The sulfonamides constitute an important class of therapeutic agents in current medicinal science and various structurally novel sulfonamide derivatives have recently been reported to show substantial anti-HIV activities. Our extensive research program is aimed at the synthesis of 1,1-dioxo-3-methylthio-1,4,2-benzodithiazines and their subsequent transformation into 4-chloro-2-mercaptobenzenesulfonamides with the nitrogen atom of sulfonamide moiety attached to variety of heterocyclic ring systems. These compounds, depending on structure, displayed either anticancer [1,5] or anti-HIV activities [2,5] and have been described by Neamati as a novel class of potent HIV-1 integrase inhibitors [3,4]. These findings have increased our interest on new anti-HIV agents and led us to synthetize variously substituted 4-chloro-2-mercapto-N-(1-alkyl-1,4,5,6-tetrahydro-1,2,4-triazin-3-yl)benzenesulfonamides. The reactions of substrates 1 a-g with the appropriate (2-aminoethyl)alkylhydrazine carried
out in methanol afforded title compounds 2-16.

The compounds tested for their in vitro anti-HIV activity in the US National Cancer Institute were essentially inactive, while 4-chloro-2-mercapto-N-(1-metyl-1,4,5,6-tetrahydro
-1,2,4-triazin-3-yl)benzenesulfonamide displayed significant activity (IC50 = 158 μM, EC50 = 25.4 μM, TI50 = 6.21).

References:
1. E. Pomarnacka, M. Gdaniec, Bioorg. Med. Chem. 11 (2003) 1259-1267.
2. E. Pomarnacka, Acta Polon. Pharm. Drug Res. 55 (1998) 481-486.
3. N. Neamati, A. Mazumder, J.M. Owen, R.J. Schultz, S. Sunder, Y. Pommier, Antiviral Chem. Chemotherapy 8 (1997) 485-495.
4. L. C. Kuo, H. Assefa, Z. Brzozowski, J. Sławiński, F. Sączewski, J.K. Buolamwini, N. Nemati, J. Med. Chem. 47 (2004) 385-399.
5. E. Pomarnacka, A. Kornicka, Farmaco 56 (2001) 571-577.

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1. Syntheses of N,S-substituted 4-chloro-2-mercapto-5-methylbenzenesulfonamide derivatives with potential biological activity