Indoline derivatives as serotonergic agents useful for the treatment of disorders related thereto

A pharmaceutical composition comprising one or more compounds of Formula I or a pharmaceutically acceptable salt, solvate, and/or prodrug thereof and a pharmaceutically acceptable carrier, wherein Formula I is

• wherein:
• R1 is selected from C(O)R7, CO2R7, C(O)N(R7)(R7′), S(O)R7, SO2R7, C1-6alkyleneR7, and R7;
• Q is selected from Q1, Q2, Q2′, Q4, and Q5:
• is a single bond or a double bond provided that when in Q1 is a double bond then R9 and R15 are not present, and when in Q2 is a double bond then R17 and R25 are not present, and when in Q2′ is a double bond then R16′ and R25′ are not present;
• over a bond means that the bond is attached to a remaining portion of the compound;
• R2, R2, and R2″ are independently selected from H, halo, C1-6alkyl, C1-6alkoxy, C1-6alkyleneN(R2a)(R2b), and SC1-6alkyl;
• R2a and R2b are independently selected from H and C1-6alkyl;
• R3, R4, R5, and R6 are independently selected from H, halo, N(R5′)(R6′), C1-6alkyl, C1-6alkoxy, C1-6alkyleneN(R5′)(R6′), and SC1-6alkyl, the latter four groups being optionally substituted with one or two substituents independently selected from OH and C1-6alkoxy, or
• two adjacent R3, R4, R5, and R6 are linked together to form O—(CH2)1-2O and the remaining of R3, R4, R5, and R6 are independently selected from H, halo, C1-6alkyl, C1-6alkoxy, N(R5′)(R6′), C1-6alkyleneN(R5′)(R6′), and SC1-6alkyl, or
• one of R3, R4, R5, and R6 is selected from A, O-A, and C1-4alkylene A and the remaining of R3, R4, R5, and R6 are independently H or halo;
• R5′ and R6′ are independently selected from H and C1-6alkyl;
• A is selected from phenyl, C3-6cycloalkyl, 3- to 6-membered heterocycloalkyl comprising 1 to 4 heteromoieties independently selected from O, S, S(O), SO2, N, and NR54, and 5- to 6-membered heteroaryl comprising 1 to 4 heteromoieties independently selected from O, S, S(O), SO2, N, and NR54, wherein the phenyl, C3-10cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-4alkyl, OC1-4alkyl, N(R54a)(R54b), C1-4alkyleneN(R54a)(R54b), and SC1-4alkyl;
• R7 is selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, phenyl, C3-6cycloalkyl, 3- to 6-membered heterocycloalkyl comprising 1 to 4 heteromoieties independently selected from O, S, N, and NR7″, and 5- to 6-membered heteroaryl comprising 1 to 4 heteromoieties independently selected from O, S, N, and NR7″, wherein the latter 7 groups are optionally substituted with one or more substituents independently selected from halo, OR55, N(R55)(R56), and SR55 and/or the C1-6alkyl is optionally interrupted by one to three heteromoieties independently selected from O, C(O), CO2, and NR57;
• R7′ is selected from H and C1-6alkyl;
• R7″ is selected from H and C1-6alkyl;
• R8, R9, R10, R11, R13, R14, R15, R16, R16′, R17, R7′, R18, R19′, R19, R19′, R21, R22′, R22, R22′, R23, R23′, R24, R24′, R25, R25, R32, R33, R34, R36, R37, R38, R39, R40, R41, R42, R43, R44, R46, R47, R48, R49, R50, R51, R52, and R53 are independently selected from H, halo, and C1-6alkyl;
• R12, R20, R20′, R35, and R45 are independently selected from H, C1-6alkyl, and C(O)C1-6alkyl;
• R54, R55, R55, and R57 are independently selected from H and C1-6alkyl;
• R54a and R54b are independently selected from H and C1-6alkyl;
• and
• available hydrogen atoms are optionally and independently substituted with a fluorine atom or a chlorine atom and available atoms are optionally substituted with alternate isotope thereof.

A method of treating a central nervous system (CNS) disease, disorder, or condition and/or a neurological disease, disorder, or condition comprising administering a therapeutically effective amount of one or more compounds of Formula I or a pharmaceutically acceptable salt, solvate, and/or prodrug thereof to a subject in need thereof, wherein Formula I is

• wherein:
• R1 is selected from C(O)R7, CO2R7, C(O)N(R7)(R7′), S(O)R7, SO2R7, C1-6alkyleneR7, and R7;
• Q is selected from Q1, Q2, Q2′, Q4, and Q5:
• is a single bond or a double bond provided that when in Q1 is a double bond then R9 and R15 are not present, and when in Q2 is a double bond then R17 and R25 are not present, and when in Q2′ is a double bond then R16′ and R25′ are not present;
• over a bond means that the bond is attached to a remaining portion of the compound;
• R2, R2, and R2″ are independently selected from H, halo, C1-6alkyl, C1-6alkoxy, C1-6alkyleneN(R2a)(R2b), and SC1-6alkyl;
• R2a and R2b are independently selected from H and C1-6alkyl;
• R3, R4, R5, and R6 are independently selected from H, halo, N(R5′)(R6′), C1-6alkyl, C1-6alkoxy, C1-6alkyleneN(R5′)(R6′), and SC1-6alkyl, the latter four groups being optionally substituted with one or two substituents independently selected from OH and C1-6alkoxy, or two adjacent R3, R4, R5, and R6 are linked together to form O—(CH2)1-2O and the remaining of R3, R4, R5, and R6 are independently selected from H, halo, C1-6alkyl, C1-6alkoxy, N(R5′)(R6, C1-6alkyleneN(R5′)(R6′), and SC1-6alkyl, or
• one of R3, R4, R5, and R6 is selected from A, O-A, and C1-4alkylene A and the remaining of R3, R4, R5, and R6 are independently H or halo;
• R5′ and R6′ are independently selected from H and C1-6alkyl;
• A is selected from phenyl, C3-6cycloalkyl, 3- to 6-membered heterocycloalkyl comprising 1 to 4 heteromoieties independently selected from O, S, S(O), SO2, N, and NR54, and 5- to 6-membered heteroaryl comprising 1 to 4 heteromoieties independently selected from O, S, S(O), SO2, N, and NR54, wherein the phenyl, C3-10cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-4alkyl, OC1-4alkyl, N(R54a)(R54b), C1-4alkyleneN(R54a)(R54b), and SC1-4alkyl;
• R7 is selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, phenyl, C3-6cycloalkyl, 3- to 6-membered heterocycloalkyl comprising 1 to 4 heteromoieties independently selected from O, S, N, and NR7″, and 5- to 6-membered heteroaryl comprising 1 to 4 heteromoieties independently selected from O, S, N, and NR7″, wherein the latter 7 groups are optionally substituted with one or more substituents independently selected from halo, OR55, N(R55)(R56), and SR55 and/or the C1-6alkyl is optionally interrupted by one to three heteromoieties independently selected from O, C(O), CO2, and NR57;
• R7′ is selected from H and C1-6alkyl;
• R7″ is selected from H and C1-6alkyl;
• R8, R9, R10, R11, R13, R14, R15, R16, R16′, R17, R7′, R18, R19′, R19, R19′, R21, R22′, R22, R22′, R23, R23′, R24, R24′, R25, R25, R32, R33, R34, R36, R37, R38, R39, R40, R41, R42, R43, R44, R46, R47, R48, R49, R50, R51, R52, and R53 are independently selected from H, halo, and C1-6alkyl;
• R12, R20, R20′, R35, and R45 are independently selected from H, C1-6alkyl, and C(O)C1-6alkyl;
• R54, R55, R55, and R57 are independently selected from H and C1-6alkyl;
• R54a and R54b are independently selected from H and C1-6alkyl;
• and
• available hydrogen atoms are optionally and independently substituted with a fluorine atom or a chlorine atom and available atoms are optionally substituted with alternate isotope thereof.