Design and evaluation of pyrazolopyrimidines as KCNQ channel modulators

Bioorg Med Chem Lett. 2019 Oct 1;29(19):126603. doi: 10.1016/j.bmcl.2019.08.007. Epub 2019 Aug 6.


Effective treatments of neuropathic pain have been a focus of many discovery programs. KCNQ (kv7) are voltage gated potassium channel openers that have the potential for the treatment of CNS disorders including neuropathic pain. Clinical studies have suggested agents such as Retigabine to be a modulator of pain-like effects such as hyperalgesia and allodynia. In this paper, we describe the discovery and evaluation of a series of novel pyrazolopyrimidines and their affinity for potassium channels KCNQ2/3. These pyrazolopyrimidines have also shown good efficacy in the capsaicin-induced acute and secondary mechanical allodynia model and excellent pharmacokinetic properties, which may be superior to Retigabine.

Keywords: KCNQ; Kv7; Potassium channel.

Publication types

  • Evaluation Study

MeSH terms

  • Drug Design*
  • Humans
  • Hyperalgesia / drug therapy*
  • Ion Channel Gating / drug effects*
  • KCNQ Potassium Channels / antagonists & inhibitors*
  • Potassium Channel Blockers / chemistry*
  • Potassium Channel Blockers / pharmacology*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*


  • KCNQ Potassium Channels
  • Potassium Channel Blockers
  • Pyrazoles
  • Pyrimidines