Synthesis and Biological Evaluation of New Diarylpyrazole and Triarylimidazoline Derivatives as Selective COX-2 Inhibitors

Arch Pharm (Weinheim). 2017 Aug;350(8). doi: 10.1002/ardp.201600386. Epub 2017 Jun 12.

Abstract

New series of diarylpyrazoles 8a-f and triarylimidazoline-5-ones 11a-g were synthesized and evaluated for their in vitro cyclooxygenase-1 (COX-1) and COX-2 inhibitory activity and in vivo anti-inflammatory activity. The synthesized compounds showed good selectivity for COX-2; compounds 8a, 8d, 8f, 11a, and 11c exhibited the highest COX-2 selectivity indexes (SI = 4.77-5.43) compared to the reference drug celecoxib (SI = 7.8). All compounds showed good in vivo anti-inflammatory activity, especially compounds 8a, 8f, 11c, and 11d, which also showed some similarities to the time interval pattern of celecoxib at all different time intervals (1, 3, and 6 h).

Keywords: Anti-inflammatory; Imidazoline; Pyrazole; Selective COX-2 inhibitor.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Celecoxib / pharmacology
  • Cyclooxygenase 1 / drug effects
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cyclooxygenase Inhibitors / chemical synthesis
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology
  • Humans
  • Imidazolines / chemical synthesis
  • Imidazolines / chemistry
  • Imidazolines / pharmacology*
  • Male
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Wistar
  • Sheep
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Imidazolines
  • Pyrazoles
  • Cyclooxygenase 1
  • Celecoxib