Original Article

SYNTHESIS OF 2-[5,6-DIPHENYL-3(2H)-PYRIDAZINONE-2-YL]ACETAMIDE AND 3-[5,6-DIPHENYL-3(2H)-PYRIDAZINONE-2-YL]PROPANAMIDE DERIVATIVES AS ANALGESIC AND ANTI-INFLAMMATORY AGENTS

  • Deniz S. DOGRUER
  • Serdar ÜNLÜ
  • Esra KÜPELI
  • Erden BANOGLU
  • M. Fethi SAHIN

Received Date: 01.12.2006 Accepted Date: 20.03.2007 Turk J Pharm Sci 2007;4(2):57-70

Abstract In this study, new sixteen 2-[5,6-diphenyl-3(2H)-pyridazinone-2-yl] acetamide and 3-[5,6- diphenyl-3(2H)-pyridazinone-2-yl] propanamide derivatives were synthesized and their in vivo analgesic and anti-inflammatory activities were tested in mice. Propanamide derivatives were found more potent than acetamide derivatives in terms of anti-inflammatory activity. The compound 8e which is a propanamide derivative exhibited higher analgesic and anti-inflammatory activities than other synthesized compounds and did not cause any gastric lesions and bleeding in stomachs of tested animals. Inhibitory activity of the active compounds on cyclooxygenase isoforms was also investigated by using in vitro human “whole blood assay” and found that these derivatives did not exert their analgesic and anti-inflammatory activities through COX inhibition and other mechanisms might be involved. Özet Bu çalismada, onalti yeni 2-[5,6-difenil-3(2H)-piridazinon-2-il] asetamit ve 3-[5,6-difenil- 3(2H)-piridazinon-2-il] propanamit türevleri sentez edilmis ve bunlarin analjezik ve antienflamatuvar etkileri fareler üzerinde test edilmistir.Propanamit türevleri antienflamatuvar etki bakimindan asetamit türevlerinden daha güçlü bulunmustur. Propanamit türevi olan bilesik 8e sentezi yapilan diger bilesikler ile karsilastirildiginda daha yüksek analjezik ve antienflamatuvar etki göstermis ve test edilen hayvanlarda gastrik lezyon veya kanamaya neden olmamistir. Aktif bilesiklerin siklooksijenaz izoformlari üzerine inhibitör etkileri “in vitro insan tam kan” yöntemiyle arastirilmis ve bu bilesiklerin analjezik ve antienflamatuvar etkilerini COX inhibibisyonu araciligiyla göstermedikleri, baska mekanizmalarin etkili olabilecegi bildirilmistir.

Keywords: 5,6-Diphenyl-3(2H)-pyridazinone, analgesic and anti-inflammatory activity, cyclooxygenase inhibition