Variously substituted 2-mercaptobenzenesulfonamides (A) and 3-aroyl-1,1-dioxo-1,4,2-
benzodithiaznes (B) were synthesized in our laboratories and described as a novel class of potent HIV-1 integrase inhibitors [1,2]. Recently, we have found that the compound of type C (R¹ = Me, R² = H) showed also remarkable anti-HIV activity with 50% effective concentration EC₅₀ value of 0.94 μM and no significant cytotoxicity at 200.0 μM [3].
The above findings prompted us to develop new methodologies for the syntheses of the compounds depicted as D and E. The syntheses of the target compounds were achieved by convenient three or four step procedures starting from the corresponding 4-chloro-3-methylthio-1,4,2-benzodithiazine 1,1-dioxides.

The in vitro anti-HIV activity of compounds 14, 22-25, 27, 30 and 31 has been tested at the NCI (Bethesda, USA). The selected compound with remarkable anti-HIV activity (EC₅₀ = 0.09μM) and very high therapeutic index (TI=1177.7) was 9-chloro - 2,3,4 - trihydro - 7 - methyl - 6,6 - dioxopyrimido[1,2-b][1,4,2]benzodithiazine (25).

References:
1. Kuo Ch.L., Assefa H., Kamath S., Brzozowski Z., Sławiński J., Sączewski F., Buolamwini J.K., Neamati N., J. Med. Chem., 2004, 47, 385-399.
2. Brzozowski Z., Sączewski F., Sanchez T., Kuo Ch.L., Gdaniec M., Neamati N., Bioorg. Med. Chem., 2004, 12, 3663-3672.
3. Brzozowski Z., Sączewski F., Neamati N., Bioorg Med. Chem., 2006, in press.

This study was supported by Polish State Committee for Scientific Research (grant no 2 P05 035 27).

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/6438 must be provided.

1. Synthesis, structure and biological activity of 1-[(imidazolidin-2-yl)imino]azoles*
2. 2-(4,5-DIHYDROIMIDAZOL-2-YL)BENZIMIDAZOLES AS SELECTIVE IMIDAZOLINE I₂ / ADRENERGIC A₂ RECEPTOR LIGANDS
3. SYNTHESIS AND APPLICATION OF 2-IMINOIMIDAZOLIDINES TO THE SYNTHESIS OF NOVEL FUSED HETEROCYCLIC RING SYSTEMS*
4. SYNTHESIS, CRYSTAL STRUCTURE AND BIOLOGICAL ACTIVITY OF COPPER (II) COMPLEXES WITH CHELATING BIDENTATE 2-SUBSTITUTED BENZIMIDAZOLE LIGANDS.