Pyrazol-3-propanoic acid derivatives as novel inhibitors of leukotriene biosynthesis in human neutrophils

ÇALIŞKAN B., Luderer S., Ozkan Y., Werz O., BANOĞLU E.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.46, sa.10, ss.5021-5033, 2011 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 46 Sayı: 10
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1016/j.ejmech.2011.08.009
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.5021-5033
  • Anahtar Kelimeler: Diarylpyrazole, 5-Lipoxygenase, Cyclooxygenase, Anti-leukotriene, 5-LIPOXYGENASE INHIBITOR, DUAL INHIBITION, CYCLOOXYGENASE-2, ZILEUTON, DISEASE, ACTIVATION, CANCER
  • Gazi Üniversitesi Adresli: Evet

Özet

We recently presented that compounds 4a-b moderately inhibited leukotriene (LT) formation in human neutrophils. For structural derivatization of 4a-b, novel thirty-six title compounds were synthesized and led to more potent inhibition of LT biosynthesis in activated human neutrophils exemplified by compounds 15, 27-30, 32-37, 41, 42 with IC50 values in the range of 1.6-3.5 mu M. Moreover, compounds 32,35,42,43 and 44 showed a substantial inhibition of platelet COX-1 activity with IC50 of 2.5, 0.041, 0.3, 0.9 and 0.014 mu M, respectively, leading up to dual acting inhibitors. On the basis of their high potency in cellular environment, these straightforward pyrazole-3-propanoic acid derivatives may possess potential in the design of more potent compounds for intervention with inflammatory and allergic diseases. (C) 2011 Elsevier Masson SAS. All rights reserved.