Small molecules inducing the degradation of the cellular prion protein

A compound having general formula (I):

• wherein:
• ring B may be partially saturated, for instance a di-hydropyridinone ring when R1 is O and/or when one or both X is N, or insaturated, e.g. a pyridinone ring when R1 is O;
• R1 may be 0 or S;
• each atom on ring B may be independently a C or N atom;
• X may be independently selected from —C— or —O— or —N(R4)—, wherein R4 may be —H, or —C1-4 linear or cyclic alkyl;
• ring C is a 5- or 6-membered aromatic ring wherein each atom may be —C— or —N—, e.g. Y may independently be —C(R3) or —N(R3)— or —N═;
• R3 is selected from —H, C1-4 linear or cyclic alkyl group, alkoxyl or aryloxyl, ring A or Z-ring A;
• preferably, ring C has one or two heteroatoms;
• Z may be —CH2— or —O— or —N(H)— or —S(O2)— or —S(O)—;
• ring A may be an aromatic or heteroaromatic 5- or 6-membered ring, preferably a phenyl ring;
• ring A may be substituted at any position with one or more group R2 independently selected from:
• —H, —F, —Cl, —Br, —I, —CH3, —CH2CH3, —CH(CH3)2, —C(CH3)3, —CHF2, —CF3, —OH, —OCH3,
• —OCH2CH3, —OCF3, —OCH(CH3)2, —CN, —NO2, —NH2, —SH;
• or general formula (II):
• wherein:
• each atom on each ring may be independently a —C— or —N— atom;
• Z may be —H, —CH2—, —S(O2)—, —S(O)—, R1 may be absent (when Z is —H) or may be a group independently selected from:
• H, C1-4 linear, branched, cyclic alkyl or alkoxyl or aryloxyl optionally substituted with one or more of:
• —H, —F, —Cl,
• —Br, —I, —CH3, —CH2CH3, —CH(CH3)2, —C(CH3)3, —CHF2, —CF3,
• —OH, —OCH3, —OCH2CH3, —OCF3, —OCH(CH3)2, —CN, —NO2, —NH2, —S, a tetrahydrofuran ring or a tetrahydropyran ring wherein each atom of the ring may independently be substituted with —H or —OH, an aromatic or heteroaromatic 5- or 6-membered ring substituted at any position with one or more group R2 independently selected from:
• —H, —F, —Cl, —Br, —I, —CH3, —CH2CH3,
• —CH(CH3)2, —C(CH3)3, —CHF2, —CF3, —OH, —OCH3, —OCH2CH3,
• —OCF3, —OCH(CH3)2, —CN, —NO2, —NH2, —SH;
• ring A and ring B are each independently an aromatic or heteroaromatic 5- or 6-membered ring, preferably a phenyl ring;
• ring A and ring B may be independently substituted at any position with one or more group R2 independently selected from:
• —H, —F, —Cl, —Br, —I, —CH3, —CH2CH3, —CH(CH3)2, —C(CH3)3, —CHF2, —CF3, —OH, —OCH3,
• —OCH2CH3, —OCF3, —OCH(CH3)2, —CN, —NO2, —NH2, —SH;
• or general formula (III):
• wherein:
• each atom on each aromatic ring may be independently a C or N atom;
• ring B and ring C are fused imidazole rings,
• ring D is a pyrimidine ring, optionally ring D may be a cytosine or uracyl ring;
• R2 are each independently —H, —OH, —CH2OH, —CH3, —CH2CH3, halogen selected in the group comprising:
• —F, —Cl, —Br, —I, —CF3, —OCH3;
• X may be independently ═O, —NH2, ═S;
• R3 is independently selected from —H, C1-4 linear, branched or cyclic alkyl, ring A or Z-ring A;
• Z may be —CH2 or —S(O2)— or —S(O)—,
• ring A may be an aromatic or heteroaromatic 5- or 6-membered ring, preferably a phenyl ring;
• ring A may be substituted at any position with one or more group R1 independently selected from:
• —H, —F, —Cl, —Br, —I, —CH3, —CH2CH3, —CH(CH3)2, —C(CH3)3, —CHF2, —CF3, —OH, —OCH3,
• —OCH2CH3, —OCF3, —OCH(CH3)2, —CN, —NO2, —NH2, —SH;
• or general formula (IV):
• wherein:
• each atom on each ring may be independently a C or N atom;
• ring A and A′ are each independently an aromatic or heteroaromatic 5- or 6-membered ring, preferably a phenyl ring;
• ring A, A′ and B may be substituted at any position with one or more group R1 independently selected from:
• —H,
• —F, —Cl, —Br, —I, —CH3, —CH2CH3, —CH(CH3)2, —C(CH3)3,
• —CHF2, —CF3, —OH, —OCH3, —OCH2CH3, —OCF3, —OCH(CH3)2, —CN, —NO2, —NH2, —SH;
• ring B is an aromatic or a non aromatic ring wherein each atom may be independently one or more C or N or O or S or S(O2) atom and preferably is a piperidine ring;
• X is —CH2, —O—, —S—, —N(H), —C(O)—, —C(S)—, —C(H)═C(H)—, —S(O2), —S(O).