( S)- N-[1-(4-Cyclopropylmethyl-3,4-dihydro-2 H-benzo [1,4]oxazin-6-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide is a potent and efficacious KCNQ2 opener which inhibits induced hyperexcitability of rat hippocampal neurons

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 8; pp. 1991 - 1995
• Main Authors: Wu, Yong-Jin, Boissard, Christopher G, Chen, Jie, Fitzpatrick, William, Gao, Qi, Gribkoff, Valentin K, Harden, David G, He, Huan, Knox, Ronald J, Natale, Joanne, Pieschl, Rick L, Starrett, John E, Sun, Li-Qiang, Thompson, Mark, Weaver, David, Wu, Dedong, Dworetzky, Steven I
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 19.04.2004; Elsevier
• Subjects: Acrylamides - chemical synthesis; Acrylamides - pharmacology; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Dose-Response Relationship, Drug; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Humans; KCNQ2 Potassium Channel; Kidney - cytology; Kidney - drug effects; Kidney - metabolism; Medical sciences; Mice; Molecular Structure; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuropharmacology; Oxazines - chemical synthesis; Oxazines - pharmacology; Patch-Clamp Techniques; Pharmacology. Drug treatments; Potassium Channels - drug effects; Potassium Channels - genetics; Potassium Channels - metabolism; Potassium Channels, Voltage-Gated; Rats; Structure-Activity Relationship; Enantioselectivity; Rat; Rodentia; Central nervous system; Potassium channel agonist; Encephalon; Vertebrata; Mammalia; Neuron; Animal; Vinylic compound; Hyperexcitability; Bicyclic compound; Carboxamide; S configuration; Aromatic compound; Fluorine Organic compounds; Inhibition; Chemical synthesis; Oxygen nitrogen heterocycle
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.01.069

( S)- N-[1-(4-Cyclopropylmethyl-3,4-dihydro-2 H-benzo[1,4]oxazin-6-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide (( S)- 2) was identified as a potent and efficacious KCNQ2 opener. This compound demonstrated significant activity in reducing neuronal hyperexcitability in rat hippocampal slices, and the inhibition mediated by ( S)- 2 was reversed by the KCNQ blocker linopirdine. ( S)- N-[1-(4-Cyclopropylmethyl-3,4-dihydro-2 H-benzo[1,4]oxazin-6-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide (( S)- 2) was identified as a potent and efficacious KCNQ2 opener. This compound demonstrated significant activity in reducing neuronal hyperexcitability in rat hippocampal slices, and the inhibition mediated by ( S)- 2 was reversed by the KCNQ blocker linopirdine.