N-Benzyl-2-chloroindole-3-carboxylic acids as potential anti-inflammatory agents. Synthesis and screening for the effects on human neutrophil functions and on COX1/COX2 activity

Eur J Med Chem. 2004 Sep;39(9):785-91. doi: 10.1016/j.ejmech.2004.06.008.

Abstract

The synthesis of N-benzyl-2-chloroindole-3-carboxylic acids related to indomethacin is reported. These compounds were tested on in vitro human neutrophil activation. Some of them, more soluble in water, were tested to define the influence on prostaglandin biosynthesis via inhibition of cyclooxygenases (COX1 and COX2) by a chemiluminescent method suitable for fast screening. Several derivatives showed inhibitory effects and in some cases were more active than the parent compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / pharmacology*
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Drug Design
  • Drug Evaluation, Preclinical / methods
  • Enzyme Activation / drug effects
  • Humans
  • Indoles / chemistry*
  • Membrane Proteins
  • Molecular Structure
  • Neutrophils / drug effects*
  • Neutrophils / physiology
  • Prostaglandin-Endoperoxide Synthases / physiology
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Carboxylic Acids
  • Indoles
  • Membrane Proteins
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases