Antiinflammatory agents. 4. Syntheses and biological evaluation of potential prodrugs of 2-amino-3-benzoylbenzeneacetic acid and 2-amino-3-(4-chlorobenzoyl)benzeneacetic acid

J Med Chem. 1990 Aug;33(8):2296-304. doi: 10.1021/jm00170a039.

Abstract

A series of potential prodrugs of 2-amino-3-benzoylbenzeneacetic acid (amfenac) and 2-amino-3-(4-chlorobenzoyl)benzeneacetic acid were synthesized and evaluated for their cyclooxygenase inhibiting properties, antiinflammatory potency, and gastrointestinal irritation liability. One compound, 2-amino-3-(4-chlorobenzoyl)benzeneacetamide, possessed a therapeutic index 1 order of magnitude greater than that of indomethacin.

Publication types

  • Comparative Study

MeSH terms

  • Acetamides / chemical synthesis
  • Acetamides / therapeutic use
  • Acetamides / toxicity
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Arthritis, Experimental / drug therapy
  • Benzeneacetamides*
  • Carrageenan
  • Chemical Phenomena
  • Chemistry
  • Cyclooxygenase Inhibitors
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Indomethacin / therapeutic use
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Male
  • Molecular Structure
  • Phenylacetates / chemical synthesis*
  • Phenylacetates / therapeutic use
  • Phenylacetates / toxicity
  • Prodrugs / chemical synthesis*
  • Prodrugs / therapeutic use
  • Prodrugs / toxicity
  • Rats

Substances

  • Acetamides
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzeneacetamides
  • Cyclooxygenase Inhibitors
  • Phenylacetates
  • Prodrugs
  • amfenac
  • AHR 6293
  • AHR 10037
  • Carrageenan
  • Indomethacin