Pyrazolopyridazine alpha-2-delta-1 ligands for the treatment of neuropathic pain

James W Myatt, Mark P Healy, Gianpaolo S Bravi, Andrew Billinton, Christopher N Johnson, Kim L Matthews, Karamjit S Jandu, Wenjing Meng, Anne Hersey, David G Livermore, Clement B Douault, Jason Witherington, Rino A Bit, James E Rowedder, Jason D Brown, Nick M Clayton

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Optimization of the novel alpha-2-delta-1 ligand 4 provided compounds 37 and 38 which have improved DMPK profiles, good in vivo analgesic activity and in vitro selectivity over alpha-2-delta-2. An in-house P-gp prediction programme and the MetaSite software package were used to help solve the specific problems of high P-gp efflux and high in vivo clearance.
Original languageEnglish
Pages (from-to)4683-8
Number of pages6
JournalBioorganic & Medicinal Chemistry Letters
Volume20
Issue number15
DOIs
Publication statusPublished - 1 Aug 2010

Keywords

  • Analgesics
  • Animals
  • Calcium Channel Blockers
  • Calcium Channels
  • Ligands
  • Neuralgia
  • P-Glycoprotein
  • Pyrazoles
  • Pyridazines
  • Pyridines
  • Rats
  • Structure-Activity Relationship

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