Certain kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof

摘要

Disclosed herein are 2-,4-,6-substituted pyrimidine compounds of formula I, wherein: · X and Y are N; · R1 is optionally substituted phenyl with 1-3 groups independently selected from halo, alkyl groups having 1 to 4 carbon atoms, trifluoromethyl, alkoxy groups having 1 to 4 carbon atoms, and hydroxyl; · L is chosen from -C(O)O-, -C(O)N(R3)-, -N(R3)C(O)-, and -S(O)2N(R3)-; · R2 is hydrogen; · R3 is chosen from hydrogen and lower alkyl; · R4 is chosen from hydrogen and optionally substituted lower alkyl; and · R5 is hydrogen, · provided that the compound of Formula I is not 6-pheny Ipyrimidine-4-carboxylic acid; 6-(4-fluorophenyl)-pyrimidine-4-carboxylic acid; methyl 6-phenylpyrimidine-4-carboxylate; ethyl 6-phenylpyrimidine-4-carboxylate; or 6-phenylpyrimidine-4-carboxamide processes for their preparation, compositions comprising said compounds and uses thereof. Said compounds are useful as kynurenine-3-monooxygenase inhibitors and are therefore useful in the treatment of 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.