An integrated overview on pyrrolizines as potential anti-inflammatory, analgesic and antipyretic agents

Eur J Med Chem. 2016 May 23:114:257-92. doi: 10.1016/j.ejmech.2016.01.055. Epub 2016 Feb 1.

Abstract

Despite the existence of huge number of NSAIDs, the quest for safer drugs is still in the focus of several drug discovery programs. Pyrrolizine heterocyclic system is among the privileged scaffolds utilized in this regard. At least one of these pyrrolizines, ketorolac, has reached the market. The current review represents a collective effort to highlight the reported pyrrolizines with anti-inflammatory and analgesic potential and categorize them into eight different classes. Furthermore, the various synthetic approaches, structure-activity relationship as well as metabolic pathways have been discussed. Taken together, this review sets a base for researchers to design and synthesize novel pyrrolizine-based libraries for further development into safer and efficient anti-inflammatory and analgesic agents.

Keywords: Anti-inflammatory; COX/5-LOX dual inhibitors; Ketorolac; Licofelone; NSAIDs; Pyrrolizine; SFZ-47.

Publication types

  • Review

MeSH terms

  • Analgesics / chemistry
  • Analgesics / metabolism
  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / metabolism
  • Cyclooxygenase Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Pyrroles / chemistry
  • Pyrroles / metabolism
  • Pyrroles / pharmacology*
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Prostaglandin / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Pyrroles
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Prostaglandin-Endoperoxide Synthases
  • prostaglandin D2 receptor