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, cilt.45, ss.2345-2352, 2010 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 45 Konu: 6
  • Basım Tarihi: 2010
  • Doi Numarası: 10.1016/j.ejmech.2010.02.012
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Sayfa Sayıları: ss.2345-2352

Özet

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.