Selective and Reversible Inhibitors of Ubiquitin Specific Protease 7

A compound of formula (I′):

• wherein
• R1, each identical or different, is chosen from the group consisting of halogen, R, OR, CN, CF3, C(O)R, C(O)OR, C(O)NRR′, NO2, (C1-C6)alkylene-OR, (C1-C6)alkylene-NRR′, (C1-C6)alkylene-CO2R, (C1-C6)alkylene-CONRR′, —O—(C1-C6)alkylene-CO2R, —O—(C1-C6)alkylene-CONRR′, CO2—(C1-C6)alkylene-OR, CO2—(C1-C6)alkylene-NRR′, C(O)NH—(C1-C6)alkylene-OR, CONH—(C1-C6)alkylene-NRR′, OCF3, SO2R, SO3H, SO2NRR′, NHSO2R, R10C≡CR11, (R10)(R11)C═C(R11)2, (C1-C6)alkylene-COR, NHCOR, or (C1-C6)alkyl interrupted by at least one heteroatom, preferably chosen among O, N or S, preferably O;
• L1 is linear or branched (C1-C6)alkylene optionally substituted by one or more of ═O, CN, C(O)R, C(O)OR, or C(O)NRR′, or linear or branched CH2(C1-C6)alkylene, wherein the later (C1-C6)alkylene is optionally substituted by one or more of halogen, OR, NRR′ or CF3;
• q is 0, 1, 2, 3 or 4
• X′ is CR7;
• R7 is OR, halogen, linear or branched (C1-C6)alkyl-OR, C(O)OR, C(O)NRR′, CN, OR9, NRR′ or SR;
• n is 0, 1 or 2;
• p is 1, 2 or 3;
• R3, R4, R8′ and R8, each identical or different, are chosen in the group consisting of H, linear or branched (C1-C6)alkyl, halogen, OH, —O—(C1-C6)alkyl, NRR, CN, CF3, OR, C(O)R, C(O)OR or C(O)NRR′;
• A is chosen from the group consisting of:
• —C(O)—;
• —C(O)NH—;
• SO2—;
• or
• SO2N—;
• L2 is linear or branched (C1-C6)alkylene optionally interrupted by at least one heteroatom chosen from O, NR or S and/or optionally substituted by:
• R, OR, NRR′, (C1-C6)alkyl-OR, (C1-C6)alkyl-NRR′, OC(O)R, NHC(O)R, NHC(O)NRR′, CN, C(═NH)NHOR;
• R6 is chosen from the group consisting in aryl, heteroaryl, cycloalkyl, heterocycle, H, wherein the aryl, heteroaryl, cycloalkyl or heterocycle is mono or polycyclic and is optionally substituted by one or more of linear or branched (C1-C6)alkyl, halogen, NRR, CN, CF3, OR, ═O, C(O)R, C(O)OR, NHC(O)R, OC(O)R, linear or branched (C2-C6)alkenylene or C(O)NRR′;
• each R and R′, identical or different, are independently chosen from H, linear or branched (C1-C6)alkyl, cycloalkyl, aryl, aromatic or non aromatic heterocycle, linear or branched —(C1-C6)alkyl-aryl or linear or branched —(C1-C6)alkyl-heterocycle, wherein the heterocycle is aromatic or non aromatic;
• optionally substituted or not by OH, CO2H, C(O)NH2, NH2
• R9 is chosen from the group consisting of C(O)R, —C(O)NHR, —C(O)OR, —C(O)CH2—NRR′, —C(O)—CH2—CH2—CO2R, —C(O)—CH2—SO3H, —C(O)—(C5H4N), —PO3H2, or their ionized form;
• R10 independently is chosen from a bond, a linear or branched (C1-C6)alkyl;
• R11 independently is chosen from an hydrogen atom, a linear or branched (C1-C6)alkyl or an aryl, the alkyl or aryl is optionally substituted by OH, NH2, C(O)OH or C(O)NH;
• or their pharmaceutically acceptable salts or their optical isomers, racemates, diastereoisomers, enantiomers or tautomers,
• with the exception of
• q is 0, L1 is CH2, X′ is CR7 and R7 is OH, i is 1, A is C═O, L2 is C2H4 and R6 is
• q is 1, R1 is Cl at position 7, L1 is CH2, X′ is CR7 and R7 is OH, i is 1, A is C═O, L2R6 is CH(CH2CH3)2.