US 6,855,829 B2 · 3-fluoro-2-oxindole modulators of KCNQ potassium channels and use thereof in treating migraine and mechanistically related disease

Abstract

Compounds which function as modulators, particularly, openers, of human KCNQ potassium channel proteins or polypeptides, particularly, central nervous system (CNS)-located KCNQ potassium channels, and heteromultimers thereof, and their use in the treatment of migraine are provided by the present invention. One novel type of potassium channel polypeptide openers provided by the present invention is the fluorooxindole compounds, described for the first time as therapeutics for the treatment of migraine by preventing the asynchronous firing of neurons. Other KCNQ potassium channel opener compounds that are also useful in the treatments of the invention include 2,4-disubstituted pyrimidine-5-carboxamide derivatives. One or more of the compounds according to the present invention may be utilized alone, in combination, or in conjunction with other treatment modalities for reducing, ameliorating and/or alleviating migraine or diseases similar to, or mechanistically related to, migraine, e.g., cluster headache.

Claims8

Dependent claims

An opener or activator compound which modulates the biological activity of central nervous system-associated KCNQ potassium channel polypeptides by hyperpolarizing neurons that fire before or during a migraine headache or migraine-related disorder, the opener or activator compound comprising a compound according to Formula I and pharmaceutically acceptable salts thereof, Formula I having the structure

wherein
R1, R2, R3 and R4 are each independently hydrogen, C1-4 alkyl halogen, fluoromethyl, trifluoromethyl, phenyl, 4-methylphenyl or 4-trifluromethylphenyl;
R5 is C16 alkyl, optionally substituted with one to three same or different groups selected from fluoro and chloro, provided that R5 is not C1-6 alkyl when Y is O;
Y is O or S;
and
R6 and R7 are each independently hydrogen, chloro, bromo or trifluoromethyl.

3 more elements

Dependencies are inferred from the claim text.

3-fluoro-2-oxindole modulators of KCNQ potassium channels and use thereof in treating migraine and mechanistically related disease

Life of this patent

3-fluoro-2-oxindole modulators of KCNQ potassium channels and use thereof in treating migraine and mechanistically related disease

Life of this patent

Abstract

Claims8