Synthesis, ex Vivo and in Vitro Hydrolysis Study of an Indoline Derivative Designed as an Anti-Inflammatory with Reduced Gastric Ulceration Properties

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.

Keywords

• indolinone
• pro-drug
• anti-inflammatory
• hydrolysis
• diclofenac