Valproic acid analogues and pharmaceutical composition thereof
OwnerFrank Abbott, Stoyan Karagiozovinventors
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Abstract
Analogues of valproic acid useful in treating neuroaffective disorders including convulsions, bipolar disorder, and migraine headache are disclosed. The analogues are halide liver substituted analogues, cyclic analogues, and conjugated diene analogues of valproic acid. Pharmaceutical compositions or prodrugs containing the analogues or pharmaceutically acceptable salts thereof are disclosed. Methods of malting the compounds and treating mammals with neuroaffective disorders are also disclosed.
Claims44
A compound selected from the group consisting of compounds represented by the formula (I) and stereoisomers and pharmaceutically acceptable salts thereof
- wherein said compound is an analogue of valproic acid and comprises between 5 and 13 carbon atoms;
- wherein X═C;
- wherein R1 is optionally present and when present is either H or F;
- wherein, when R1 is present, R2 and R3 are selected from the group consisting of a linear or branched C1 to C6 alkyl, a linear or branched C2 to C6 n-ene hydrocarbyl (where n=1-5), a linear or branched C1 to C6 n-yne hydrocarbyl (where n=1-5), a linear or branched C1 to C5 ether, a linear or branched C1 to C6 ketone, and —CHx-A where A=cyclic C3 to C8 hydrocarbyl and x=0-3;
- wherein, when R1 is H, at least one of R2 and R3 are selectively fluorinated;
- wherein, when R1 is F, R2 and R3 comprise linear or branched alkenyl groups;
- wherein, when R1 is not present, R2 is H, there is a double bond between R3 and X, and R3 is
- wherein n is 1 to 10;
- or when R1 is not present, there is a single bond between X and R2, R2 is
- wherein R4, R5 and R6 are selected from the group consisting of H, methyl, ethyl, F, NH2, cyclopropyl, CF3, and saturated or unsaturated cyclic (C3 to C8) hydrocarbyl, there is a double bond between R3 and X, and R3 is
- wherein R7 and R8 are selected from the group consisting of H, methyl, ethyl, F, NH2, cyclopropyl and CF3, and R9, R10, and R11 are selected from the group consisting of H, methyl, ethyl, F, NH2, cyclopropyl and CF3.
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A method of synthesizing an analogue of valproic acid comprising the steps set forth in any one of Schemes 4, 5, 6, 7, 8, 9, and 10.
Dependencies are inferred from the claim text.