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US 10,766,886 B2Granted
Retinoic acid receptor antagonists as chaperone-mediated autophagy modulators and uses thereof
AssigneeAlbert Einstein College of Medicine
InventorsAna Maria Cuervo, Evripidis Gavathiotis, Qisheng Xin, Bhaskar C. Das
Life of this patent
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Abstract
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.
Claims11
A compound of formula (II), wherein formula (II) is
- wherein
- R1, 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, heterocycloalkyl, 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, heteroaroaralkyl, 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;
- and
- X is N;
- and Y is N;
- or a pharmaceutically acceptable salt thereof.
7 more elements
A compound of formula (II), wherein formula (II) is
- or a pharmaceutically acceptable salt thereof, wherein
- R1, 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, heterocycloalkyl, 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, heteroaroaralkyl, 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);
- and
- R10 and R11 are independently H or C1-C6 alkyl.
4 more elements
A compound of the formula
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is Cl,
- R2, R3, R4, R5, R6, R8, and R9 are H, and
- R7 is NHCOCH3.
1 more element
A compound of the formula
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is Cl,
- R2, R3, R4, R5, R6, R8, and R9 are H, and
- R7 is phenyl.
1 more element
Dependencies are inferred from the claim text.