Synthesis and evaluation of the analgesic and anti-inflammatory activity of new 3(2H)-pyridazinone derivatives

Arzneimittelforschung. 2004;54(7):396-401. doi: 10.1055/s-0031-1296990.

Abstract

A series of 6-substituted-3(2H)-pyridazinone derivatives were synthesized and evaluated for analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR, 1H-NMR spectra and elementary analysis. Analgesic and anti-inflammatory activities of the title compounds have been evaluated. Four of the ten tested compounds possessed significant analgesic effects in the phenylbenzoquinone-induced writhing test (PBQ test). The most active derivatives 8a, 8b, 8d, 8e were void of gastric ulcerogenic effect or acute toxicity at the maximal dose (200 mg/kg p.o.). In the carrageenan-induced paw edema model, compound 8d (6- [4- (2-fluorophenyl) piperazin-1-yl]-3(2H)-pyridazinone) showed anti-inflammatory activity similar to that of the standard drug indometacin (CAS 53-86-1). A significant dependence of the anti-inflammatory effect on the substituents was observed; The pharmacological study of these compounds confirms that modification of the chemical group at position 6 of the 3(2H)-pyridazinone ring influences analgesic and anti-inflammatory activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Non-Narcotic / chemical synthesis*
  • Analgesics, Non-Narcotic / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Biological Assay
  • Carrageenan
  • Chemical Phenomena
  • Chemistry, Physical
  • Dose-Response Relationship, Drug
  • Edema / chemically induced
  • Edema / prevention & control
  • Indicators and Reagents
  • Male
  • Mice
  • Pain Measurement / drug effects
  • Pyridazines / chemical synthesis*
  • Pyridazines / pharmacology*
  • Stomach Ulcer / chemically induced

Substances

  • Analgesics, Non-Narcotic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Indicators and Reagents
  • Pyridazines
  • Carrageenan