公开(公告)号：US5863509A

公开(公告)日：1999-01-26

申请号：US94501

申请日：1998-06-10

申请人： Burkhard Standke ,  Roland Edelmann ,  Albert-Johannes Frings ,  Ralf Laven ,  Michael Horn ,  Peter Jenkner ,  Helmut Mack ,  Jaroslaw Monkiewicz

发明人： Burkhard Standke ,  Roland Edelmann ,  Albert-Johannes Frings ,  Ralf Laven ,  Michael Horn ,  Peter Jenkner ,  Helmut Mack ,  Jaroslaw Monkiewicz

IPC分类号： C09K3/00 ,  C03C17/30 ,  C03C25/40 ,  C04B41/49 ,  C08G77/22 ,  C08G77/24 ,  C08G77/26 ,  C08L83/08 ,  C09D5/00 ,  C09D183/08 ,  C09K3/18 ,  C14C9/00 ,  C23C30/00 ,  D06M15/657 ,  B05D7/00

CPC分类号： C14C9/00 ,  C03C17/30 ,  C03C25/40 ,  C04B41/4961 ,  C08G77/22 ,  C08G77/24 ,  C08G77/26 ,  C09D183/08 ,  C09K3/18 ,  C23C30/00 ,  D06M15/657 ,  C23C2222/20 ,  D06M2101/06 ,  D06M2200/11 ,  D06M2200/12 ,  Y10T428/31663

摘要： An aqueous alcoholic fluoroalkyl functional group containing organopolysiloxane-composition, comprising:organopolysiloxanes of formula I:RO�Si(A)(CH.sub.3).sub.z (OR).sub.1-z O!.sub.a �Si(B)(R.sup.2).sub.y (OR).sub.1-y O!.sub.b �Si(C)(CH.sub.3)O!.sub.c �Si(D)(OR)O!.sub.d R.multidot.(HX) (I)wherein A is an aminoalkyl radical derived from the compound of formula II:H.sub.2 N(CH.sub.2).sub.f (NH).sub.g (CH.sub.2).sub.h Si(OR).sub.3-z (CH.sub.3).sub.z (II)wherein 0.ltoreq.f.ltoreq.6, 9=0 if f=0 and g=1 if f>0, 0.ltoreq.h.ltoreq.6 and 0.ltoreq.z.ltoreq.1, and B is a fluoroalkyl radical derived from the compound of formula III:R.sup.1 --Y--(CH.sub.2).sub.2 Si(R.sup.2).sub.y (OR).sub.3-y (III)wherein R.sup.1 is a mono-, oligo- or perfluorinated alkyl group having 1-9 C atoms or a mono-, oligo- or perfluorinated aryl group, Y is a CH.sub.2, O or S group, R.sub.2 is a linear, branched or cyclic alkyl group having 1-8 C atoms or an aryl group and 0.ltoreq.y.ltoreq.1, and C is an alkyl radical derived from the compound of formula IV:R.sup.3 --Si(CH.sub.3)(OR).sub.2 (IV)and D is also an alkyl radical derived from the compound of formula V:R.sup.3 --Si(OR).sub.3 (V)wherein R.sup.3 in the preceding formulae is in each case identical or different, and is a linear, branched or cyclic alkyl group having 1-8 C atoms, R in the preceding formulae is in each case identical or different, and is a linear, branched or cyclic alkyl group having 1-8 C atoms or an aryl group, and HX is an acid, in which X is an inorganic or organic acid radical, and 0.ltoreq.y.ltoreq.1, 0.ltoreq.z.ltoreq.1, a>0, b>0, c.gtoreq.0, d.gtoreq.0, e.gtoreq.0 and (a+b+c+d).gtoreq.2.

摘要翻译： 含有有机聚硅氧烷组合物的含水醇氟代烷基官能团包括：式I的有机聚硅氧烷：RO [Si（A）（CH3）z（OR）1-zO] a [Si（B）（R2）y（OR） yO] b [Si（C）（CH3）O] c [Si（D）（OR）O] dRx（HX）（I）其中A是衍生自式II化合物的氨基烷基：H 2 N（CH 2）f （NH）g（CH 2）h Si（OR）3-z（CH 3）z（II）其中0 0，则g = R =（Y） - （CH 2）2 Si（R 2）y（OR）3-y （III）其中R1是具有1-9个C原子的单，低聚或全氟烷基或单，低聚或全氟化的芳基，Y是CH 2，O或S基团，R 2是直链，支链 或具有1-8个碳原子或芳基且0≤y≤1的环状烷基，C是衍生自式IV化合物的烷基：R3-Si（CH3）（OR）2（ IV），D也是衍生自式V化合物的烷基：R3-Si（OR）3（V）其中前述通式中的R 3在每种情况下均为 或具有1-8个C原子的直链，支链或环状烷基，前述式中的R各自相同或不同，为具有1-8个C原子的直链，支链或环状烷基 或芳基，并且HX是酸，其中X是无机或有机酸基团，并且0≤y≤1,0≤z≤1，a> 0，b> 0 ，c> / = 0，d> / = 0，e> / = 0和（a + b + c + d）> / = 2。

公开(公告)号：US09382383B2

公开(公告)日：2016-07-05

申请号：US14358437

申请日：2012-10-30

申请人： Spomenko Ljesic ,  Christopher Studte ,  Helmut Mack

发明人： Spomenko Ljesic ,  Christopher Studte ,  Helmut Mack

IPC分类号： C07F7/04 ,  C08G77/16 ,  C04B24/42 ,  C08G77/42 ,  C08L83/10 ,  C08G77/06 ,  C04B28/14 ,  C04B103/00 ,  C04B103/65 ,  C04B111/27

CPC分类号： C08G77/16 ,  C04B24/42 ,  C04B28/14 ,  C04B2103/0061 ,  C04B2103/65 ,  C04B2111/27 ,  C08G77/06 ,  C08G77/42 ,  C08L83/10

摘要： The invention relates to a composition and a method for the production of the composition comprising block cocondensates of propylfunctional alkaline siliconates and silicates.

摘要翻译： 本发明涉及一种组合物和制备该组合物的方法，该组合物包含丙基官能的碱性硅酸盐和硅酸盐的嵌段共缩合物。

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：US20140045969A1

公开(公告)日：2014-02-13

申请号：US13989157

申请日：2011-11-25

申请人： Simone Klapdohr ,  Jochen Mezger ,  Burkhard Walther ,  Helmut Mack

发明人： Simone Klapdohr ,  Jochen Mezger ,  Burkhard Walther ,  Helmut Mack

IPC分类号： C09J11/06

CPC分类号： C09J11/06 ,  C08K3/38 ,  C08K5/17 ,  C08K5/55 ,  C09D201/10

摘要： The invention relates to a composition comprising (A) at least 5% by weight of en organic prepolymer P having at least two water-crossilnkable organosilicon end groups, (B) 0.01% to 3.0% by weight of boric acid and/or bone ester, and (C) 0.01% to 3.0% by weight of an amine component. Additionally disclosed is a method for the curing of these compositions and also the use of boric acid and/or boric esters and an amine component a condensation catalyst.

摘要翻译： 本发明涉及一种组合物，其包含（A）至少5重量％的具有至少两个可水解的有机硅端基的有机预聚物P，（B）0.01重量％至3.0重量％的硼酸和/或骨酯 ，（C）0.01〜3.0重量％的胺成分。 另外公开了这些组合物的固化方法，以及使用硼酸和/或硼酸酯和胺组分的缩合催化剂。

公开(公告)号：US08536251B2

公开(公告)日：2013-09-17

申请号：US13132990

申请日：2009-11-25

申请人： Silke Flakus ,  Klaus Lorenz ,  Helmut Mack ,  Christian Scholz ,  Petra Wagner ,  Barbara Wimmer ,  Angelika Hartl ,  Martin Winklbauer ,  Manfred Bichler

发明人： Silke Flakus ,  Klaus Lorenz ,  Helmut Mack ,  Christian Scholz ,  Petra Wagner ,  Barbara Wimmer ,  Angelika Hartl ,  Martin Winklbauer ,  Manfred Bichler

IPC分类号： C04B24/26 ,  C08L53/00 ,  C08L39/04 ,  C08L27/04 ,  C08L29/00 ,  C08K5/00 ,  C08F16/12 ,  C08F220/12 ,  C08F12/30 ,  C08F30/02

CPC分类号： C08F216/1416 ,  C04B24/2605 ,  C04B24/2647 ,  C04B24/267 ,  C04B28/02 ,  C04B28/04 ,  C04B2103/30 ,  C04B2103/408 ,  C08F220/06 ,  C04B14/06

摘要： The invention relates to a copolymer comprising i) 3 to 40 mol % of an isoprenolpolyether derivative structural unit α ii) 3 to 40 mol % of a vinyloxypolyether derivative structural unit β and iii) 35 to 93 mol % of an acid structural unit γ, the structural units of the copolymer which belong to the vinyloxypolyether derivative structural unit β having longer side chains than the structural units which belong to the isoprenolpolyether derivative structural unit α.

摘要翻译： 本发明涉及一种共聚物，其包含i）3至40mol％的异戊二烯聚醚衍生物结构单元αii）3至40mol％的乙烯氧基聚醚衍生物结构单元β和iii）35至93mol％的酸性结构单元γ， 属于乙烯氧基聚醚醚衍生物结构单元β的共聚物的结构单元具有比属于异戊二烯聚醚衍生物结构单元α的结构单元更长的侧链。

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。