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US 2026/0092035 A1Published application
Indole derivatives as serotonergic agents useful for the treatment of disorders related thereto
AssigneeMindset Pharma Inc.
InventorAbdelmalik SLASSI
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to indole derivatives of general Formula (I), to processes for their preparation, to compositions including them and to their use in activation of a serotonin receptors in a cell, as well as to treating diseases, disorders, or conditions by activation of a serotonin receptors in a cell. The diseases, disorders, or conditions include, for example, psychosis, mental illnesses, and central nervous system (CNS) disorders.
Claims30
A compound of Formula (I)
- or a pharmaceutically acceptable salt, solvate, and/or prodrug thereof,
- wherein:
- X is O;
- R1 is H;
- R2 is selected from H, halo, and C1-C6alkyl;
- R3 is H;
- R4 is selected from H, CN, halo, C1-C6alkyl, C2-C6alkenyl, and C2-C6alkynyl;
- R5 is selected from H, CN, halo, C1-C6alkyl, C2-C6alkenyl, and C2-C6alkynyl;
- R6 is selected from H, C1-C10alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkenyleneZR14, C2-C6alkenyleneZR14, C2-C6alkynyleneZR14, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C1-C6alkenyleneC3-C7cycloalkyl, C1-C6alkenyleneC3-C10heterocycloalkyl, and C1-C6alkenyleneC5-C10heteroaryl, the latter five groups being optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OR15, and C(O)R15;
- R7 is selected from H, halo, and C1-C6alkyl;
- R8 is selected from H, halo, and C1-C6alkyl;
- R9 is selected from H and halo;
- R10 is selected from H and halo;
- R11 is selected from H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkenyleneZ′R16, C2-C6alkenyleneZ′R16, C2-C6alkynyleneZ′R16, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, C5-C10heteroaryl, C1-C6alkyleneC3-C7cycloalkyl, C1-C6alkenyleneC3-C10heterocycloalkyl, C1-C6alkyleneC6-C10aryl, and C1-C6alkyleneC5-C10heteroaryl, the latter eight groups being optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OR17, and C(O)R17;
- R12 is selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkenyleneZ′R16, C2-C6alkenyleneZ′R16, C2-C6alkynyleneZ′R16, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, C5-C10heteroaryl, C1-C6alkenyleneC3-C7cycloalkyl, C1-C6alkenyleneC3-C10heterocycloalkyl, C1-C6alkyleneC6-C10aryl, and C1-C6alkyleneC5-C10heteroaryl, the latter eight groups being optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OR17, and C(O)R17;
- or
- R11 and R12 are taken together with the nitrogen atom therebetween to form a monocyclic 3- to 7-membered heterocyclic ring optionally comprising 1 to 3 additional ring heteromoieties selected from O, S, S(O), SO2, N, and NR18 and/or optionally comprising one or two C═O groups, wherein said monocyclic 3- to 7-membered heterocyclic ring is further optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OH, OC1-C6alkyl, C1-C6alkenyleneOH, and C1-C6alkenyleneOC1-C6alkyl;
- Z is selected from O, C(O), NR19C(O), NR18C(O)O, OC(O)NR19, and NR19;
- each Z′ is independently selected from O, C(O), NR20C(O), NR20C(O)O, C(O)NR20, OC(O)NR20, and NR20;
- R14 is selected from H, C1-C6alkyl, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, and C5-C10heteroaryl, the latter four groups being optionally substituted with one to four substituents independently selected from halo, C1-C4alkyl, OC1-C4alkyl, and C(O)C1-C4alkyl;
- R15 is selected from H and C1-C6alkyl;
- each R16 is independently selected from H, C1-C6alkyl, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, and C5-C10heteroaryl, the latter four groups being optionally substituted with one to four substituents independently selected from halo, C1-C4alkyl, OC1-C4alkyl, and C(O)C1-C4alkyl;
- each R17 is independently selected from H and C1-C6alkyl;
- each R18 is independently selected from H and C1-C6alkyl;
- R19 is selected from H and C1-C6alkyl;
- each R20 is independently selected from H and C1-C6alkyl;
- and
- available hydrogen atoms of R2, R4, R5, R6, R7 R8, R9, R10, R11, R12, R14, R15, R16, R17, R18, R19, and R20 are optionally replaced with a halogen atom and/or available hydrogen atoms of R1, R2, R3, R4, R5, R6, R7 R8, R9, R10, R11, R12, R14, R15, R16, R17, R18, R19, and R20 are optionally replaced with deuterium;
- provided when R1 is H, R2, R3, R4, R5, R7, R8, R9, and R10 are H or D, and R6 is H, C1-4alkyl, or C1-4deuteroalkyl, then R11 and R12 are not H, C1-4alkyl, or C1-4deuteroalkyl;
- and
- provided when R1, R2, R3, R4, R5, R7, R8, R9, and R10 are H or D, and R6 is CH3 or CHF2, then R11 and R12 are not CH3 or CD3.
28 more elements
A compound of Formula (I)
- or a pharmaceutically acceptable salt, solvate, and/or prodrug thereof,
- wherein:
- X is O;
- R1 is H;
- R2 is selected from H, halo, and C1-C6alkyl;
- R3 is H;
- R4 is selected from H, CN, halo, C1-C6alkyl, C2-C6alkenyl, and C2-C6alkynyl;
- R5 is selected from H, CN, halo, C1-C6alkyl, C2-C6alkenyl, and C2-C6alkynyl;
- R6 is selected from H, C1-C10alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkenyleneZR14, C2-C6alkenyleneZR14, C2-C6alkynyleneZR14, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C1-C6alkenyleneC3-C7cycloalkyl, C1-C6alkenyleneC3-C10heterocycloalkyl, and C1-C6alkenyleneC5-C10heteroaryl, the latter five groups being optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OR15, and C(O)R15;
- R7 is selected from H, halo, and C1-C6alkyl;
- R8 is selected from H, halo, and C1-C6alkyl;
- R9 is selected from H and halo;
- R10 is selected from H and halo;
- R11 is selected from H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkyleneZ′R16, C2-C6alkenyleneZ′R16, C2-C6alkynyleneZ′R16, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, C5-C10heteroaryl, C1-C6alkyleneC3-C7cycloalkyl, C1-C6alkenyleneC3-C10heterocycloalkyl, C1-C6alkenyleneC6-C10aryl, and C1-C6alkyleneC5-C10heteroaryl, the latter eight groups being optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OR17, and C(O)R17;
- R12 is selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkyleneZ′R16, C2-C6alkenyleneZ′R16, C2-C6alkynyleneZ′R16, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, C5-C10heteroaryl, C1-C6alkyleneC3-C7cycloalkyl, C1-C6alkyleneC3-C10heterocycloalkyl, C1-C6alkenyleneC6-C10aryl, and C1-C6alkenyleneC5-C10heteroaryl, the latter eight groups being optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OR17, and C(O)R17;
- or
- R11 and R12 are taken together with the nitrogen atom therebetween to form a monocyclic 3- to 7-membered heterocyclic ring optionally comprising 1 to 3 additional ring heteromoieties selected from O, S, S(O), SO2, N, and NR18 and/or optionally comprising one or two C═O groups, wherein said monocyclic 3- to 7-membered heterocyclic ring is further optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OH, OC1-C6alkyl, C1-C6alkyleneOH, and C1-C6alkenyleneOC1-C6alkyl;
- Z is selected from O, C(O), NR19C(O), NR18C(O)O, C(O)NR19, OC(O)NR19, and NR19;
- each Z′ is independently selected from O, C(O), NR20C(O), NR20C(O)O, C(O)NR20, OC(O)NR20, and NR20;
- R14 is selected from H, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, and C5-C10heteroaryl, the latter four groups being optionally substituted with one to four substituents independently selected from halo, C1-C4alkyl, OC1-C4alkyl, and C(O)C1-C4alkyl;
- R15 is selected from H and C1-C6alkyl;
- each R16 is independently selected from H, C1-C6alkyl, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, and C5-C10heteroaryl, the latter four groups being optionally substituted with one to four substituents independently selected from halo, C1-C4alkyl, OC1-C4alkyl, and C(O)C1-C4alkyl;
- each R17 is independently selected from H and C1-C6alkyl;
- each R18 is independently selected from H and C1-C6alkyl;
- R19 is H;
- each R20 is independently selected from H and C1-C6alkyl;
- and
- available hydrogen atoms of R2, R4, R5, R6, R7 R8, R9, R10, R11, R12, R14, R15, R16, R17, R18 R19, and R20 are optionally replaced with a halogen atom and/or available hydrogen atoms of R1, R2, R3, R4, R5, R6, R7 R8, R9, R10, R11, R12, R14, R15, R16, R17, R18, R19, and R20 are optionally replaced with deuterium;
- provided when R1 is H, R2, R3, R4, R5, R7, R8, R9, and R10 are H or D, and R6 is H, C1-4alkyl, or C1-4deuteroalkyl, then R11 and R12 are not H, C1-4alkyl, or C1-4deuteroalkyl;
- and
- provided when R1, R2, R3, R4, R5, R7, R8, R9, and R10 are H or D, and R6 is CH3 or CHF2, then R11 and R12 are not CH3 or CD3.
28 more elements
A compound of Formula (I)
- or a pharmaceutically acceptable salt, solvate, and/or prodrug thereof, wherein:
- X is O;
- R1 is H;
- R2 is selected from H, halo, and C1-C6alkyl;
- R3 is H;
- R4 is selected from H, CN, halo, C1-C6alkyl, C2-C6alkenyl, and C2-C6alkynyl;
- R5 is selected from H, CN, halo, C1-C6alkyl, C2-C6alkenyl, and C2-C6alkynyl;
- R6 is selected from H, C1-C10alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkyleneZR14, C2-C6alkenyleneZR14, C2-C6alkynyleneZR14, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C1-C6alkyleneC3-C7cycloalkyl, C1-C6alkyleneC3-C10heterocycloalkyl, and C1-C6alkyleneC5-C10heteroaryl, the latter five groups being optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OR15, and C(O)R15;
- R7 is selected from H, halo, and C1-C6alkyl;
- R8 is selected from H, halo, and C1-C6alkyl;
- R9 is selected from H and halo;
- R10 is selected from H and halo;
- R11 and R12 are taken together with the nitrogen atom therebetween to form a monocyclic 3- to 7-membered heterocyclic ring optionally comprising 1 to 3 additional ring heteromoieties selected from O, S, S(O), SO2, N, and NR18 and/or optionally comprising one or two C═O groups, wherein said monocyclic 3- to 7-membered heterocyclic ring is further optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OH, OC1-C6alkyl, C1-C6alkyleneOH, and C1-C6alkyleneOC1-C6alkyl;
- Z is selected from O, C(O), NR10C(O), NR18C(O)O, C(O)NR19, OC(O)NR19, and NR19;
- each Z′ is independently selected from O, C(O), NR20C(O), NR20C(O)O, C(O)NR20, OC(O)NR20, and NR20;
- R14 is selected from H, C1-C6alkyl, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, and C5-C10heteroaryl, the latter four groups being optionally substituted with one to four substituents independently selected from halo, C1-C4alkyl, OC1-C4alkyl, and C(O)C1-C4alkyl;
- R15 is selected from H and C1-C6alkyl;
- each R18 is independently selected from H and C1-C6alkyl;
- R19 is selected from H and C1-C6alkyl;
- each R20 is independently selected from H and C1-C6alkyl;
- and
- available hydrogen atoms of R2, R4, R5, R6, R7 R8, R9, R10, R11, R12, R14, R15, R18, R19, and R20 are optionally replaced with a halogen atom and/or available hydrogen atoms of R1, R2, R3, R4, R5, R6, R7 R8, R9, R10, R11, R12, R14, R15, R18, R19, and R20 are optionally replaced with deuterium;
- provided when R1 is H, R2, R3, R4, R5, R7, R8, R9, and R10 are H or D, and R6 is H, C1-4alkyl, or C1-4deuteroalkyl, then R11 and R12 are not H, C1-4alkyl, or C1-4deuteroalkyl;
- and
- provided when R1, R2, R3, R4, R5, R7, R8, R9, and R10 are H or D, and R6 is CH3 or CHF2, then R11 and R12 are not CH3 or CD3.
22 more elements
A compound of Formula (I)
- or a pharmaceutically acceptable salt, solvate, and/or prodrug thereof,
- wherein:
- X is O;
- R1 is H;
- R2 is selected from H, halo, and C1-C6alkyl;
- R3 is H;
- R4 is selected from H, CN, halo, C1-C6alkyl, C2-C6alkenyl, and C2-C6alkynyl;
- R5 is selected from H, CN, halo, C1-C6alkyl, C2-C6alkenyl, and C2-C6alkynyl;
- R6 is selected from H, C1-C10alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkyleneZR14, C2-C6alkenyleneZR14, C2-C6alkynyleneZR14, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C1-C6alkyleneC3-C7cycloalkyl, C1-C6alkyleneC3-C10heterocycloalkyl, and C1-C6alkyleneC5-C10heteroaryl, the latter five groups being optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OR15, and C(O)R15;
- R7 is selected from H, halo, and C1-C6alkyl;
- R8 is selected from H, halo, and C1-C6alkyl;
- R9 is selected from H and halo;
- R10 is selected from H and halo;
- R11 is selected from H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkyleneZ′R16, C2-C6alkenyleneZ′R16, C2-C6alkynyleneZ′R16, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, C5-C10heteroaryl, C1-C6alkyleneC3-C7cycloalkyl, C1-C6alkyleneC3-C10heterocycloalkyl, C1-C6alkyleneC6-C10aryl, and C1-C6alkenyleneC5-C10heteroaryl, the latter eight groups being optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OR17, and C(O)R17;
- R12 is selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkyleneZ′R16, C2-C6alkenyleneZ′R16, C2-C6alkynyleneZ′R16, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, C5-C10heteroaryl, C1-C6alkenyleneC3-C7cycloalkyl, C1-C6alkyleneC3-C10heterocycloalkyl, C1-C6alkyleneC6-C10aryl, and C1-C6alkenyleneC5-C10heteroaryl, the latter eight groups being optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OR17, and C(O)R17;
- or
- R11 and R12 are taken together with the nitrogen atom therebetween to form a bicyclic 7- to 10-membered heterocyclic ring optionally comprising 1 to 3 additional ring heteromoieties selected from O, S, S(O), SO2, N, and NR18 and/or optionally comprising only one C═O group, wherein said bicyclic 7- to 10-membered heterocyclic ring is further optionally substituted with one to four substituents independently selected from halo, C1-C6alkyl, OH, OC1-C6alkyl, C1-C6alkyleneOH, and C1-C6alkyleneOC1-C6alkyl;
- Z is selected from O, C(O), NR19C(O), NR18C(O)O, OC(O)NR19, and NR19;
- each Z′ is independently selected from O, C(O), NR20C(O), NR20C(O)O, C(O)NR20, OC(O)NR20, and NR20;
- R14 is selected from H, C1-C6alkyl, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, and C5-C10heteroaryl, the latter four groups being optionally substituted with one to four substituents independently selected from halo, C1-C4alkyl, OC1-C4alkyl, and C(O)C1-C4alkyl;
- R15 is selected from H and C1-C6alkyl;
- each R16 is independently selected from H, C1-C6alkyl, C3-C7cycloalkyl, C3-C10heterocycloalkyl, C6-C10aryl, and C5-C10heteroaryl, the latter four groups being optionally substituted with one to four substituents independently selected from halo, C1-C4alkyl, OC1-C4alkyl, and C(O)C1-C4alkyl;
- each R17 is independently selected from H and C1-C6alkyl;
- each R18 is independently selected from H and C1-C6alkyl;
- R19 is selected from H and C1-C6alkyl;
- each R20 is independently selected from H and C1-C6alkyl;
- and
- available hydrogen atoms of R2, R4, R5, R6, R7 R8, R9, R10, R11, R12, R14, R15, R16, R17, R18 R19, and R20 are optionally replaced with a halogen atom and/or available hydrogen atoms of R1, R2, R3, R4, R5, R6, R7 R8, R9, R10, R11, R12, R14, R15, R16, R17, R18, R19, and R20 are optionally replaced with deuterium;
- provided when R1 is H, R2, R3, R4, R5, R7, R8, R9, and R10 are H or D, and R6 is H, C1-4alkyl, or C1-4deuteroalkyl, then R11 and R12 are not H, C1-4alkyl, or C1-4deuteroalkyl;
- and
- provided when R1, R2, R3, R4, R5, R7, R8, R9, and R10 are H or D, and R6 is CH3 or CHF2, then R11 and R12 are not CH3 or CD3.
28 more elements
Dependencies are inferred from the claim text.