NOVEL COMPOUND AS KCNQ POTASSIUM CHANNEL AGONIST, PREPARATION METHOD THEREFOR AND USE THEREOF

摘要

The present invention provides compounds having the structure represented by general formula I, pharmaceutically acceptable salts thereofagonist, preparation methods therefor and a use thereof in the preparation of a medicine for the treatment of nervous system diseases. The compounds or pharmaceutical compositions thereof can be used as the KCNQ potassium channel agonist for treating nervous system diseases. Compared to retigabine, a compound in the prior art, the compound of the present invention have the same or better therapeutic effect, are easier for synthesis and storage, and less prone to oxidate deterioration.;

主权项

1. A compound of the following general formula I or a pharmaceutically acceptable salt thereof: wherein, L is not present, or L is a linking radical selected from the group consisting ofoptionally substituted by C1-C4 alkyl;
R1 is a radical selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C1-C6 alkylamino carbonyl, C2-C8 alkenyl, C5-C7 cycloalkenyl, C2-C8 alkynyl and C6-C10 aryl; wherein, the C1-C6 alkyl is unsubstituted or optionally substituted by hydroxyl, amino, C1-C4 alkoxyl, alkylcarbonyl, halogen atom, C6-C10 aryl or halogenated C6-C10 aryl; the C2-C8 alkenyl is unsubstituted or optionally substituted by hydroxyl, amino, C1-C4 alkylcarbonyl, C1-C4 alkoxyl, halogen atom, C6-C10 aryl or halogenated C6-C10 aryl; and the C2-C8 alkynyl is unsubstituted or optionally substituted by hydroxyl, amino, C1-C4 alkylcarbonyl, alkoxyl, halogen atom, C6-C10 aryl or halogenated C6-C10 aryl; R2 is a radical selected from the group consisting of halogen atom and C1-C4 alkoxyl; R3 is a radical selected from the group consisting of H, halogen atom, trifluoromethyl, cyano, nitro, C1-C4 alkylcarbonyl and C1-C4 alkoxycarbonyl; X is O, S or NH; Y is not present, or Y is O or NR7, wherein R7 is a radical selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and C3-C8 cycloalkyl; R4 is a radical selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and C6-C10 aryl; R5 is a radical selected from the group consisting of H, halogen atom, amino, C1-C6 alkylamino andor R5, together with adjacentforms a fused-ring structure of R6 is H, C1-C6 alkyl or C3-C6 cycloalkyl; and in the above said definitions of substituents, the halogen atom or the halogen atom in halogenated group is F, Cl or Br.