Studies on 1,2,4-Benzothiadiazine 1,1-Dioxides VII and Quinazolinones IV: Synthesis of Novel Built-In Hydroxyguanidine Tricycles as Potential Anticancer Agents

Abstract

A b s t r a c t -Two representative built-in hydroxyguanidine tricycles containing 1.2.4-benzothiadiazine 1 , l -dioxides (3) and quinazolinones @) were prepared by reductive cyclization of 1-(2-nitrophenylsulfonyl)-2-benzylthio-2-imidazoline ( 1-(2-nitrophenylsulfonyl)-2-benzylthio-1,4,5,6-tetrahydropyrimidine 1-(2-nitrobenzoyl).2-benzylthio-2-imidazolidine W and 1-(2-nitrobenz0yl)-2-benzylthio-l.4,5,6-tetrahydropyrimidinehydrobromide respectively with zinc dust in acetic acid under ice-cooling. 2.10-Dihydro-10-hydroxy-3H- imidazo[l,2-h][1,2,4[benzothiadiazine 55-dioxide ( and 2,3,4,11t e t r a h y d r o -I 1 -hydroxypyrimido[l,2-bl[1,2,4lbenzothiadiazine 6,6dioxide 0 were found to be active against solid tumor cell lines such as KB.Colo 205.HeLa.and Hepa-2.Hydroxyguanidine ( 1 ) .hydroxyurea (2) and their derivatives constitute a class of anticancer and antiviral agents3 It has been repwted that these agents inactivate ribonucleotide reductase which is an essential enzyme for the DNA synthesis and cell replication and is considered as an important target for the