Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides

Bioorg Med Chem. 2004 Dec 1;12(23):6171-82. doi: 10.1016/j.bmc.2004.08.050.

Abstract

A random high-throughput screening (HTS) program to discover novel nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been carried out with MT-4 cells against a nevirapine-resistant virus, HIV-1(IIIB-R). The primary hit, a thiazolidenebenzenesulfonamide derivative, possessed good activity. A systematic modification program examining various substituents at the 3-, 4-, and 5-positions on the thiazole ring afforded compounds with enhanced anti-HIV-1 and reverse transcriptase (RT) inhibitory activities. These results confirm the important role of the substituents at these positions and the thiazolidenebenzenesulfonamide motif as a valuable lead series for the next generation NNRTIs.

MeSH terms

  • Benzenesulfonates
  • Binding Sites
  • Drug Resistance, Viral
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects
  • Molecular Structure
  • Nevirapine
  • Protein Binding
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / pharmacology
  • Thiazoles
  • Virus Replication / drug effects

Substances

  • Benzenesulfonates
  • Reverse Transcriptase Inhibitors
  • Sulfonamides
  • Thiazoles
  • Nevirapine
  • HIV Reverse Transcriptase