| 摘要 |
601547 Certain heterocycle substituted pyrimidine derivatives are provided herein. Also provided are pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, olivoponto cerebellar atrophy, non-Alzheimer’s dementia, multi-infarctual dementia, cerebral amyotrophic lateral sclerosis, cerebral ischemia, cerebral hypoxia, spinal or head trauma and epilepsy. Also described are methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity Compounds of the disclosure include: 3-[6-(3-Chloro-4-trifluoromethoxy-phenyl)-pyrimidin-4-yl]-4 H-[1,2,4]oxadiazol-5-one, 4-(3,4-difluorophenyl)-6-(1H-tetrazol-5-yl)-pyrimidine, 4-[6-(3,4-Dichloro-phenyl)-pyrimidin-4-yl]-piperazin-2-one, 4-(3-Chloro-phenyl)-6-pyrazol-1-yl-pyrimidine, 4-(3-Chloro-phenyI)-6-imidazoI-1-yl-pyrimidine, 4-(3,4-Dichloro-phenyl)-6-[1,2,4]triazol-1-yI-pyrimidine, 6-[6-(3,4-Dichloro-phenyl)-pyrimidin-4-yI]-N -methyI-nicotinamide, 4-(3,4-Dichloro-phenyl)-2-methyl-6-(4-methyl-oxazol-2-yl)-pyrimidine, 2-[6-(3-Chloro-phenyl)-pyrimidin-4-yI]-5 ,6-difluoro-1H-benzoimidazole, and 2-[6-(3-Chloro-phenyl)-pyrimidin-4-yI]-benzooxazole. |
