Non-acidic pyrazole EP1 receptor antagonists with in vivo analgesic efficacy

Bioorg Med Chem Lett. 2008 Jun 1;18(11):3392-9. doi: 10.1016/j.bmcl.2008.04.018. Epub 2008 Apr 11.

Abstract

Replacement of the carboxylic acid group in a series of previously described methylene-linked pyrazole EP(1) receptor antagonists led to the discovery of amide, reversed amide and carbamate derivatives. Two compounds, 10a and 10b, were identified as brain penetrant compounds and both demonstrated efficacy in the CFA model of inflammatory pain.

MeSH terms

  • Analgesics / chemical synthesis*
  • Analgesics / chemistry
  • Analgesics / pharmacology*
  • Animals
  • Brain / drug effects
  • Central Nervous System / drug effects
  • Combinatorial Chemistry Techniques
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Molecular Structure
  • Pain Measurement
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Rats
  • Receptors, Prostaglandin E / antagonists & inhibitors*
  • Receptors, Prostaglandin E, EP1 Subtype
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Pyrazoles
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP1 Subtype