HECT E3 ligase inhibitors and uses thereof

A compound of general formula (I):

• wherein:
• Z is CH2 or CO;
• R1 is hydrogen or C1-C6 alkyl;
• R2 is COOR4, CO—R5, CN or CONR6R7;
• R3 is H or OH;
• n is an integer from 1 to 3;
• m is 1 or 2;
• W is aryl or heteroaryl;
• A-B is CH2—CH2, O—CH2, CH2—O, NR8-CO or CO—NR8;
• X, X′, Y are each independently selected from the group consisting of:
• hydrogen, C1-C6 alkyl, OH, NH2, C1-C6-alkoxy, C1-C6-alkylamino, C1-C6-dialkylamino, CONR6R7, halogen, CF3, NO2 and CN, said C1-C6 alkyl or C1-C6 alkoxy being optionally substituted with a substituent selected from the group consisting of:
• R9, OH, NH2, C1-C6-alkoxy, (C1-C6-alkoxy)C1-C6-alkoxy, C2-C6-alkynyloxy, C2-C6-alkynyl, C1-C6-alkylamino, C1-C6-dialkylamino, aryl and heteroaryl;
• R4 is hydrogen or C1-C6 alkyl, said C1-C6 alkyl being optionally substituted with a substituent selected from the group consisting of:
• R9, C2-C6-alkynyl, C1-C6-alkoxy, C2-C6-alkynyloxy and (C1-C6-alkoxy)C1-C6-alkoxy;
• R5 is C3-6 cycloalkyl, C1-C6 alkyl, aryl, heteroaryl,
• said C1-C6 alkyl being optionally substituted by aryl or heteroaryl;
• R6, R7 are each independently selected from the group consisting of:
• hydrogen, aryl, C1-C6 alkyl, C1-C6-alkoxy, O-aryl and O-heterocycloalkyl, said C1-C6 alkyl, C1-C6-alkoxy, O-aryl or O-heterocycloalkyl being optionally substituted with a substituent selected from the group consisting of:
• OH, NH2, C1-C6-alkoxy, C1-C6-alkylamino, C1-C6-dialkylamino, aryl, heteroaryl and C2-C6-alkynyl;
• R8 is hydrogen or C1-C6 alkyl, said C1-C6 alkyl being optionally substituted with a substituent selected from the group consisting of:
• OH, NH2, C1-C6-alkoxy, C1-C6-alkylamino, C1-C6-dialkylamino, aryl, heteroaryl, (C1-C6-alkoxy)C1-C6-alkoxy, [(C1-C6-alkoxy)C1-C6-alkoxy]C1-C6-alkoxy and C2-C6-alkynyloxy;
• R9 is k or
• k is an integer from 1 to 10;
• or a stereoisomer, solvate, tautomer or pharmaceutically acceptable salt thereof.