Use of compounds for the elevation of pyruvate dehydrogenase activity

摘要

Described is the use of compounds of formula (I) in the manufacture of a medicament for use in the elevation of pyruvate dehydrogenase (PDH) activity, wherein, C is optionally substituted phenyl or carbon-linked heteroaryl, and n is 1 or 2, and R1 is linked to ring C at a carbon ortho to the position of A-B attachment and is selected from C1-4 alkyl, halo-C1-4 alkyl, C1-4 alkoxy, halo-C1-4 alkoxy, C2-4 alkenyloxy, cyano, nitro, halo, trifluoromethylsulphanyl and hydroxy, or -X5-R81 wherein X5 is a direct bond, -O-, -S-, -SO2-, -OSO2O-, -NR82-, -CO-, -COO-, -OCO-, -CONR83-, -NR84CO-, -NR85COO-, -SO2NR86-, -NR87SO2-, -CH2-, -SO2NR88CO-, -OCONR89-, -CSNR90-, -NR91CS-, -NR92CSN93-, -NR94CONR100-, or R1 is -X6-R101 wherein X6 is a direct bond, -CO-, -O-, -OCH2-, -S-, -SO-, -SO2- or -NR102-, wherein R101 is optionally substituted phenyl, and R2 and R3 are independently hydrogen, halo, optionally substituted C1-3 alkyl, or together with the carbon atom to which they are attached, form an optionally substituted 3-5 membered cycloalkyl ring, and A-B is selected from -NHCO-, -OCH2-, -NHCH2-, trans-vinylene, ethynylene, -NHCS-, or -COCH2-, and R4 is hydroxy, hydrogen, halo, amino, or methyl.