2. Academic Validation
  3. Design and evaluation of pyrazolopyrimidines as KCNQ channel modulators

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.
Augustine T Osuma 1,  Xiangdong Xu 2,  Zhi Wang 2,  Jennifer A Van Camp 2,  Gail M Freiberg 2
Affiliations

Affiliations

  • 1 Discovery, AbbVie Inc., North Chicago, IL 60064-6101, United States. Electronic address: augustine.osuma@abbvie.com.
  • 2 Discovery, AbbVie Inc., North Chicago, IL 60064-6101, United States.
PMID: 31416667 DOI: 10.1016/j.bmcl.2019.08.007
Abstract

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.

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