公开(公告)号：US08283363B2

公开(公告)日：2012-10-09

申请号：US12940339

申请日：2010-11-05

申请人： Helmut Mack ,  Andreas Kling ,  Katja Jantos ,  Achim Moeller ,  Wilfried Hornberger ,  Charles W. Hutchins

发明人： Helmut Mack ,  Andreas Kling ,  Katja Jantos ,  Achim Moeller ,  Wilfried Hornberger ,  Charles W. Hutchins

IPC分类号： A61P35/00 ,  A61P25/00 ,  A61P29/00 ,  A61P31/00 ,  A61P9/00 ,  A61P27/02 ,  A61K31/425 ,  A61K31/451 ,  A61K31/4015 ,  A61K31/4439 ,  A61K31/4164 ,  C07D211/40 ,  C07D207/12 ,  C07D401/02 ,  C07D233/02 ,  C07D275/03

CPC分类号： C07D207/22 ,  C07D207/26 ,  C07D207/28 ,  C07D211/76 ,  C07D211/78 ,  C07D213/81 ,  C07D233/32 ,  C07D233/34 ,  C07D239/10 ,  C07D275/03 ,  C07D401/06 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12

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, R3a, R3b, R4, Q, Y, A and X have the meanings mentioned in the claims and the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula Ia and Ib in which R1, r, R2b, R3a, R3b, R4, Y and X have the meanings mentioned in the claims, including the tautomers thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein Y is a moiety CH2—CH2, CH2—CH2—CH2, N(Ry#)—CH2, N(Ry#)—CH2—CH2 or CH═CH—CH═, each optionally having 1 or 2 H-atoms replaced with identical or different radicals Ry, wherein Ry and Ry# have the meanings mentioned in the claims.

公开(公告)号：US07491729B2

公开(公告)日：2009-02-17

申请号：US10539708

申请日：2003-12-17

申请人： Margaretha Bakker ,  Wilfried Hornberger ,  Andreas Kling ,  Udo Lange ,  Helmut Mack ,  Achim Moeller ,  Reinhold Mueller ,  Kurt Schellhaas ,  Martin Schmidt ,  Gerd Steiner ,  Karsten Wicke

发明人： Margaretha Bakker ,  Wilfried Hornberger ,  Andreas Kling ,  Udo Lange ,  Helmut Mack ,  Achim Moeller ,  Reinhold Mueller ,  Kurt Schellhaas ,  Martin Schmidt ,  Gerd Steiner ,  Karsten Wicke

IPC分类号： A01N43/54 ,  A61K31/505 ,  C07D239/00 ,  C07D471/00 ,  C07D487/00 ,  C07D491/00

CPC分类号： C07D495/14

摘要： 3-Substituted 3,4-dihydrothieno[2,3-d]pyrimidin-4-one derivatives, production and use thereof. The invention relates to 3,4-dihydrothieno[2,3-d]pyrimidin-4-one derivatives which are substituted in position 3 by 5-membered heteroaryl which may be fused to an aryl or heteroaryl radical, where the heteroaryl and, if appropriate, the fused aryl or heteroaryl radical may have 1, 2 or 3 substituents selected independently of one another from C1-5-alkyl, C1-5-alkoxy, C1-5-alkylthio, halogen, CN, halo-C1-5-alkyl, halo-C1-5-alkoxy, hydroxy, —NH2, —N(R6)2, —NH(R6), aryl, aryloxy, aralkyl, aralkyloxy and heteroaryl, where the substituents aryl, aryloxy, aralkyl, aralkyloxy and heteroaryl may have 1, 2 or 3 substituents selected independently of one another from C1-5-alkyl, C1-5-alkoxy, C1-5-alkylthio, halogen, CN, halo-C1-5-alkyl, halo-C1-5-alkoxy, hydroxy, —NH2, —N(R6)2 and —NH(R6). The preparation and use of these derivatives, especially for therapeutic purposes, e.g. for the treatment of depressions, are likewise described.

摘要翻译： 3-取代的3,4-二氢噻吩并[2,3-d]嘧啶-4-酮衍生物，的制备和用途。 本发明涉及在3位被5位杂芳基取代的3,4-二氢噻吩并[2,3-d]嘧啶-4-酮衍生物，其可以与芳基或杂芳基稠合，其中杂芳基和 稠合的芳基或杂芳基可以具有1,2或3个彼此独立地选自C 1-5 - 烷基，C 1-5 - 烷氧基，C 1-5 - 烷硫基，卤素，CN，卤代-C 1-5 - 烷基，卤代C 1-5 - 烷氧基，羟基，-NH 2，-N（R 6）2，-NH（R 6），芳基，芳氧基，芳烷基，芳烷氧基和杂芳基，其中芳基，芳氧基，芳烷基，芳烷氧基和杂芳基 可以具有1,2或3个彼此独立地选自C 1-5 - 烷基，C 1-5 - 烷氧基，C 1-5 - 烷硫基，卤素，CN，卤代C 1-5 - 烷基，卤代-C 1-5 - 烷氧基，羟基，-NH 2，-N（R 6）2和-NH（R 6）。 这些衍生物的制备和使用，特别是用于治疗目的，例如 为了处理凹陷，同样地描述。

公开(公告)号：US20080234329A1

公开(公告)日：2008-09-25

申请号：US12070941

申请日：2008-02-22

申请人： Andreas Kling ,  Wilfried Hornberger ,  Helmut Mack ,  Achim Moeller ,  Volker Nimmrich ,  Dietmar Seemann ,  Wilfried Lubisch

发明人： Andreas Kling ,  Wilfried Hornberger ,  Helmut Mack ,  Achim Moeller ,  Volker Nimmrich ,  Dietmar Seemann ,  Wilfried Lubisch

IPC分类号： A61K31/4439 ,  C07D401/00

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D491/048 ,  C07D493/04 ,  C07D513/04

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, R3a, R3b, W, Y and X have the meanings mentioned in the claims and the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula I-A.a′ and I-A.a″ in which m, E, R1, R3a, R3b, R2, Ry, Rw and Rw6* have the meanings mentioned in the claims, n is 0, 1 or 2, the tautomers thereof and the pharmaceutically suitable salts thereof.

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 3，R 3， >，W，Y和X具有权利要求书和说明书中所述的含义，其互变异构体及其药学上合适的盐。 特别地，化合物具有通式IA.a'和IA.a“，其中m，E，R 1，R 3a，R 3b， R 2，R 2，R 2，W 2和R 6具有如下的含义： 权利要求书，n为0,1或2，其互变异构体及其药学上合适的盐。

公开(公告)号：US09150553B2

公开(公告)日：2015-10-06

申请号：US12810795

申请日：2008-12-29

申请人： Wilfried Hornberger ,  Helmut Mack ,  Andreas Kling ,  Achim Moeller ,  Barbara Vogg ,  Jürgen Delzer ,  Gisela Backfisch ,  Armin Beyerbach

发明人： Wilfried Hornberger ,  Helmut Mack ,  Andreas Kling ,  Achim Moeller ,  Barbara Vogg ,  Jürgen Delzer ,  Gisela Backfisch ,  Armin Beyerbach

IPC分类号： C07D405/14 ,  A61K31/4439 ,  C07D491/052

CPC分类号： C07D405/14 ,  C07D491/052

摘要： The present invention relates to novel carboxamide compounds of the formula I and their use for the manufacture of a medicament. The carboxamide compounds are prodrugs of 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. R1 is C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C4-alkyl, aryl, hetaryl, aryl-C1-C6-alkyl, aryl-C2-C6-alkenyl, hetaryl-C1-C4-alkyl or hetaryl-C2-C6-alkenyl, R2 is C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C4-alkyl, aryl, O-aryl, O—CH2-aryl, hetaryl, aryl-C1-C6-alkyl, aryl-C2-C6-alkenyl, hetaryl-C1-C4-alkyl or hetaryl-C2-C6-alkenyl, R3a and R3b together form a moiety S-Alk-S, O-Alk-S or O-Alk-O, wherein Alk is linear C2-C5-alkandiyl, which may be unsubstituted or substituted with 1, 2, 3 or 4 radicals selected from C1-C4-alkyl or halogen; X is a radical of the formulae C(═O)—O—Rx1, C(═O)—NRx2Rx3, C(═O)—N(Rx4)—(C1-C6-alkylene)-NRx2Rx3, C(═O)—N(Rx4)NRx2Rx3, n is 0, 1 or 2, one of the variables Y1, Y2, Y3 or Y4 is a nitrogen atom, and the remaining variables Y1, Y2, Y3 or Y4 are CH; Ry is e.g. OH, SH, halogen, NO2, NH2, CN, CF3, CHF2, CH2F, O—CF3, O—CHF2, O—CH2F, COOH, OCH2COOH, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkoxy-C1-C4-alkyl, C1-C6-alkylthio etc. W is a radical of the formulae W1 or W2 which is linked via nitrogen: in which * means the linkage to the 6-membered heteroaromatic ring, and # means the linkage to R2, m is 0, 1 or 2, and Rw is e.g. OH, SH, halogen, NO2, NH2, CN, CF3, CHF2, CH2F, O—CF3, O—CHF2, O—CH2F, COOH, OCH2COOH.

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：US08906941B2

公开(公告)日：2014-12-09

申请号：US12708662

申请日：2010-02-19

申请人： Andreas Kling ,  Helmut Mack ,  Katja Jantos ,  Achim Moeller ,  Wilfried Hornberger ,  Charles W. Hutchins

发明人： Andreas Kling ,  Helmut Mack ,  Katja Jantos ,  Achim Moeller ,  Wilfried Hornberger ,  Charles W. Hutchins

IPC分类号： C07D277/30 ,  C07D417/04 ,  C07D417/02 ,  C07D413/04 ,  C07D401/04 ,  C07D401/02 ,  A61K31/4439 ,  A61P25/28

CPC分类号： C07D417/04 ,  C07D277/30 ,  C07D401/04 ,  C07D413/04

摘要： The present invention relates to novel carboxamide compounds and their use as 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 and to a method for the therapeutic and/or prophylactic treatment by administering an effective amount of at least one of these carboxamide compounds.The carboxamide compounds are compounds of the general formula I in which W—R2 is selected from and R1, R2, R3a, R3b, Y1, Y2, Y3, Y4, X, Q, m, k, Rw and Rw* have the meanings mentioned in the claims, the tautomers thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein Y1, Y2, Y3 and Y4 are CRy, or one or two of the variables Y1 to Y4 are a nitrogen atom and the remaining variables are CRy, wherein the radicals Ry may be identical or different and have the meanings mentionend in the claims.

摘要翻译： 本发明涉及新的羧酰胺化合物及其作为药物的用途。 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钙蛋白酶活性升高相关的疾病的用途，以及通过施用有效量的这些羧酰胺化合物中的至少一种来进行治疗和/或预防性治疗的方法。 羧酰胺化合物是其中W-R2选自并且R 1，R 2，R 3a，R 3b，Y 1，Y 2，Y 3，Y 4，X，Q，m，k，Rw和Rw *具有通式I的化合物 权利要求中提及的其互变异构体及其药学上合适的盐。 在这些化合物中，优选其中Y1，Y2，Y3和Y4为CRy，或变量Y1至Y4中的一个或两个为氮原子，剩余的变量为CRy，其中基团Ry可以相同或不同，并且具有 意思是在权利要求中提及。

公开(公告)号：US08445686B2

公开(公告)日：2013-05-21

申请号：US12675430

申请日：2008-08-26

申请人： Helmut Mack ,  Nicole Teusch ,  Bernhard K. Mueller ,  Wilfried Hornberger ,  Michael F. Jarvis ,  Daryl Sauer ,  Steve Swann, Jr. ,  Dominique Bonafoux ,  Ryan Keddy ,  Adrian Donald Hobson ,  Anil Vasudevan

发明人： Helmut Mack ,  Nicole Teusch ,  Bernhard K. Mueller ,  Wilfried Hornberger ,  Michael F. Jarvis ,  Daryl Sauer ,  Steve Swann, Jr. ,  Dominique Bonafoux ,  Ryan Keddy ,  Adrian Donald Hobson ,  Anil Vasudevan

IPC分类号： C07D211/78 ,  C07D211/72 ,  C07D211/84 ,  A61K31/44

CPC分类号： C07D401/12 ,  C07D213/56 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

摘要： The present invention relates to novel 4-(4-pyridyl)-benzamides of the formula (I). The compounds I possess valuable therapeutic properties and are suitable, in particular, for treating diseases that respond to modulation of Rho kinases (ROCKs). R1 and R2 are, independently of each other, hydrogen, hydroxy, cyano, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-alkoxy or C1-C8-haloalkoxy; R3, R4, R5 and R6 are, independently of each other, hydrogen, hydroxy, halogen, cyano, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-alkoxy, C1-C8-haloalkoxy, amino, C1-C8-alkylamino or di-(C1-C8-alkyl)-amino; R7 is hydrogen, C1-C8-alkyl, C1-C8-haloalkyl, aryl or aryl-C1-C8-alkyl; R8 is a group of the formula —X—W, where X is a single bond, C1-C4-alkylene or C1-C4-alkylene-O—, where the alkylene group in the three last-mentioned radicals may be linear or branched and may be partly or fully halogenated and/or may be substituted by a hydroxyl group and/or may be interrupted by an oxygen atom; and W is a cyclic radical selected from phenyl and a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which contains as ring members 1, 2 or 3 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups; R9 is a group of the formula —Y—Z, where Z is hydrogen, halogen, OR11, NR12R13, S(O)m—R14, phenyl which may carry 1, 2, 3 or 4 substituents R15 or a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring; and Y is linear or branched C1C4-alkylene which may be partly or fully halogenated and/or may be substituted by a hydroxyl group and/or a phenyl ring; or, in case Z is phenyl or the 5- or 6-membered heterocyclic ring as defined above, Y can also be a single bond.

摘要翻译： 本发明涉及式（I）的新型4-（4-吡啶基） - 苯甲酰胺。 化合物I具有有价值的治疗特性，特别适用于治疗对Rho激酶（ROCK）的调节作用的疾病。 R 1和R 2彼此独立地为氢，羟基，氰基，C 1 -C 8 - 烷基，C 1 -C 8 - 卤代烷基，C 1 -C 8 - 烷氧基或C 1 -C 8 - 卤代烷氧基; R3，R4，R5和R6彼此独立地为氢，羟基，卤素，氰基，C1-C8-烷基，C1-C8-卤代烷基，C1-C8-烷氧基，C1-C8-卤代烷氧基，氨基，C1- C 8 - 烷基氨基或二 - （C 1 -C 8 - 烷基） - 氨基; R 7是氢，C 1 -C 8 - 烷基，C 1 -C 8 - 卤代烷基，芳基或芳基-C 1 -C 8 - 烷基; R8是式-XW的基团，其中X是单键，C1-C4-亚烷基或C1-C4-亚烷基-O-，其中三个最后提及的基团中的亚烷基可以是直链或支链的，并且可以 部分或完全卤化和/或可以被羟基取代和/或可被氧原子中断; 并且W是选自苯基和5-或6-元饱和，部分不饱和或芳族杂环的环状基团，其含有作为环成员1,2或3的选自O，S和N的杂原子以及任选的1或2个羰基 ; R9是式-YZ的基团，其中Z是氢，卤素，OR11，NR12R13，S（O）m -R14，可以带有1,2,3或4个取代基R15或5-或6-元的苯基 饱和，部分不饱和或芳族杂环; Y是可部分或完全卤化和/或可被羟基和/或苯环取代的直链或支链C 1 -C 4亚烷基; 或者Z为苯基或上述5-或6-元杂环的情况下，Y也可以是单键。

公开(公告)号：US08436034B2

公开(公告)日：2013-05-07

申请号：US11990652

申请日：2007-12-28

申请人： Andreas Kling ,  Wilfried Hornberger ,  Helmut Mack ,  Achim Moeller ,  Volker Nimmrich ,  Dietmar Seeman ,  Wilfried Lubisch

发明人： Andreas Kling ,  Wilfried Hornberger ,  Helmut Mack ,  Achim Moeller ,  Volker Nimmrich ,  Dietmar Seeman ,  Wilfried Lubisch

IPC分类号： A61K31/4155 ,  A61K31/4178 ,  C07D403/04

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D491/048 ,  C07D493/04 ,  C07D513/04

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, R3a, R3b, W, Y and X have the meanings mentioned in the claims and the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula I-A.a′ and I-A.a″ in which m, E, R1, R3a, R3b, R2, Ry, Rw and Rw6* have the meanings mentioned in the claims, n is 0, 1 or 2, the tautomers thereof and the pharmaceutically suitable salts thereof.

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R1，R2，R3a，R3b，W，Y和X具有权利要求书和说明书中所述的含义，其互变异构体及其药学上合适的盐。 特别地，化合物具有通式IA.a'和IA.a“，其中m，E，R1，R3a，R3b，R2，Ry，Rw和Rw6 *具有权利要求中提及的含义，n为0 ，1或2，其互变异构体及其药学上合适的盐。

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。