Synthesis and anti-HIV activity evaluation of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo-[4,5-e][1,2]thiadiazines

Arch Pharm (Weinheim). 2008 Apr;341(4):216-22. doi: 10.1002/ardp.200700216.

Abstract

A series of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo[4,5-e] [1,2,4]thiadiazines (PTDs) was synthesized, structurally confirmed by spectral analysis, and evaluated for their anti-HIV activities by inhibition of HIV-induced cytopathogenicity in MT-4 cell culture. The results showed that some compounds exhibited inhibitory activity specifically against HIV-2 replication. The most active HIV-2 inhibitor was compound 7i (R1 = benzyl, R2 = 4-t-butyl-benzyl) with an EC50 value of 18.7 microM and SI=15, which may provide a useful lead for further molecular optimization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology
  • Cell Line
  • Cyclic S-Oxides / chemical synthesis*
  • Cyclic S-Oxides / pharmacology
  • Cytopathogenic Effect, Viral / drug effects
  • Drug Design
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • HIV-2 / drug effects
  • HIV-2 / physiology
  • Humans
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship
  • Thiadiazines / chemical synthesis*
  • Thiadiazines / pharmacology
  • Virus Replication / drug effects

Substances

  • 2-benzyl-4-(4-(t-butyl)chlorobenzyl)-7-methyl-1,1,3-trioxo-2,4-dihydropyrazolo(4,5-e)(1,4)thiadiazine
  • Anti-HIV Agents
  • Cyclic S-Oxides
  • Pyrazoles
  • Thiadiazines