公开(公告)号：US08598211B2

公开(公告)日：2013-12-03

申请号：US12972679

申请日：2010-12-20

申请人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Möller ,  Wilfried Hornberger ,  Gisela Backfisch ,  Yanbin Lao ,  Marjoleen Nijsen

发明人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Möller ,  Wilfried Hornberger ,  Gisela Backfisch ,  Yanbin Lao ,  Marjoleen Nijsen

IPC分类号： A61K31/4439 ,  C07D401/04

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D413/14

摘要： The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity.The carboxamide compounds are compounds of the general formula I in which R1, R2, R3 R4, R5, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R1 is optionally substituted phenyl-C1-C2-alkyl or hetaryl-C1-C2-alkyl, R2 is optionally substituted aryl, hetaryl, aryl-C1-C6-alkyl, aryl-C2-C6-alkenyl or hetaryl-C1-C4-alkyl, R3 is C3-C4-alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C2-alkyl, C3-C6-heterocycloalkyl-C1-C2-alkyl, phenyl-C1-C3-alkyl, pyridin-2-yl-C1-C3-alkyl or 1,3-benzoxazol-2-yl-methyl, R4 and R5 independently of one another are halogen, CF3, CHF2, CH2F, C1-C2-alkyl or C1-C2-alkoxy, and m and n independently of one another are 0 or 1.

摘要翻译： 本发明涉及新的羧酰胺化合物及其用于制备药物的用途。 羧酰胺化合物是钙蛋白酶（钙依赖性半胱氨酸蛋白酶）的抑制剂。 因此，本发明还涉及这些羧酰胺化合物用于治疗与升高的钙蛋白酶活性相关的病症的用途。 羧酰胺化合物是通式I的化合物，其中R 1，R 2，R 3，R 4，R 5，m和n具有权利要求书和描述中所述的含义，其互变异构体，其水合物及其药学上合适的盐。 在这些化合物中，优选其中R 1为任选取代的苯基-C 1 -C 2 - 烷基或杂芳基-C 1 -C 2烷基，R 2为任选取代的芳基，杂芳基，芳基-C 1 -C 6 - 烷基，芳基-C 2 -C 6 - 烯基 或杂芳基-C 1 -C 4 - 烷基，R 3是C 3 -C 4 - 烷基，C 1 -C 4 - 卤代烷基，C 2 -C 4 - 烯基，C 3 -C 6 - 环烷基，C 3 -C 6 - 环烷基-C 1 -C 2烷基，C 3 -C 6 - 杂环烷基-C 1 -C 2 - 烷基，苯基-C 1 -C 3 - 烷基，吡啶-2-基-C 1 -C 3 - 烷基或1,3-苯并恶唑-2-基 - 甲基，R 4和R 5彼此独立地是卤素 ，CF 3，CHF 2，CH 2 F，C 1 -C 2 - 烷基或C 1 -C 2 - 烷氧基，m和n彼此独立地为0或1。

公开(公告)号：US20120077840A1

公开(公告)日：2012-03-29

申请号：US13245123

申请日：2011-09-26

申请人： Sean Colm Turner ,  Margaretha Henrica Maria Bakker ,  Marcel Van Gaalen ,  Falko Ernst Wolter ,  Wilfried Hornberger ,  Marjoleen Nijsen

发明人： Sean Colm Turner ,  Margaretha Henrica Maria Bakker ,  Marcel Van Gaalen ,  Falko Ernst Wolter ,  Wilfried Hornberger ,  Marjoleen Nijsen

IPC分类号： A61K31/4709 ,  C07D471/04 ,  A61K31/437 ,  A61P25/28 ,  A61P25/18 ,  A61P27/06 ,  A61P25/16 ,  A61P25/02 ,  A61P27/02 ,  A61P19/02 ,  A61K31/4375 ,  C07D401/04 ,  A61P29/00

CPC分类号： C07D471/04 ,  C07D401/04

摘要： The present invention relates to novel heterocyclic compounds which are useful for inhibiting glycogen synthase kinase 3 (GSK-3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

摘要翻译： 本发明涉及可用于抑制糖原合酶激酶3（GSK-3），制备该化合物的方法，含该化合物的组合物和使用该化合物的治疗方法的新型杂环化合物。

公开(公告)号：US20110152325A1

公开(公告)日：2011-06-23

申请号：US12972679

申请日：2010-12-20

申请人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Möller ,  Wilfried Hornberger ,  Gisela Backfisch ,  Yanbin Lao ,  Marjoleen Nijsen

发明人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Möller ,  Wilfried Hornberger ,  Gisela Backfisch ,  Yanbin Lao ,  Marjoleen Nijsen

IPC分类号： A61K31/4439 ,  C07D401/04 ,  A61P25/28 ,  A61P25/00 ,  A61P25/08 ,  A61P25/04 ,  A61P13/12 ,  A61P35/00 ,  A61P31/18 ,  A61P37/02 ,  A61P33/06

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D413/14

摘要： The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity.The carboxamide compounds are compounds of the general formula I in which R1, R2, R3 R4, R5, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R1 is optionally substituted phenyl-C1-C2-alkyl or hetaryl-C1-C2-alkyl, R2 is optionally substituted aryl, hetaryl, aryl-C1-C6-alkyl, aryl-C2-C6-alkenyl or hetaryl-C1-C4-alkyl, R3 is C3-C4-alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C2-alkyl, C3-C6-heterocycloalkyl-C1-C2-alkyl, phenyl-C1-C3-alkyl, pyridin-2-yl-C1-C3-alkyl or 1,3-benzoxazol-2-yl-methyl, R4 and R5 independently of one another are halogen, CF3, CHF2, CH2F, C1-C2-alkyl or C1-C2-alkoxy, and m and n independently of one another are 0 or 1.

摘要翻译： 本发明涉及新的羧酰胺化合物及其用于制备药物的用途。 羧酰胺化合物是钙蛋白酶（钙依赖性半胱氨酸蛋白酶）的抑制剂。 因此，本发明还涉及这些羧酰胺化合物用于治疗与升高的钙蛋白酶活性相关的病症的用途。 羧酰胺化合物是通式I的化合物，其中R 1，R 2，R 3，R 4，R 5，m和n具有权利要求书和描述中所述的含义，其互变异构体，其水合物及其药学上合适的盐。 在这些化合物中，优选其中R 1为任选取代的苯基-C 1 -C 2 - 烷基或杂芳基-C 1 -C 2烷基，R 2为任选取代的芳基，杂芳基，芳基-C 1 -C 6 - 烷基，芳基-C 2 -C 6 - 烯基 或杂芳基-C 1 -C 4 - 烷基，R 3是C 3 -C 4 - 烷基，C 1 -C 4 - 卤代烷基，C 2 -C 4 - 烯基，C 3 -C 6 - 环烷基，C 3 -C 6 - 环烷基-C 1 -C 2烷基，C 3 -C 6 - 杂环烷基-C 1 -C 2 - 烷基，苯基-C 1 -C 3 - 烷基，吡啶-2-基-C 1 -C 3 - 烷基或1,3-苯并恶唑-2-基 - 甲基，R 4和R 5彼此独立地是卤素 ，CF 3，CHF 2，CH 2 F，C 1 -C 2 - 烷基或C 1 -C 2 - 烷氧基，m和n彼此独立地为0或1。

公开(公告)号：US09266855B2

公开(公告)日：2016-02-23

申请号：US13245123

申请日：2011-09-26

申请人： Sean Colm Turner ,  Margaretha Henrica Maria Bakker ,  Marcel Van Gaalen ,  Falko Ernst Wolter ,  Wilfried Hornberger ,  Marjoleen Nijsen

发明人： Sean Colm Turner ,  Margaretha Henrica Maria Bakker ,  Marcel Van Gaalen ,  Falko Ernst Wolter ,  Wilfried Hornberger ,  Marjoleen Nijsen

IPC分类号： C07D215/20 ,  A61K31/4709 ,  C07D401/04 ,  C07D471/04

CPC分类号： C07D471/04 ,  C07D401/04

摘要： The present invention relates to novel heterocyclic compounds which are useful for inhibiting glycogen synthase kinase 3 (GSK-3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

摘要翻译： 本发明涉及可用于抑制糖原合酶激酶3（GSK-3），制备该化合物的方法，含该化合物的组合物和使用该化合物的治疗方法的新型杂环化合物。

公开(公告)号：US20140005227A1

公开(公告)日：2014-01-02

申请号：US13992582

申请日：2011-12-08

申请人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Moller ,  Wilfried Hornberger ,  Yanbin Lao ,  Gisela Backfisch ,  Marjoleen Nijsen

发明人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Moller ,  Wilfried Hornberger ,  Yanbin Lao ,  Gisela Backfisch ,  Marjoleen Nijsen

IPC分类号： C07D401/04

CPC分类号： C07D401/04 ,  A61K31/4439 ,  C07D401/14 ,  Y02A50/411

摘要： The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R1, R2, R3, R4, X, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R1 is optionally substituted benzyl or hetaryl-methyl, X is a single bond or an oxygen atom, R2 is C1-C4-alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C2-alkyl, C3-C6-heterocycloalkyl-C1-C2-alkyl, phenyl, phenyl-C1-C3-alkyl, pyridin-2-yl-C1-C3-alkyl or CH2—C(O)OCH3, R3 and R4 independently of one another are halogen, CN, CF3, CHF2, CH2F, C1-C2-alkyl or C1-C2-alkoxy, and m and n independently of one another are 0 or 1.

摘要翻译： 本发明涉及新的羧酰胺化合物及其用于制备药物的用途。 羧酰胺化合物是钙蛋白酶（钙依赖性半胱氨酸蛋白酶）的抑制剂。 因此，本发明还涉及这些羧酰胺化合物用于治疗与升高的钙蛋白酶活性相关的病症的用途。 羧酰胺化合物是通式（I）的化合物，其中R 1，R 2，R 3，R 4，X，m和n具有权利要求书和描述中所述的含义，其互变异构体，其水合物和药学上合适的盐 其中。 在这些化合物中，优选其中R 1为任选取代的苄基或杂芳基 - 甲基，X为单键或氧原子，R 2为C 1 -C 4烷基，C 1 -C 4卤代烷基，C 2 -C 4 - 烯基，C 3 -C 6 环烷基，C 3 -C 6环烷基-C 1 -C 2烷基，C 3 -C 6杂环烷基-C 1 -C 2烷基，苯基，苯基-C 1 -C 3 - 烷基，吡啶-2-基-C 1 -C 3 - 烷基或CH 2 -C（O）OCH 3，R 3和R 4彼此独立地是卤素，CN，CF 3，CHF 2，CH 2 F，C 1 -C 2 - 烷基或C 1 -C 2 - 烷氧基，m和n彼此独立地为0或1。

公开(公告)号：US09062027B2

公开(公告)日：2015-06-23

申请号：US13992582

申请日：2011-12-08

申请人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Moller ,  Wilfried Hornberger ,  Yanbin Lao ,  Gisela Backfisch ,  Marjoleen Nijsen

发明人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Moller ,  Wilfried Hornberger ,  Yanbin Lao ,  Gisela Backfisch ,  Marjoleen Nijsen

IPC分类号： C07D401/14 ,  C07D401/04 ,  A61K31/4439 ,  A61P25/28

CPC分类号： C07D401/04 ,  A61K31/4439 ,  C07D401/14 ,  Y02A50/411

摘要： The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R1, R2, R3, R4, X, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R1 is optionally substituted benzyl or hetaryl-methyl, X is a single bond or an oxygen atom, R2 is C1-C4-alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C2-alkyl, C3-C6-heterocycloalkyl-C1-C2-alkyl, phenyl, phenyl-C1-C3-alkyl, pyridin-2-yl-C1-C3-alkyl or CH2—C(O)OCH3, R3 and R4 independently of one another are halogen, CN, CF3, CHF2, CH2F, C1-C2-alkyl or C1-C2-alkoxy, and m and n independently of one another are 0 or 1.

摘要翻译： 本发明涉及新的羧酰胺化合物及其用于制备药物的用途。 羧酰胺化合物是钙蛋白酶（钙依赖性半胱氨酸蛋白酶）的抑制剂。 因此，本发明还涉及这些羧酰胺化合物用于治疗与升高的钙蛋白酶活性相关的病症的用途。 羧酰胺化合物是通式（I）的化合物，其中R 1，R 2，R 3，R 4，X，m和n具有权利要求书和描述中所述的含义，其互变异构体，其水合物和药学上合适的盐 其中。 在这些化合物中，优选其中R 1为任选取代的苄基或杂芳基 - 甲基，X为单键或氧原子，R 2为C 1 -C 4烷基，C 1 -C 4卤代烷基，C 2 -C 4 - 烯基，C 3 -C 6 环烷基，C 3 -C 6环烷基-C 1 -C 2烷基，C 3 -C 6杂环烷基-C 1 -C 2烷基，苯基，苯基-C 1 -C 3 - 烷基，吡啶-2-基-C 1 -C 3 - 烷基或CH 2 -C（O）OCH 3，R 3和R 4彼此独立地是卤素，CN，CF 3，CHF 2，CH 2 F，C 1 -C 2 - 烷基或C 1 -C 2 - 烷氧基，m和n彼此独立地为0或1。

公开(公告)号：US09051304B2

公开(公告)日：2015-06-09

申请号：US12972663

申请日：2010-12-20

申请人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Möller ,  Wilfried Hornberger ,  Gisela Backfisch ,  Yanbin Lao ,  Marjoleen Nijsen

发明人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Möller ,  Wilfried Hornberger ,  Gisela Backfisch ,  Yanbin Lao ,  Marjoleen Nijsen

IPC分类号： C07D401/04 ,  C07D401/14 ,  C07D207/28 ,  C07D409/14 ,  C07D417/14

CPC分类号： C07D401/04 ,  C07D207/28 ,  C07D401/14 ,  C07D409/14 ,  C07D417/14

摘要： The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity.The carboxamide compounds are compounds of the general formula I in which R1, R2, R3 R4, R5, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R1 is optionally substituted phenyl-C1-C2-alkyl or hetaryl-C1-C2-alkyl, R2 is optionally substituted aryl, hetaryl, aryl-C1-C6-alkyl, aryl-C2-C6-alkenyl or hetaryl-C1-C4-alkyl, R3 is C1-C3-alkyl, C1-C3-haloalkyl, C2-C4-alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C2-alkyl, or phenyl-C1-C3-alkyl, R4 and R5 independently of one another are halogen, CF3, CHF2, CH2F, C1-C2-alkyl or C1-C2-alkoxy, and m and n independently of one another are 0 or 1.

摘要翻译： 本发明涉及新的羧酰胺化合物及其用于制备药物的用途。 羧酰胺化合物是钙蛋白酶（钙依赖性半胱氨酸蛋白酶）的抑制剂。 因此，本发明还涉及这些羧酰胺化合物用于治疗与升高的钙蛋白酶活性相关的病症的用途。 羧酰胺化合物是通式I的化合物，其中R 1，R 2，R 3，R 4，R 5，m和n具有权利要求书和描述中所述的含义，其互变异构体，其水合物及其药学上合适的盐。 在这些化合物中，优选其中R 1为任选取代的苯基-C 1 -C 2烷基或杂芳基-C 1 -C 2烷基，R 2为任选取代的芳基，杂芳基，芳基-C 1 -C 6 - 烷基，芳基-C 2 -C 6 - 烯基 或杂芳基-C 1 -C 4 - 烷基，R 3是C 1 -C 3 - 烷基，C 1 -C 3 - 卤代烷基，C 2 -C 4 - 烯基，C 3 -C 6 - 环烷基，C 3 -C 6 - 环烷基-C 1 -C 2烷基或苯基 - C 1 -C 3 - 烷基，R 4和R 5彼此独立地是卤素，CF 3，CHF 2，CH 2 F，C 1 -C 2 - 烷基或C 1 -C 2 - 烷氧基，m和n彼此独立地为0或1。

公开(公告)号：US20110152265A1

公开(公告)日：2011-06-23

申请号：US12972663

申请日：2010-12-20

申请人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Möller ,  Wilfried Hornberger ,  Gisela Backfisch ,  Yanbin Lao ,  Marjoleen Nijsen

发明人： Andreas Kling ,  Katja Jantos ,  Helmut Mack ,  Achim Möller ,  Wilfried Hornberger ,  Gisela Backfisch ,  Yanbin Lao ,  Marjoleen Nijsen

IPC分类号： A61K31/5355 ,  C07D401/04 ,  A61K31/4439 ,  A61P25/28 ,  A61P25/16 ,  A61P25/08 ,  A61P9/00 ,  A61P13/12 ,  A61P31/18 ,  A61P33/06 ,  C07D413/14

CPC分类号： C07D401/04 ,  C07D207/28 ,  C07D401/14 ,  C07D409/14 ,  C07D417/14

摘要： The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity.The carboxamide compounds are compounds of the general formula I in which R1, R2, R3 R4, R5, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R1 is optionally substituted phenyl-C1-C2-alkyl or hetaryl-C1-C2-alkyl, R2 is optionally substituted aryl, hetaryl, aryl-C1-C6-alkyl, aryl-C2-C6-alkenyl or hetaryl-C1-C4-alkyl, R3 is C1-C3-alkyl, C1-C3-haloalkyl, C2-C4-alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C2-alkyl, or phenyl-C1-C3-alkyl, R4 and R5 independently of one another are halogen, CF3, CHF2, CH2F, C1-C2-alkyl or C1-C2-alkoxy, and m and n independently of one another are 0 or 1.

摘要翻译： 本发明涉及新的羧酰胺化合物及其用于制备药物的用途。 羧酰胺化合物是钙蛋白酶（钙依赖性半胱氨酸蛋白酶）的抑制剂。 因此，本发明还涉及这些羧酰胺化合物用于治疗与升高的钙蛋白酶活性相关的病症的用途。 羧酰胺化合物是通式I的化合物，其中R 1，R 2，R 3，R 4，R 5，m和n具有权利要求书和描述中所述的含义，其互变异构体，其水合物及其药学上合适的盐。 在这些化合物中，优选其中R 1为任选取代的苯基-C 1 -C 2 - 烷基或杂芳基-C 1 -C 2烷基，R 2为任选取代的芳基，杂芳基，芳基-C 1 -C 6 - 烷基，芳基-C 2 -C 6 - 烯基 或杂芳基-C 1 -C 4 - 烷基，R 3是C 1 -C 3 - 烷基，C 1 -C 3 - 卤代烷基，C 2 -C 4 - 烯基，C 3 -C 6 - 环烷基，C 3 -C 6 - 环烷基-C 1 -C 2烷基或苯基 - C 1 -C 3 - 烷基，R 4和R 5彼此独立地是卤素，CF 3，CHF 2，CH 2 F，C 1 -C 2 - 烷基或C 1 -C 2 - 烷氧基，m和n彼此独立地为0或1。