Investigations of new pyridazinone derivatives for the synthesis of potent analgesic and anti-inflammatory compounds with cyclooxygenase inhibitory activity

Okcelik B., Unlu S., BANOĞLU E., Kupeli E., Yesilada E., Sahin M.

ARCHIV DER PHARMAZIE, cilt.336, sa.9, ss.406-412, 2003 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 336 Sayı: 9
  • Basım Tarihi: 2003
  • Doi Numarası: 10.1002/ardp.200300778
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.406-412
  • Anahtar Kelimeler: 2-oxo-3H-benzoxazole, pyridazinone, analgesic, anti-inflammatory, COX-1, COX-2, ANTINOCICEPTIVE ACTIVITY, COX-2 INHIBITORS, AMIDE DERIVATIVES, SELECTIVITY, DRUGS
  • Gazi Üniversitesi Adresli: Evet

Özet

In this study we describe the synthesis of two novel 4-phenyl- and 4-(2-chlorophenyl)-6-(5-chloro-2-oxo-3H-benzoxazol-7-yl)-3(2H)-pyridazinone derivatives (compounds 8 a and b) and their testing as inhibitors of cyclooxygenases (COX-1 and COX-2). Both compounds inhibited COX-1 (by 59 % and 61 % for compounds 8 a and 8 b respectively) and COX-2 (by 37 % and 28 % for compounds 8 a and 8 b respectively) at a concentration of 10 muM. Furthermore, we tested the analgesic and anti-inflammatory activities of the synthesized compounds in vivo by using the p-benzoquinone-induced writhing test and the carrageenan-induced hind paw edema model, respectively. Compounds 8 a and b showed potent analgesic and anti-inflammatory activities without causing gastric lesions in the tested animals.