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

摘要

Certain chemical entities 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. 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.

主权项

1. At least one chemical entity chosen from compounds of Formula I and pharmaceutically acceptable salts thereof wherein: R1 is chosen from optionally substituted aryl and optionally substituted heteroaryl; R2 is tetrazolyl; R3 is chosen from hydrogen and optionally substituted lower alkyl and R4 is chosen from hydrogen, halo, optionally substituted lower alkyl, hydroxyl, optionally substituted lower alkoxy, and optionally substituted amino, or R1 and R4, taken together with intervening atoms form a bicyclic ring of the formula which is optionally substituted where m is 0 or 1 and n is 0 or 1, provided that at least one of m and n is 1, provided that
1) when R3 and R4 are hydrogen, then R1 is not 5-chloropyridin-3-yl, 3,5-dichlorophenyl, orwhere R21 is halo and R22 is hydrogen, halo, trifluoromethoxy, methyl, or isopropoxy.