- 专利标题: Carboxamide compounds and their use as calpain inhibitors
-
申请号: US12810795申请日: 2008-12-29
-
公开(公告)号: US09150553B2公开(公告)日: 2015-10-06
- 发明人: Wilfried Hornberger , Helmut Mack , Andreas Kling , Achim Moeller , Barbara Vogg , Jürgen Delzer , Gisela Backfisch , Armin Beyerbach
- 申请人: Wilfried Hornberger , Helmut Mack , Andreas Kling , Achim Moeller , Barbara Vogg , Jürgen Delzer , Gisela Backfisch , Armin Beyerbach
- 申请人地址: DE Wiesbaden
- 专利权人: AbbVie Deutschland GmbH & Co. KG
- 当前专利权人: AbbVie Deutschland GmbH & Co. KG
- 当前专利权人地址: DE Wiesbaden
- 代理机构: Michael Best & Friedrich LLP
- 代理商 Lisa V. Mueller
- 优先权: WOPCT/EP2007/064617 20071228; EP08159041 20080625
- 国际申请: PCT/EP2008/068313 WO 20081229
- 国际公布: WO2009/083581 WO 20090709
- 主分类号: C07D405/14
- IPC分类号: C07D405/14 ; A61K31/4439 ; 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/授权文献
信息查询