Synthesis Of N-acylsulfonamide And N’-acylsulfonylhydrazide Derivatives Of 4(3H)-quinazolinone

Recently, a large number of sulfonamides possessing antitumor activity, such as ABT-737 and Indisulam (E7070), have been reported. These compounds exhibited remarkable antitumor activity, interacting with different molecular targets. And some of them showed highly selectivity and specificity for targets, which are worthy of being lead compound for the research and development of antitumor agents. In our previous work, a variety of compounds containing 2-methyl-4-quinazolinone have been synthesized, some of them showed effective antitumor activity. In order to obtain more efficient antitumor agents and to examine the structure and activity relationship of this type of compounds, hereby 2 series of N-acylsulfonamide and N-acylsulfonylhydrazide derivatives containing the cycle 4(3H)-quinazolinone were designed and synthesized.Firstly, 2-methyl-4(3H)-quinazolinone was synthesized from 2-aminobenzoic acid via cyclization and amination, then chlorosulfonation and amination to give the intermediate 2-methyl-4(3H)-quinazolinone-6-sulfonamide. Consequently, the intermediate was converted into the first series of ten target compounds by the reaction with different benzoic acid.Secondly, the compounds of different benzohydrazide was synthesized from different benzoic acid, then interaction with 2-methyl-4(3H)-quinazolinone-6-sulfonyl chloride in the pyridine to give fourteen 2-methyl-4(3H)-quinazolinone-6-(N’-acyl) sulfonylhydrazides. Finally, the synthesis of 2-methyl-4(3H)-quinazolinone-6-sulfonyl chloride from 2-methyl-4(3H)-quinazolinone was also investigated.In summary, twenty four new sulfonamide compounds have been synthesized in this research, and their structures were confirmed by IR, MS and 1H-NMR. Although the antitumor activity of some target compounds was not ideal, it is benefit for our forward work.