Synthesis and evaluation of 2-(2,6-dihalophenyl)-3-pyrimidinyl-1,3-thiazolidin-4-one analogues as anti-HIV-1 agents

Bioorg Med Chem. 2007 May 1;15(9):3134-42. doi: 10.1016/j.bmc.2007.02.044. Epub 2007 Feb 23.


A series of 2-(2,6-dihalophenyl)-3-(substituted pyrimidinyl)-1,3-thiazolidin-4-ones were designed on the prediction of quantitative structure-activity relationship (QSAR) studies, synthesized, and evaluated as HIV-1 reverse transcriptase inhibitors. Our attempts in correlating the identified molecular surface features related properties for modeling the HIV-1 RT inhibitory activity resulted in some statistically significant QSAR models with good predictive ability. The results showed that compounds 4m and 4n were highly active in inhibiting HIV-1 replication with EC(50) values in the range of 22-28 nM in MT-4 as well as in CEM cells with selectivity indexes of >10,000. The derived models collectively suggest that the compounds should be compact without bulky substitution on its peripheries for better HIV-1 RT inhibitory activity. These models also indicate a preference for hydrophobic compounds to obtain good HIV-1 RT inhibitory activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Cell Line, Tumor
  • Drug Design
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects
  • HIV-2 / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Quantitative Structure-Activity Relationship
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Stereoisomerism
  • Thiazolidines / chemical synthesis*
  • Thiazolidines / chemistry
  • Thiazolidines / pharmacology*


  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Thiazolidines
  • HIV Reverse Transcriptase