Aza (indole)-, benzothiophene-, and benzofuran-3-sulfonamides

A method for treating a syndrome or disorder associated with GPR17, wherein the syndrome or disorder is a demyelination disorder of the central nervous system, the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound corresponding in structure to Formula I-2:

• or a pharmaceutically acceptable salt, solvate, isotope or co-crystal thereof,
• wherein:
• XI is N or C(R7),
• X2 is NH, S or O,
• X3 is N or C(R12),
• R2 is selected from hydrogen, fluoro, chloro, bromo, iodo and methoxy,
• R4 is selected from hydrogen, methoxy and halogen,
• R5 is selected from hydrogen, halogen, cyano, C1-3 alkyl, C1-3 alkoxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylsulfinyl, and C1-3alkylsulfonyl, wherein each alkyl or alkoxy may optionally be substituted one or more times with a substituent selected from halogen, C1-3 alkoxy, cyano, azido, hydroxyl, C1-3alkylamino and di(C1-3alkyl)amino, or R5 forms a ring together with R6,
• R6 is selected from hydrogen, fluoro, chloro, bromo, iodo, cyano, azido, nitro, unsubstituted or substituted C1-3 alkyl, unsubstituted or substituted C1-3 alkoxy, unsubstituted or substituted C2-3 alkenyl, unsubstituted or substituted C2-3 alkynyl, unsubstituted or substituted C1-3 alkylcarbonyl, unsubstituted or substituted C1-3 alkoxycarbonyl, unsubstituted or substituted C1-3 alkylsulfinyl, unsubstituted or substituted C1-3 alkylsulfonyl, unsubstituted or substituted benzylsulfonyl, unsubstituted or substituted benzylsulfinyl, unsubstituted or substituted C3-7 cycloalkyl, unsubstituted or substituted C3-7 cycloalkyl(C1-3)alkyl, unsubstituted or substituted C3-7 heterocycloalkyl, unsubstituted or substituted C3-7 heterocycloalkyl(C1-3)alkyl, unsubstituted or substituted C3-6 cycloalkoxy, unsubstituted or substituted C3-6 heterocycloalkoxy, unsubstituted or substituted C1-5alkoxy(C1-5)alkyl, unsubstituted or substituted C1-3alkoxy(C1-3)alkoxy, unsubstituted or substituted (C3-6)cycloalkyl(C1-3)alkoxy, unsubstituted or substituted (C3-6)heterocycloalkyl(C1-3)alkoxy, unsubstituted or substituted phenyl, -unsubstituted or substituted phenyloxy, unsubstituted or substituted thienyl, unsubstituted or substituted pyridyl, unsubstituted or substituted oxazole, unsubstituted or substituted thiazole, unsubstituted or substituted isoxazole, unsubstituted or substituted phenyl(C1-3)alkoxy,
• wherein each optional substitution in R6 is selected from one or more of the group consisting of fluoro, chloro, bromo, unsubstituted or fluorinated methyl, unsubstituted or fluorinated methoxy, hydroxy and cyano, or
• (i) R6 forms together with R7 and the carbon atoms to which R6 and R7 are attached, an unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted cyclopentyl or unsubstituted or substituted cyclohexyl,
• wherein each substitution, if present, is selected from halogen, hydroxy, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl(C1-3)alkyl, C3-7 heterocycloalkyl(C1-3)alkyl, C1-6 alkoxy, and C1-6 alkoxy(C1-3)alkyl, wherein each alkyl or alkoxy can be unsubstituted or substituted with one or more substituents selected from halogen and C1-3 alkoxy,
• or
• (ii) R6 forms together with R5 and the carbon atoms to which R6 and R5 are attached, a 1,3-dioxolane which may be unsubstituted or substituted with one or two substituents selected from fluoro and methyl,
• R7 is selected from hydrogen, halogen, cyano, C1-3 alkyl, C1-3 alkoxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylsulfonyl, C1-3 alkylsulfinyl, C5-6 heteroaryl, and C5-6 heteroaryl(C1-3) alkoxy, wherein each alkyl or alkoxy moiety can be unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, halo(C1-6)alkoxy, and C1-3 alkoxy, and wherein each heteroaryl can be unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, methyl, hydroxy, and methoxy, or R7 forms a ring together with R6,
• R8 is selected from hydrogen, C1-3 alkyl, C1-3 alkoxy, cyano, and halogen, wherein each alkyl or alkoxy can be unsubstituted or substituted with one or more substituents selected from halogen, cyano and methoxy, or R8 forms a ring system together with R9, as described herein,
• R9 is selected from hydrogen, C1-3 alkyl, C2-3 alkoxy, fluoro, chloro, bromo and iodo, wherein each alkyl or alkoxy can be unsubstituted or substituted with one or more substituents selected from halogen and methoxy,
• or R9 forms together with R8 or R10 and the ring to which they are attached a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole, 1,3-benzothiazole, 1,3-benzoxazole which may be unsubstituted or may be partially hydrogenated and substituted with oxo, 2-oxo-2,3-dihydro-1,3-benzoxazol, 1,3-benzodioxole which may be unsubstituted or substituted with one or two substituents selected from fluoro and methyl, 2,2-difluoro-1,3-benzodioxol, 2,3-dihydrobenzothiophene which may be unsubstituted or substituted with one or two oxo groups, 1,1-dioxido-2,3-dihydro-1-benzothiophen, 1,3-dihydro-2-benzofuran which may be unsubstituted or substituted with one or two groups selected from oxo, fluoro and methyl, 3-oxo-1,3-dihydro-2-benzofuran, 1-methyl-3-oxo-1,3-dihydro-2-benzofuran, dihydroisoindol which may be unsubstituted or substituted with one or more substituents selected from oxo, fluoro and methyl, and 3-oxo-2,3-dihydro-1H-isoindol,
• R10 is selected from hydrogen, fluoro, chloro, bromo, iodo, C1-5 alkyl, C1-5 alkoxy, C2-4 alkenyl, C2-4 alkynyl, C3-4 cycloalkyl, C3-4 heterocycloalkyl, cyano, cyanomethyl, cyanomethoxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, azido, pentafluorosulfanyl, and nitro, wherein each alkyl, alkenyl, alkynyl or alkoxy can be unsubstituted or substituted with one or more substituents selected from halogen, unsubstituted or fluorinated C1-3 alkoxy, unsubstituted or fluorinated C1-3 alkoxycarbonyl, unsubstituted or fluorinated C1-3 alkylcarbonyl, cyano, hydroxy, cyclopropyl and pyridyl, wherein the pyridyl may be optionally substituted with halogen, unsubstituted or fluorinated methyl and/or unsubstituted or fluorinated methoxy, and wherein any cycloalkyl or heterocycloalkyl can be unsubstituted or substituted with a group selected from halogen, cyano, hydroxy(C1-2)alkyl, C1-2alkoxy and C1-2alkoxycarbonyl, or R10 forms a ring system together with R9,
• R11 is selected from hydrogen, C1-3 alkyl, C1-3 alkoxy, fluoro, chloro, bromo, iodo, cyano, C1-3 alkylcarbonyl, and C1-3 alkoxycarbonyl, wherein each alkyl and alkoxy can be unsubstituted or substituted with one or more substituents selected from fluoro, chloro, bromo, iodo and C1-3 alkoxy,
• R12, if present, is selected from hydrogen, C1-3 alkyl, C1-3 alkoxy, fluoro, chloro, bromo, and iodo, wherein each alkyl and alkoxy can be unsubstituted or substituted with one or more substituents selected from fluoro, chloro, bromo, iodo and C1-3 alkoxy.