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    • 3. 发明申请
    • HETEROCYCLIC COMPOUNDS SUITABLE FOR TREATING DISORDERS THAT RESPOND TO MODULATION OF THE DOPAMINE D3 RECEPTOR
    • 适用于治疗多巴胺D3受体调节障碍的异种化合物
    • US20110160176A1
    • 2011-06-30
    • US12868480
    • 2010-08-25
    • Karla DrescherAndreas HauptLiliane UngerSean C. TurnerWilfried BrajeRoland GrandelChristophe HenryGisela BackfischArmin BeyerbachWilfried Lubisch
    • Karla DrescherAndreas HauptLiliane UngerSean C. TurnerWilfried BrajeRoland GrandelChristophe HenryGisela BackfischArmin BeyerbachWilfried Lubisch
    • A61K31/397C07D207/08A61K31/40C07D401/02C07D205/02C07D403/02A61K31/506C07D417/02A61K31/433C07D413/14A61K31/422C07D211/08A61K31/445A61P25/28
    • C07D413/14C07D205/04C07D207/09C07D211/28C07D401/04C07D401/12C07D403/04C07D405/12C07D409/12C07D413/10C07D413/12
    • The invention relates to compounds of the formula (I) wherein n is 0, 1 or 2; G is CH2 or CHR3; R1 is H, C,-C6-alkyl, C,-C6-alkyl substituted by C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, fluorinated C,-C6-alkyl, C3-C6-cycloalkyl, fluorinated C3-C6-cycloalkyl, C3-C6 alkenyl, fluorinated C3-C6-alkenyl, formyl, acetyl or propionyl; R2, R3 and R4 are, independently of each other, H, methyl, fluoromethyl, difluoromethyl, or trifluoromethyl; A is phenylene, pyridylene, pyrimidylene, pyrazinylene, pyridazinylene or thiophenylene, which can be substituted by one or more substituents selected from halogen, methyl, methoxy and CF3; E is NR5 or CH2, wherein R5 is H or C1-C3-alkyl; Ar is a cyclic radical selected from the group consisting of phenyl, a 5- or 6-membered heteroaromatic radical comprising as ring members 1, 2 or 3 heteroatoms selected from N, O and S and a phenyl ring fused to a saturated or unsaturated 5- or 6-membered carbocyclic or heterocyclic ring, where the heterocyclic ring comprises as ring members 1, 2 or 3 heteroatoms selected from N, O and S and/or 1, 2 or 3 heteroatom-containing groups each independently selected from NR8, where R8 is H, C1-C4-alkyl, fluorinated C1-C4-alkyl, C1-C4alkylcarbonyl or fluorinated C1-C4-alkylcarbonyl, and where the cyclic radical Ar may carry 1, 2 or 3 substituents Ra, wherein the variable Ra has the meanings given in the claims and in the description; and physiologically tolerated acid addition salts thereof. The invention also relates to the use of a compound of the formula I or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for the treatment of a medical disorder susceptible to treatment with a dopamine D3 receptor ligand.
    • 本发明涉及式(I)化合物,其中n为0,1或2; G是CH 2或CHR 3; R 1是被C 3 -C 6 - 环烷基取代的C 1 -C 6 - 烷基,C 1 -C 6 - 烷基,C 1 -C 6羟基烷基,氟化C 1 -C 6 - 烷基,C 3 -C 6环烷基,氟化C 3 -C 6 - 环烷基,C3-C6烯基,氟化C3-C6-烯基,甲酰基,乙酰基或丙酰基; R2,R3和R4彼此独立地为H,甲基,氟甲基,二氟甲基或三氟甲基; A是可以被一个或多个选自卤素,甲基,甲氧基和CF 3的取代基取代的亚苯基,亚吡啶基,亚嘧啶基,吡嗪基,哒嗪基或噻吩基; E是NR5或CH2,其中R5是H或C1-C3-烷基; Ar是选自苯基,5或6元杂芳族基团的环状基团,其包含选自N,O和S的环成员1,2或3个杂原子和与饱和或不饱和5 - 或6-元碳环或杂环,其中杂环包含作为环成员1,2或3个选自N,O和S的杂原子和/或1,2或3个各自独立地选自NR8的含杂原子的基团,其中 R8是H,C1-C4-烷基,氟化C1-C4-烷基,C1-C4烷基羰基或氟化C1-C4-烷基羰基,其中环状基团Ar可以带有1,2或3个取代基Ra,其中变量Ra具有 在权利要求和说明书中给出的含义; 和其生理学耐受的酸加成盐。 本发明还涉及式I化合物或其药学上可接受的盐在制备用于治疗易受多巴胺D3受体配体治疗的医学疾病的药物组合物中的用途。
    • 4. 发明授权
    • Heterocyclic compounds suitable for treating disorders that respond to modulation of the dopamine D3 receptor
    • 适用于治疗对多巴胺D3受体调节作出反应的疾病的杂环化合物
    • US08470810B2
    • 2013-06-25
    • US12868480
    • 2010-08-25
    • Karla DrescherAndreas HauptLiliane UngerSean C. TurnerWilfried BrajeRoland GrandelChristophe HenryGisela BackfischArmin BeyerbachWilfried Lubisch
    • Karla DrescherAndreas HauptLiliane UngerSean C. TurnerWilfried BrajeRoland GrandelChristophe HenryGisela BackfischArmin BeyerbachWilfried Lubisch
    • A61K31/397C07D413/02
    • C07D413/14C07D205/04C07D207/09C07D211/28C07D401/04C07D401/12C07D403/04C07D405/12C07D409/12C07D413/10C07D413/12
    • The invention relates to compounds of the formula (I) wherein n is 0, 1 or 2; G is CH2 or CHR3; R1 is H, C,-C6-alkyl, C,-C6-alkyl substituted by C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, fluorinated C,-C6-alkyl, C3-C6-cycloalkyl, fluorinated C3-C6-cycloalkyl, C3-C6 alkenyl, fluorinated C3-C6-alkenyl, formyl, acetyl or propionyl; R2, R3 and R4 are, independently of each other, H, methyl, fluoromethyl, difluoromethyl, or trifluoromethyl; A is phenylene, pyridylene, pyrimidylene, pyrazinylene, pyridazinylene or thiophenylene, which can be substituted by one or more substituents selected from halogen, methyl, methoxy and CF3; E is NR5 or CH2, wherein R5 is H or C1-C3-alkyl; Ar is a cyclic radical selected from the group consisting of phenyl, a 5- or 6-membered heteroaromatic radical comprising as ring members 1, 2 or 3 heteroatoms selected from N, O and S and a phenyl ring fused to a saturated or unsaturated 5- or 6-membered carbocyclic or heterocyclic ring, where the heterocyclic ring comprises as ring members 1, 2 or 3 heteroatoms selected from N, O and S and/or 1, 2 or 3 heteroatom-containing groups each independently selected from NR8, where R8 is H, C1-C4-alkyl, fluorinated C1-C4-alkyl, C1-C4alkylcarbonyl or fluorinated C1-C4-alkylcarbonyl, and where the cyclic radical Ar may carry 1, 2 or 3 substituents Ra, wherein the variable Ra has the meanings given in the claims and in the description; and physiologically tolerated acid addition salts thereof. The invention also relates to the use of a compound of the formula I or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for the treatment of a medical disorder susceptible to treatment with a dopamine D3 receptor ligand.
    • 本发明涉及式(I)化合物,其中n为0,1或2; G是CH 2或CHR 3; R 1是被C 3 -C 6 - 环烷基取代的C 1 -C 6 - 烷基,C 1 -C 6 - 烷基,C 1 -C 6羟基烷基,氟化C 1 -C 6 - 烷基,C 3 -C 6环烷基,氟化C 3 -C 6 - 环烷基,C3-C6烯基,氟化C3-C6-烯基,甲酰基,乙酰基或丙酰基; R2,R3和R4彼此独立地为H,甲基,氟甲基,二氟甲基或三氟甲基; A是可以被一个或多个选自卤素,甲基,甲氧基和CF 3的取代基取代的亚苯基,亚吡啶基,亚嘧啶基,吡嗪基,哒嗪基或噻吩基; E是NR5或CH2,其中R5是H或C1-C3-烷基; Ar是选自苯基,5或6元杂芳族基团的环状基团,其包含选自N,O和S的环成员1,2或3个杂原子和与饱和或不饱和5 - 或6-元碳环或杂环,其中杂环包含作为环成员1,2或3个选自N,O和S的杂原子和/或1,2或3个各自独立地选自NR8的含杂原子的基团,其中 R8是H,C1-C4-烷基,氟化C1-C4-烷基,C1-C4烷基羰基或氟化C1-C4-烷基羰基,其中环状基团Ar可以带有1,2或3个取代基Ra,其中变量Ra具有 在权利要求和说明书中给出的含义; 和其生理学耐受的酸加成盐。 本发明还涉及式I化合物或其药学上可接受的盐在制备用于治疗易受多巴胺D3受体配体治疗的医学疾病的药物组合物中的用途。