Antiinflammatory 4,5-diarylpyrroles: synthesis and QSAR

J Med Chem. 1994 Apr 1;37(7):988-98. doi: 10.1021/jm00033a017.

Abstract

A series of 2-substituted- and 2,3-disubstituted-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-1H- pyrroles was synthesized and found to be active in the rat adjuvant arthritis model of inflammation. The most active compounds were the 2-halo derivatives in the order of chloro > bromo > iodo. The same pattern of activity was observed for the 2,3-dihalopyrroles. Quantitative structure-activity relationship studies suggested that the activity could be correlated with the molar refractivity and the inductive field effect of the 2-substituent and the lipophilicity of the 3-substituent.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Arthritis, Experimental / drug therapy
  • Disease Models, Animal
  • Drug Tolerance
  • Male
  • Pyrroles / chemical synthesis*
  • Pyrroles / pharmacokinetics
  • Pyrroles / therapeutic use
  • Pyrroles / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Pyrroles