number of cyclization reactions to obtain a series of new heterocyclic fused systems, 3–10 and 13–23, via bifunctional reagents. Some of the synthesized compounds were screened against three cell lines including HepG2, HCT-116 and MCF-7 to discover their anticancer activity. The synthesized compounds were characterized depending on their elemental analyses and spectral data.