Treatment of neuropathic pain with 6H-pyrrolo[3,4-d]pyridazine compounds

A compound represented by Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein
• R1 is —C0-6alkyl-aryl, —C0-6alkyl-heteroaryl, —C0-6alkyl-C3-6cycloalkyl, or —C0-6alkyl-heteroC3-7cycloalkyl, optionally substituted with 1-6 independent halogen, —CN, NO2, —C1-6alkyl, —C0-6alkyl-C3-6cycloalkyl, —C0-6alkyl-heteroC3-7cycloalkyl, —OR6, —NR6R7, —C(═NR6)NR7R8, —N(—NR88R6)NR7R8, —NR6COR7, —NR6CO2R7, —NR6SO2R88, —NR6CONR7R8, —SR88, —SOR88, —SO2R88, —SO2NR6R7, —COR6, —CO2R6, —CONR6R7, —C(═NR6)R7, or —C(═NOR6)R7 substituents;
• R2, and R3, each independently is —C1-6alkyl, —C0-6alkyl-aryl, —C0-6alkyl-heteroaryl, —C0-6alkyl-C3-6cycloalkyl, or —C0-6alkyl-heteroC3-7cycloalkyl, optionally substituted with 1-6 independent halogen, —CN, NO2, —C1-6alkyl, —OR6, —NR6R7, —C(═NR6)NR7R8, —N(—NR88R6)NR7R8, —NR6COR7, —NR6CO2R7, —NR6SO2R88, —NR6CONR7R8, —SR88, —SOR88, —SO2R88, —SO2NR6R7, —COR6, —CO2R6, —CONR6R7, —C(═NR6)R7, or —C(═NOR6)R7 substituents;
• R4, and R5 each independently is —C0-6alkyl, —C0-6alkyl-aryl, —C0-6alkyl-heteroaryl, —C0-6alkyl-C3-6cycloalkyl, or —C0-6alkyl-hetero C3-7cycloalkyl, optionally substituted with 1-6 independent halogen, —CN, NO2, —C1-6alkyl, —OR6, —NR6R7, —C(═NR6)NR7R8, —N(—NR88R6)NR7R8, —NR6COR7, —NR6CO2R7, —NR6SO2R88, —NR6CONR7R8, —SR88, —SOR88, —SO2R88, —SO2NR6R7, —COR6, —CO2R6, —CONR6R7, —C(═NR6)R7, or —C(═NOR6)R7 substituents;
• and
• R6, R7, R8, and R88 each independently is —C0-6alkyl, —C3-7cycloalkyl, heteroaryl, or aryl;
• optionally substituted with 1-5 independent halogen, —CN, —C1-6alkyl, —O(C0-6alkyl), —O(C3-7cycloalkyl), —O(aryl), —N(C0-6alkyl)(C0-6alkyl), —N(C0-6alkyl)(C3-7cycloalkyl), or —N(C0-6alkyl)(aryl) substituents, wherein when the carbon atom in —C0-6alkyl equals “0” then no alkyl is present;
• provided that the compound is not
• 6-methyl-6H-pyrrolo[3,4-d]pyridazine,
• 1,4,5,7-tetramethyl-6-phenyl-6H-pyrrolo[3,4-d]pyridazine,
• 1,4,5-trimethyl-6,7-diphenyl-6H-pyrrolo[3,4-d]pyridazine,
• 5,7-dimethyl-1,4,6-triphenyl-6H-pyrrolo[3,4-d]pyridazine,
• 5-methyl-1,4,6,7-tetraphenyl-6H-pyrrolo[3,4-d]pyridazine,
• 1,4-bis-(4-methoxy-phenyl)-5,7-dimethyl-6-phenyl-6H-pyrrolo[3,4-d]pyridazine,
• 1,4-bis-(4-methoxy-phenyl)-5-methyl-6,7-diphenyl-6H-pyrrolo[3,4-d]pyridazine,
• 1,4-diethyl-5,7-dimethyl-6-phenyl-6H-pyrrolo[3,4-d]pyridazine,
• 1,4,5,7-tetramethyl-6H-pyrrolo[3,4-d]pyridazine,
• N-(1,4,5,7-tetramethyl-pyrrolo[3,4-d]pyridazin-6-yl)-benzamide,
• 1,4,5,7-tetramethyl-pyrrolo[3,4-d]pyridazin-6-ylamine picrate,
• 1,4,5,7-tetramethyl-pyrrolo[3,4-d]pyridazin-6-ylamine,
• 5,7-dimethyl-6-phenyl-6H-pyrrolo[3,4-d]pyridazine,
• 5,7-dimethyl-2-phenacyl-6H-pyrrolo[3,4-d]pyridazinium bromide,
• 2-(2-methoxycarbonylvinyl)-5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazinium tetrafloroborate
• 5,7-diphenyl-6H-pyrrolo[3,4-d]pyridazine,
• 5,6,7-trimethyl-6H-pyrrolo[3,4-d]pyridazine,
• 1,4-diphenyl-7,8,9,10-tetrahydro-pyridazino[4,5-a]indolizine,
• 5-methyl-1,4-diphenyl-7,8,9,10-tetrahydro-pyridazino[4,5-a]indolizine,
• 6-benzyl-1,4-diphenyl-5-p-tolyl-6H-pyrrolo[3,4-d]pyridazine,
• 6-benzyl-5-(2-chloro-phenyl)-1,4-diphenyl-6H-pyrrolo[3,4-d]pyridazine,
• 1,4,5,6,7-pentaphenyl-6H-pyrrolo[3,4-d]pyridazine,
• 6,7,10,11-tetraphenyl-pyridazino[4′,5′:3,4]pyrrolo[1,2-a]quinoxaline,
• 11-(4-nitro-phenyl)-6,7,10-triphenyl-pyridazino[4′,5′:3,4]pyrrolo[1,2-a]quinoxaline,
• 6-benzyl-1,4,5-triphenyl-6H-pyrrolo[3,4-d]pyridazine,
• 9,12-diphenyl-pyridazino[4′, 5′:3,4]pyrrolo[2, 1-a]isoquinoline,
• 5-methylsulfanyl-1,4,6,7-tetraphenyl-6H-pyrrolo[3,4-d]pyridazine,
• 1,4,6,7-tetraphenyl-6H-pyrrolo[3,4-d]pyridazine-5-carboxylic acid ethyl ester,
• 7,10-diphenyl-pyridazino[4′,5′:3,4]pyrrolo[1,2-a]quinoline,
• 11,14-diphenyl-pyridazino[4′,5′:3,4]pyrrolo[1,2-f]phenanthridine,
• 1-oxo-7-oxy-6b,11b-dihydro(pyridazino[4′,5′-c]-pyrrolo)[2.1-c]benzoxazine-1,4,
• 10-methyl-1,4-diphenyl-8,9-dihydro-7H-benzo(ef)pyridazino[4,5-a]cycl[3.3.2]azine,
• 11-methyl-1,4-diphenyl-7,8,9,10-tetrahydrocyclohepta(ef)pyridazino[4,5-a]cycl[3.3.2]azine,
• 1,4-dichloro-5,6,7-trimethyl-6H-pyrrolo[3,4-d]pyridazine,
• 1-chloro-4-ethoxy-5,6,7-trimethyl-6H-pyrrolo[3,4-d]pyridazine,
• 1-chloro-5,6,7-trimethyl-6H-pyrrolo[3,4-d]pyridazinium chloride,
• 1-ethoxy-2,5,6,7-tetramethyl-6H-pyrrolo[3,4-d]pyridazinium tetrafluoroborate,
• 1-ethoxy-5,6,7-trimethyl-2H,6H-pyrrolo[3,4-d]pyridazinium tetrafluoroborate,
• 1-ethoxy-3-ethyl-5,6,7-trimethyl-6H-pyrrolo[3,4-d]pyridazinium tetrafluoroborate,
• 1-ethoxy-5,6,7-trimethyl-6H-pyrrolo[3,4-d]pyridazine,
• 5-cyano-1,4-dimethylpyridazino[4,5-a]indolizine,
• 1,4-dimethyl-6-phenyl-2,3,8a-triaza-fluorene-9-carbonitrile,
• 6-benzolyl-1,4-dimethyl-2,3,8a-triaza-fluorene-9-carbonitrile,
• 6-benzyl-1,4-diphenyl-2,3,8a-triaza-fluorene-9-carbonitrile,
• 1,4,6-trimethyl-2,3,8a-triaza-fluorene-9-carbonitrile,
• 5-cyano-1,4-diphenylpyridazino[4,5-a]indolizine,
• 6-methyl-1,4-diphenyl-2,3,8a-triaza-fluorene-9-carbonitrile,
• 6-benzoyl-1,4-diphenyl-2,3,8a-triaza-fluorene-9-carbonitrile,
• 1,4,6-triphenyl-2,3,8a-triaza-fluorene-9-carbonitrile,
• 5,7-dimethyl-1,4-diphenyl-2,3,8a-triaza-fluorene-9-carbonitrile,
• 9,12-diphenyl-pyridazino[4′,5′:3,4]pyrrolo[2,1-a]isoquinoline-8-carbonitrile,
• dimethyl 3,12,13,17-tetramethyl-72,73-diazabenzo[g]porphyrin-2,18-dipropionate,
• 5,6-dihydro-2,3-dimethoxypyridazino[4′,5′:3,4]pyrrolo[2,1-a]isochinolin-9-ol,
• 5,6-dihydro-2,3-dimethoxypyridazino[4′,5′:3,4]pyrrolo[2,1-a]isochinolin-9-ol-hydrochloride,
• 3-methyl-6,9-diphenylthiazolo[3′,2′:1,2]pyrrolo[3,4d]pyridine, or
• 1,4-diphenylpyridazino[4′,5′:3,4]pyrrolo[2,1-b]benzothiazole;
• and
• is not selected from the following table: