RETINOIC ACID RECEPTOR ANTAGONISTS AS CHAPERONE-MEDIATED AUTOPHAGY MODULATORS AND USES THEREOF

摘要

Compounds, compositions and methods are provided for selectively activating chaperone-mediated autophagy (CMA), protecting cells from oxidative stress, proteotoxicity and lipotoxicity, and/or antagonizing activity of retinoic acid receptor alpha (RARα) in subjects in need thereof.

主权项

1. A compound having the structure of formula (I) wherein R1 and R2 of formula (I) are independently H or methyl; R4, R5, R6 and R7 of formula (I) are independently, H, hydroxyl, halogen or alkyl, or R8 and R5 or R6 of formula (I) together form a 5- or 6-membered heteroaryl; and R8 of formula (I) is C≡N, 5- or 6-membered heteroaryl,where a represents the point of attachment of R8 to the 6-membered ring and Q is a 5- or 6-membered heteroaryl or Q and C═O of R8 together form a 5- or 6-membered heteroaryl, or R8 and R5 or R6 of formula (I) together form a 5- or 6-membered heteroaryl, where each heteroaryl can be optionally substituted with one or more of CN, ═O, NH2 and phenyl;
or a pharmaceutically acceptable salt thereof.