| 摘要 |
The present invention relates to methods of treating neurodegenerative diseases comprising administering, to a subject in need of such treatment, one or more agent that inhibits or reduces the action, including the catalytic activity, of an enzyme of the phospholipase D family, such as phospholipase D1 and/or phospholipase D2. The present invention also relates to cell-based assays which may be used to identify agents that inhibit or reduce the activity of enzymes of the phospholipase D family and that may be used in the treatment of neurodegenerative diseases. |
| 主权项 |
1. A method of treating a neurodegenerative disease selected from the group consisting of Alzheimer's disease, Mild Cognitive Impairment, Parkinson's Disease, Huntington's disease and senile dementia, comprising administering to a subject in need of such treatment, an effective amount of an inhibitor of phospholipase D2, wherein the inhibitor is selected from the group consisting of
i) inhibitors depicted in (FIG. 11B-M); (ii) a halopemide derivative comprising a 2-indolyl moiety, a halogenated piperidinylbenzimidazolone moiety and an S-methyl moiety, or a 1,3,8-triazaspiro[4,5]decan-4-one moiety; (iii) 5-Fluoro-2-indolyl des-chlorohalopemide (“FIPI”); (iv) N-(2-(4-(2˜oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)ethyl)-2-napthamide; (v) (1R,2R)—N—((S)-1-(4-(5-bromo-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propan-2-yl)-2-phenylcyclopropanecarboxamide; (vi) N-(2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]decan-8-yl)ethyl)quinoline-3-carboxamide; and (vii) an inhibitor selected from the group consisting of |
