公开(公告)号：US06380220B1

公开(公告)日：2002-04-30

申请号：US09284543

申请日：1999-04-15

申请人： Wilfried Lubisch ,  Achim Möller ,  Jürgen Delzer

发明人： Wilfried Lubisch ,  Achim Möller ,  Jürgen Delzer

IPC分类号： A61K31445

CPC分类号： C07D401/06 ,  C07D211/62 ,  C07D401/12

摘要： Piperidineketocarboxylic acid derivatives of the general formula I and their tautomeric and isomeric forms, and physiologically tolerable salts thereof, where the variables have the meanings given in the description, preparation of these compounds and their use as drugs.

摘要翻译： 通式I的哌啶酮羧酸衍生物及其互变异构体和异构体形式及其生理上可耐受的盐，其中变量具有说明书中给出的含义，这些化合物的制备及其作为药物的用途。

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：US20110059968A1

公开(公告)日：2011-03-10

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： A61K31/5377 ,  C07D405/12 ,  A61K31/465 ,  C07D413/14 ,  C07D401/14 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/444 ,  A61K31/4439 ,  A61P25/00 ,  A61P9/00 ,  A61P19/00 ,  A61P21/00 ,  A61P27/02

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, COON, 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.