Synthesis and biological evaluation of pyrazole-fused oleanolic acid derivatives as novel inhibitors of inflammatory and osteoclast differentiation

Bioorg Med Chem. 2023 Feb 15:80:117177. doi: 10.1016/j.bmc.2023.117177. Epub 2023 Jan 20.


A series of pyrazole-fused oleanolic acid derivatives were designed and synthesized. The modification of these analogues focused on the substituents screening on the pyrazole ring. The cytotoxicity of these compounds and their anti-inflammatory activities via inhibiting interleukin-1β (IL-1β) production were evaluated in RAW264.7 cells. Most of the derivatives showed significantly improved potency compared with oleanolic acid. Among them, compound 7n exhibited the most potent anti-inflammatory activity on decreasing IL-1β production with low cytotoxicity. Moreover, the further study found 7n could inhibit RANKL-induced osteoclast differentiation on bone marrow-derived macrophages (BMMs). These findings may provide a potential direction for the drug development of osteoarthritis.

Keywords: Anti-inflammatory; Antiosteoclastic activity; IL-1β inhibition; Oleanolic acid derivatives; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Macrophages
  • Oleanolic Acid*
  • Osteoclasts*
  • Pyrazoles / pharmacology
  • RANK Ligand / pharmacology


  • Oleanolic Acid
  • Pyrazoles
  • RANK Ligand