| 主权项 |
1. A method of selectively activating chaperone-mediated autophagy (CMA) in a subject in need thereof comprising administering to the subject a compound of formula (II), or a combination of any compounds thereof, in an amount effective to activate CMA,wherein the subject has Parkinson's Disease, Huntington's Disease, frontotemporal dementia, retinal degeneration, multiple sclerosis, diabetes, a lysosomal storage disorder, a retinal disease, a cardiovascular disease, myocardial infarction, cardiac hypertrophy or a cardiomyopathy, andwherein formula (II) iswhereinR1, R2, R3, R4, R5, R6, R8 and R9 of formula (II) are independently H, hydroxyl, halogen, SH, NO2, CF3, COOH, COOR10, CHO, CN, NH2, NHR10, NHCONH2, NHCONHR10, NHCOR10, NHSO2R10, OCR10, COR10, CH2R10, CON(R10,R11), CH═N—OR10, CH═NR10, OR10, SR10, SOR10, SO2R10, COOR10, CH2N(R10,R11), N(R10,R11), or optionally substituted lower alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalky, aryl, heteroaryl, aralkyl, or heteroaralkyl; wherein the optional substituent is one or more of F, Cl, Br, I, OH, SH, NO2, COOH, COOR10, R10, CHO, CN, NH2, NHR10, NHCONH2, NHCONHR10, NHCOR10, NHSO2R10, HOCR10, COR10, CH2R10, CON(R10, R11), CH═N—OR10, CH═NR10, OR10, SR10, SOR10, SO2R10, COOR10, CH2N(R10, R11), N(R10, R11);R7 of formula (II) is H, hydroxyl, halogen, CF3, CN, OCF3, COOH, COOCH3, COOR10, COO(CH2)2Si(CH3)3, COOR10Si(CH3)3, NHCOCH3, C≡C—CH2OH, C≡C—R10-OH or optionally substituted alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cyclic or heterocyclic; wherein the optional substituent is one or more of F, Cl, Br, I, OH, SH, NO2, CH3, R10, COOH, COOR10, CHO, CN, NH2, NHR10, NHCONH2, NHCONHR10, NHCOR10, NHSO2R10, HOCR10, COR10, CH2R10, CON(R10, R11), CH═N—OR10, CH═NR10, OR10, SR10, SOR10, SO2R10, COOR10, CH2N(R10, R11), N(R10, R11);R10 and R11 are independently H or C1-C6 alkyl; andX is O; and Y is N;or a pharmaceutically acceptable salt thereof. |
