3-pyrrolidine-indole derivatives as serotonergic psychedelic agents for the treatment of CNS disorders

A compound of Formula (I) or a pharmaceutically acceptable salt and/or solvate thereof:

• R1 is selected from hydrogen, C1-C3alkyl, C1-C6alkyleneP(O)(OR9)2, C(O)R9, CO2R9, C(O)N(R9)2, S(O)R9 and SO2R9;
• R2, R3 and R4 are independently selected from hydrogen and C1-C6alkyl;
• R5 is selected from hydrogen and C1-C6alkyl;
• R6, R7 and R8 are independently selected from hydrogen, halogen, CN, OR9, N(R9)2, SR9, C1-C6alkyl, C1-C6haloalkyl, C2-C6haloalkenyl, CO2R9, C(O)N(R9)2, S(O)R9, SO2R9, C2-C6alkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3-C7cycloalkyl and a 3- to 7-membered heterocyclic ring including 1 to 2 ring heteromoeities selected from O, S, S(O), SO2, N and NR9, wherein said C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3-C7cycloalkyl and 3- to 7-membered heterocyclic ring groups are optionally substituted by one or more substituents independently selected from CN, OR9, N(R9)2 and SR9, and wherein said C3-C7cycloalkyl and 3- to 7-membered heterocyclic ring are each further optionally substituted with a substituent selected from halogen, CO2R9, C(O)N(R9)2, SO2R9, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3-C6cycloalkyl and a 3- to 6-membered heterocyclic ring including 1 to 2 ring heteromoeities selected from O, S, S(O), SO2, N, and NR9,
• Y is selected from halogen and Q-A;
• Q is selected from O, NR10, S, S(O) and SO2;
• wherein each R9 and R10 are independently selected from hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C2-C6alkynyl, substituted or unsubstituted C1-C6haloalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted C3-C7heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted C1-C6alkyleneC3-C7cycloalkyl, substituted or unsubstituted C1-C6alkyleneC3-C7heterocycloalkyl, substituted or unsubstituted C1-C6alkylenearyl, and substituted or unsubstituted C1-C6alkyleneheteroaryl;
• and
• A is selected from hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, C4-C6cycloalkenyl, heterocycloalkyl, aryl, heteroaryl, P(O)(OR11)2, C1-C6alkyleneP(O)(OR11)2, C1-C6alkyleneC3-C7cycloalkyl, C1-C6alkyleneC4-C6cycloalkenyl, C1-C6alkyleneheterocycloalkyl, C1-C6alkylenearyl, C1-C6alkyleneheteroaryl, C(O)Q′, C(O)2(Q′), C(O)N(Q′)2, SO(Q′) and SO2(Q′);
• wherein Q′ is selected from hydrogen, C1-C20alkyl, C1-C20haloalkyl, C2-C20alkenyl, C2-C20haloalkenyl, C2-C20alkynyl, C2-C20haloalkynyl, C3-C7cycloalkyl, and a 3- to 7-membered heterocyclic ring including 1 to 2 ring heteromoeities selected from the group consisting of O, S, S(O), SO2, N, and NR10, wherein said C1-C20alkyl, C2-C20haloalkyl, C2-C6alkenyl, C2-C20haloalkenyl, C3-C7cycloalkyl, and 3- to 7-membered heterocyclic ring groups are optionally substituted by one or more substituents independently selected from CN, OR10, N(R10)2, and SR10, and/or are disubstituted on the same carbon atom with C1-C6alkyl, or with C2-6alkylene to form a C3-C7cycloalkyl ring, and wherein said C3-C7cycloalkyl and 3- to 7-membered heterocyclic ring are each further optionally substituted with a member of the group consisting of C1-C3alkyl and C1-C3haloalkyl;
• and
• each R11 is independently selected from hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C2-C6alkynyl, substituted or unsubstituted C1-C6haloalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted C1-C6alkyleneC3-C7cycloalkyl, substituted or unsubstituted C1-C6alkyleneC3-C7heterocycloalkyl, substituted or unsubstituted C1-C6alkylenearyl, and substituted or unsubstituted C1-C6alkyleneheteroaryl;
• wherein all available hydrogen atoms are optionally substituted with a halogen atom and/or all available atoms are optionally substituted with an alternate isotope thereof,
• provided
• when A is CH3, Q is O, R1 is H or CH3 and R2, R3, R4 and R5 are all hydrogen, then R6, R7 and/or R8 are not OCH3;
• when A is CH3 and Q is O, then R1 to R8 are not all hydrogen;
• and
• when A is hydrogen, Q is O and one of R1, R2 and R5 is methyl and the other two of R1, R2 and R5 are both hydrogen, then R3, R4 and R6 to R8 are not all hydrogen.