Indole Amide Derivatives and Related Compounds for Use in the Treatment of Neurodegenerative Diseases

A compound of formula (BB1) or a stereoisomer, enantiomer or tautomer thereof,

• wherein,
• each dotted line individually represents an optional double bond, wherein maximally two dotted lines selected from the five dotted lines are a double bond;
• E1 is independently selected from CR1;
• and N;
• E2 is independently selected from NR2;
• and O;
• E3 is independently selected from CR3;
• and N;
• Ra is hydrogen or can be taken together with Rb to form a substituted or unsubstituted 4, 5, 6, 7 or 8 membered ring containing one N atom, preferably a piperidine ring;
• Rb is hydrogen or can be taken together with Ra to form a substituted or unsubstituted 4, 5, 6, 7 or 8 membered ring containing one N atom, preferably a piperidine ring;
• Q is independently selected from NRb—C(O);
• C(O);
• and C(O)NH;
• each R1, R3, R4, and R6 is independently selected from hydrogen;
• halogen;
• —OH;
• —OR10;
• —SH;
• —SR10;
• —S(O)R11;
• —S(O)2R11;
• —SO2NR12R13;
• trifluoromethyl;
• trifluoromethoxy;
• nitro;
• —NHC(O)R10;
• —NHS(O)2R10;
• —NHC(O)NR12R13;
• —NR10C(O)R10;
• —NR10S(O)2R10;
• —NR10C(O)NR12R13;
• —NR12R13;
• -cyano;
• —COOH;
• —COOR10;
• —C(O)NR12R13;
• —C(O)R11;
• alkyl;
• alkenyl;
• alkynyl;
• aryl;
• heterocycle;
• arylalkylene;
• arylalkenylene;
• arylalkynylene;
• heterocycle-alkylene;
• heterocycle-alkenylene;
• heterocycle-alkynylene;
• and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene, optionally includes one or more heteroatoms in the alkyl(ene), alkenyl(ene) or alkynyl(ene) moiety, said heteroatoms being selected from the atoms O, S and N;
• and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene can be unsubstituted or substituted with Z;
• and wherein a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene, can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
• R5 is selected from halogen;
• —OH;
• —SH;
• —SR10;
• —S(O)R11;
• —S(O)2R11;
• —SO2NR12R13;
• trifluoromethyl;
• trifluoromethoxy;
• nitro;
• —NHC(O)R10;
• —NHS(O)2R10;
• —NHC(O)NR12R13;
• —NR10C(O)R10;
• —NR10S(O)2R10;
• —NR10C(O)NR12R13;
• —NR12R13;
• -cyano;
• —COOH;
• —COOR10;
• —C(O)NR12R13;
• —C(O)R11;
• alkyl;
• alkenyl;
• alkynyl;
• aryl;
• heterocycle;
• arylalkylene;
• arylalkenylene;
• arylalkynylene;
• heterocycle-alkylene;
• heterocycle-alkenylene;
• heterocycle-alkynylene;
• and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene, optionally includes one or more heteroatoms in the alkyl(ene), alkenyl(ene) or alkynyl(ene) moiety, said heteroatoms being selected from the atoms O, S and N;
• and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene can be unsubstituted or substituted with Z;
• and wherein a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene, can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;-
• R2 is selected from hydrogen;
• alkyl;
• alkenyl;
• and alkynyl;
• n is selected from 0;
• 1 or 2;
• each of X, Y, T, W and V is independently selected from —CZ1H—;
• —CZ1—;
• —C—;
• —N—;
• NR101;
• —O—;
• —S—;
• or —CO—;
• wherein at least one of X, Y, T;
• W or V is selected from —CZ1H— or —CZ1— or —Cl—;
• L is independently selected from being not present;
• —O—;
• —NH—;
• —NR10—;
• C1-6alkylene;
• C1-6alkenylene;
• C1-6alkynylene;
• wherein each of said C1-6alkylene, C1-6alkenylene or C1-6alkynylene optionally includes one or more heteroatoms, said heteroatoms being selected from the heteroatoms consisting of O, S and N, and wherein each of said C1-6alkylene, C1-6alkenylene or C1-6alkynylene, can be unsubstituted or substituted;
• and wherein a carbon atom or heteroatom of said C1-6alkylene, C1-6alkenylene or C1-6alkynylene, can be oxidized to form a C═S, N═O, N═S, S═O or S(O)2;
• B represents a cyclic structure selected from cycloalkyl;
• cycloalkenyl;
• cycloalkynyl;
• aryl;
• and heterocycle;
• m is selected from 0;
• 1;
• 2;
• 3;
• 4 and 5;
• R8 is independently selected from hydrogen;
• halogen;
• alkyl;
• alkenyl;
• alkynyl;
• —OH;
• —OR10;
• —SH;
• —SR10;
• —S(O)R11;
• —S(O)2R11;
• —SO2NR12R13;
• trifluoromethyl;
• trifluoromethoxy;
• nitro;
• —NHC(O)R10;
• —NHS(O)2R10;
• —NHC(O)NR12R13;
• —NR10C(O)R10;
• —NR10S(O)2R10;
• —NR10C(O)NR12R13;
• —NR12R13;
• -cyano;
• —COOH;
• —COOR10;
• —C(O)NR12R13;
• —C(O)R11;
• wherein said alkyl, alkenyl and alkynyl optionally includes one or more heteroatoms, said heteroatoms being selected from the atoms O, S and N;
• and wherein said alkyl, alkenyl and alkynyl can be unsubstituted or substituted with Z;
• and wherein a carbon atom or heteroatom of said alkyl, alkenyl and alkynyl, can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
• each Z is independently selected from halogen;
• —OH;
• —OR10;
• —SH;
• —SR10;
• —S(O)R11;
• —S(O)2R11;
• —SO2NR13;
• trifluoromethoxy;
• nitro;
• —NHC(O)R10;
• —NHS(O)2R10;
• —NHC(O)NR12R13;
• —NR10C(O)R10;
• —NR10S(O)2R10;
• —NR10C(O)NR12R13;
• —NR12R13;
• -cyano;
• —COOH;
• —COOR10;
• —C(O)NR12R13;
• —C(O)R11;
• each Z1 is independently selected from hydrogen;
• alkyl;
• and Z;
• each R10 is independently selected from alkyl;
• alkenyl;
• alkynyl;
• aryl;
• heterocycle;
• arylalkylene;
• arylalkenylene;
• arylalkynylene;
• heterocycle-alkylene;
• heterocycle-alkenylene or heterocycle-alkynylene;
• and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene optionally include one or more heteroatoms in the alkyl(ene), alkenyl(ene) or alkynyl(ene) moiety, said heteroatom selected from O, S and N;
• and wherein a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene, can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
• each R101 is independently selected from hydrogen and R10;
• each R11 is independently selected from hydroxyl;
• alkyl;
• alkenyl;
• alkynyl;
• aryl;
• heterocycle;
• arylalkylene;
• arylalkenylene;
• arylalkynylene;
• heterocycle-alkylene;
• heterocycle-alkenylene or heterocycle-alkynylene;
• and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene optionally include one or more heteroatoms in the alkyl(ene), alkenyl(ene) or alkynyl(ene) moiety, said heteroatom selected from O, S and N;
• and wherein a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene, can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
• each R12 and R13 is independently selected from hydrogen;
• alkyl;
• alkenyl;
• alkynyl;
• aryl;
• heterocycle;
• arylalkylene;
• arylalkenylene;
• arylalkynylene;
• heterocycle-alkylene;
• heterocycle-alkenylene or heterocycle-alkynylene;
• and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene optionally include one or more heteroatoms in the alkyl(ene), alkenyl(ene) or alkynyl(ene) moiety, said heteroatom selected from O, S and N;
• and wherein a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene, can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
• and wherein R12 and R13 can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted;
• and stereoisomers, enantiomers or tautomers, solvates, hydrates, or salts (in particular pharmaceutically acceptable salts) thereof.

A compound of formula (CC 1) or a stereoisomer, enantiomer or tautomer thereof,

• wherein,
• each dotted line individually represents an optional double bond, wherein maximally two dotted lines selected from the five dotted lines are a double bond;
• each of G1, G2, G3 and G4 is independently selected from N;
• NRc3;
• O;
• CHRc3;
• and CRc3;
• wherein two of G1, G2, G3 and G4 are selected from N;
• NRc3;
• and O;
• while the other two of G1, G2, G3 and G4 are selected from CHRc3;
• and CRc3;
• each R3 is selected from hydrogen;
• and alkyl;
• R5 is independently selected from halogen;
• —OH;
• —OR10;
• —SH;
• —SR10;
• —S(O)R11;
• —S(O)2R11;
• —SO2NR12R13;
• trifluoromethyl;
• trifluoromethoxy;
• nitro;
• —NHC(O)R10;
• —NHS(O)2R10;
• —NHC(O)NR12R13;
• —NR10C(O)R10;
• —NR10S(O)2R10;
• —NR10C(O)NR12R13;
• —NR12R13;
• -cyano;
• —COOH;
• —COOR10;
• —C(O)NR12R13;
• —C(O)R11;
• alkyl;
• alkenyl;
• alkynyl;
• aryl;
• heterocycle;
• arylalkylene;
• arylalkenylene;
• arylalkynylene;
• heterocycle-alkylene;
• heterocycle-alkenylene;
• heterocycle-alkynylene;
• and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene, optionally includes one or more heteroatoms in the alkyl(ene), alkenyl(ene) or alkynyl(ene) moiety, said heteroatoms being selected from the atoms O, S and N;
• and wherein a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene, can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
• q is selected from 0;
• 1;
• 2;
• or 3;
• preferably q is 0 or 1;
• E is selected from hydrogen;
• halogen;
• —OH;
• —OR10;
• —SH;
• —SR10;
• trifluoromethoxy;
• —NHC(O)R10;
• —NHS(O)2R10;
• —NHC(O)NR12R13;
• —NR10C(O)R10;
• —NR10S(O)2R10;
• —NR10C(O)NR12R13;
• —NR12R13;
• each R10 is independently selected from alkyl;
• alkenyl;
• alkynyl;
• aryl;
• heterocycle;
• arylalkylene;
• arylalkenylene;
• arylalkynylene;
• heterocycle-alkylene;
• heterocycle-alkenylene or heterocycle-alkynylene;
• and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene optionally include one or more heteroatoms in the alkyl(ene), alkenyl(ene) or alkynyl(ene) moiety, said heteroatom selected from O, S and N;
• and wherein a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene, can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
• each R12 and R13 is independently selected from hydrogen;
• alkyl;
• alkenyl;
• alkynyl;
• aryl;
• heterocycle;
• arylalkylene;
• arylalkenylene;
• arylalkynylene;
• heterocycle-alkylene;
• heterocycle-alkenylene or heterocycle-alkynylene;
• and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene optionally include one or more heteroatoms in the alkyl(ene), alkenyl(ene) or alkynyl(ene) moiety, said heteroatom selected from O, S and N;
• and wherein a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkylene, arylalkenylene, arylalkynylene, heterocycle-alkylene, heterocycle-alkenylene or heterocycle-alkynylene, can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
• and wherein R12 and R13 can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted;
• each of R1c and R2c is independently selected from hydrogen;
• halogen;
• alkyl;
• alkenyl or alkynyl;
• and stereoisomers, enantiomers or tautomers, solvates, hydrates, or salts (in particular pharmaceutically acceptable salts) thereof.