Synthesis and cyclooxygenase inhibitory activities of some N-acylhydrazone derivatives of isoxazolo[4,5-d]pyridazin-4(5H)-ones


UENSAL-TAN O., Oezden K., Rauk A., BALKAN A.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.45, no.6, pp.2345-2352, 2010 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 45 Issue: 6
  • Publication Date: 2010
  • Doi Number: 10.1016/j.ejmech.2010.02.012
  • Journal Name: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.2345-2352
  • Keywords: Cyclooxygenase enzymes, Isoxazolo[4,5-d]pyridazin-4(5H)-one, N-Acylhydrazone, Docking, PHARMACOLOGICAL EVALUATION, ANALGESIC ACTIVITY, MASS-SPECTRA, ISOMERIZATION, ACID

Abstract

In this study, new isoxazolo[4,5-d]pyridazin-4(5H)-one derivatives having an N-acylhydrazone moiety were synthesized. The compounds were tested for their COX inhibitory activities using NS-398 and indomethacine as reference compounds. Although the compounds had an inhibitory profile against both COX-1 and COX-2, most were found to be more selective against COX-2 by a small percentage of inhibition, at the concentration of 50 mu M. Docking studies were clone to understand the interactions of the tested compounds with the active site of COX-2. It was observed that the compounds fit into, and interacted with, the hydrophobic parts which are common in the active pocket of COX-1 and COX-2 enzymes but could not fit to the area which is specific for COX-2 enzyme.