Discovery of (S,E)-3-(2-fluorophenyl)-N-(1-(3-(pyridin-3-yloxy)phenyl)ethyl)-acrylamide as a potent and efficacious KCNQ2 (Kv7.2) opener for the treatment of neuropathic pain

Yong-Jin Wu; Charles M Conway; Li-Qiang Sun; Frederic Machet; Jie Chen; Ping Chen; Huan He; Clotilde Bourin; Vincenzo Calandra; Joseph L Polino; Carl D Davis; Karen Heman; Valentin K Gribkoff; Christopher G Boissard; Ronald J Knox; Mark W Thompson; William Fitzpatrick; David Weaver; David G Harden; Joanne Natale; Steven I Dworetzky; John E Starrett Jr

doi:10.1016/j.bmcl.2013.08.092

Discovery of (S,E)-3-(2-fluorophenyl)-N-(1-(3-(pyridin-3-yloxy)phenyl)ethyl)-acrylamide as a potent and efficacious KCNQ2 (Kv7.2) opener for the treatment of neuropathic pain

Bioorg Med Chem Lett. 2013 Nov 15;23(22):6188-91. doi: 10.1016/j.bmcl.2013.08.092. Epub 2013 Sep 8.

Affiliation

¹ Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA. Electronic address: yong-jin.wu@bms.com.

PMID: 24070783
DOI: 10.1016/j.bmcl.2013.08.092

Abstract

Acrylamide (S)-6, a potent and efficacious KCNQ2 (Kv7.2) opener, demonstrated significant activity in two models of neuropathic pain and in the formalin test, suggesting that KCNQ2 openers may be useful in the treatment of neuropathic pain including diabetic neuropathy.

Keywords: Acrylamide; Diabetic neuropathy; KCNQ2; Kv7.2; Neuropathic pain.

MeSH terms

Acrylamides / chemical synthesis
Acrylamides / chemistry*
Acrylamides / pharmacology*
Animals
KCNQ2 Potassium Channel / chemistry
KCNQ2 Potassium Channel / metabolism*
Male
Neuralgia / drug therapy*
Patch-Clamp Techniques
Rats
Rats, Sprague-Dawley

Substances

Acrylamides
KCNQ2 Potassium Channel