Synthesis, ex vivo and in vitro hydrolysis study of an indoline derivative designed as an anti-inflammatory with reduced gastric ulceration properties

Molecules. 2009 Aug 26;14(9):3187-97. doi: 10.3390/molecules14093187.

Abstract

The compound 1-(2,6-dichlorophenyl)indolin-2-one (1), planned as a pro-drug of diclofenac (2), was easily synthesized in 94% yield by an intramolecular reaction in the presence of coupling agent (i.e., EDC). Compound 1 showed anti-inflammatory and analgesic activity without gastro-ulcerogenic effects. The chemical and enzymatic hydrolysis profile of the lactam derivative 1 does not indicate conversion to diclofenac (2). This compound is a new non-ulcerogenic prototype for treatment of chronic inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects*
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Carrageenan
  • Celecoxib
  • Diclofenac / adverse effects
  • Diclofenac / chemistry
  • Diclofenac / pharmacology
  • Drug Design*
  • Hydrolysis / drug effects
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Lactams / blood
  • Lactams / chemistry
  • Male
  • Models, Molecular
  • Pyrazoles / adverse effects
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Wistar
  • Stomach Ulcer / chemically induced*
  • Sulfonamides / adverse effects
  • Sulfonamides / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Indoles
  • Lactams
  • Pyrazoles
  • Sulfonamides
  • Diclofenac
  • Carrageenan
  • Celecoxib