公开(公告)号：US20110275615A1

公开(公告)日：2011-11-10

申请号：US12915680

申请日：2010-10-29

申请人： Hans-Jörg Treiber ,  Monika Knopp ,  Wilfried Lubisch ,  Achim Moeller

发明人： Hans-Jörg Treiber ,  Monika Knopp ,  Wilfried Lubisch ,  Achim Moeller

IPC分类号： A61K31/166 ,  C07D213/80 ,  C07D295/135 ,  C07D207/09 ,  C07D211/32 ,  C07D213/50 ,  C07D401/10 ,  C07D413/10 ,  C07D209/14 ,  C07D223/04 ,  C07D217/20 ,  A61K31/455 ,  A61K31/5375 ,  A61K31/40 ,  A61K31/495 ,  A61K31/4453 ,  A61K31/44 ,  A61K31/496 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/5377 ,  A61K31/454 ,  A61K31/55 ,  A61K31/4725 ,  A61K31/472 ,  A61P25/28 ,  A61P25/00 ,  A61P25/14 ,  A61P25/08 ,  A61P9/10 ,  A61P21/00 ,  A61P35/00 ,  A61P9/00 ,  A61P27/12 ,  A61P35/04 ,  A61P29/00 ,  C07C237/32

CPC分类号： C07D213/82 ,  A61K31/195 ,  A61K31/5375 ,  C07C229/38 ,  C07C237/22 ,  C07C237/32 ,  C07C2601/14 ,  C07D295/155

摘要： An amide of the formula I and its tautomeric forms, possible enantiomeric and diastereomeric forms, E and Z forms, and possible physiologically tolerated salts, in which the variables have the following meanings: A —(CH2)p—R1, where R1 can be pyrrolidine, morpholine, piperidine, —NR5R6 and and R5, R6 and R7 can, independently of one another, be hydrogen, C1-C4-alkyl, CH2Ph, Ph, CH2CH2Ph, it also being possible for the phenyl rings to be substituted by R6, and p can be 1 and 2, and B can be phenyl, pyridyl, pyrimidyl and pyridazyl, it also being possible for the rings to be substituted by up to 2 R8 radicals, and D can be a bond, —(CH2)m—, —CH═CH—, —C═C—, and R2 is chlorine, bromine, fluorine, C1-C6-alkyl, NHCO—C1-C4-alkyl, NHSO2—C1-C4-alkyl, NO2, —O—C1-C4-alkyl and NH2, and R3 is —C1-C6-alkyl, branched or unbranched, and which may also carry a phenyl ring, indolyl ring or cyclohexyl ring which is in turn substituted by a maximum of two R8 radicals, where R8 is hydrogen, C1-C4-alkyl, branched or unbranched, —O—C1-C4-alkyl, OH, Cl, F, Br, I, CF3, NO2, NH2, CN, COOH, COO—C1-C4-alkyl, NHCO—C1-C4-alkyl, —NHSO2—C1-C4-alkyl and —SO2—C1-C4-alkyl; and Y is phenyl, pyridine, pyrimidine and pyrazine and R4 is hydrogen, COOR9 and CO—Z in which Z is NR10R11 and R9 is hydrogen, C1-C6-alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R12 radicals, and R10 is hydrogen, C1-C6-alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which itself may also be substituted by one or two R12 radicals, and R11 is hydrogen, C1-C6-alkyl, branched or unbranched, which may also be and substituted by a phenyl ring which may also carry an R9 radical, and R12 can be hydrogen, C1-C4-alkyl, branched or unbranched, —O—C1-C4-alkyl, OH, Cl, F, Br, J, CF3, NO2, NH2, CN, COOH, COO—C1-C4-alkyl, —NHCO—C1-C4-alkyl, —NHCO-phenyl, —NHSO2—C1-C4-alkyl, NHSO2-phenyl, —SO2—C1-C4-alkyl and —SO2-phenyl, R13 is hydrogen, C1-C6-alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R12 radicals, and R14 is hydrogen, C1-C6-alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R12 radicals, and n is a number 0, 1 or 2, and m,q are, independently of one another, a number 0, 1, 2, 3 or 4.

公开(公告)号：US20100298326A1

公开(公告)日：2010-11-25

申请号：US11990652

申请日：2007-12-28

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： A61K31/5377 ,  C07D401/02 ,  A61K31/455 ,  C07D413/14 ,  C07D401/14 ,  A61K31/465 ,  A61P25/16 ,  A61P13/12 ,  A61P27/12 ,  A61P35/00 ,  A61P31/18

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.

公开(公告)号：US07728012B2

公开(公告)日：2010-06-01

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： A61K31/44 ,  C07D221/18 ,  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.

公开(公告)号：US20080234330A1

公开(公告)日：2008-09-25

申请号：US12072065

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.

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：US07799809B2

公开(公告)日：2010-09-21

申请号：US12072065

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： A61K31/44 ,  C07D221/18 ,  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：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：US08877194B2

公开(公告)日：2014-11-04

申请号：US13314878

申请日：2011-12-08

申请人： Chung-ming Hsieh ,  Carrie L. Goodreau ,  Sahana Bose ,  Achim Moeller ,  Tariq Ghayur

发明人： Chung-ming Hsieh ,  Carrie L. Goodreau ,  Sahana Bose ,  Achim Moeller ,  Tariq Ghayur

IPC分类号： A61K39/395 ,  C07K16/24

CPC分类号： C07K16/241 ,  A61K39/3955 ,  A61K45/06 ,  A61K47/48546 ,  A61K47/6845 ,  A61K49/0058 ,  A61K51/1021 ,  A61K2039/505 ,  A61K2039/54 ,  A61K2039/545 ,  C07K2317/14 ,  C07K2317/20 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2317/624 ,  C07K2317/626 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/30 ,  G01N33/6863

摘要： TNF-α binding proteins, including chimeric, CDR-grafted, and humanized antibodies that bind TNF-α are provided. Binding proteins have high affinity for TNF-α and neutralize TNF-α activity. A binding protein can be a full-length antibody or a TNF-α-binding portion thereof. Methods of making and methods of using the binding proteins are also described. The TNF-α binding proteins are useful for detecting TNF-α and for inhibiting TNF-α activity, including in a human subject suffering from a disease or disorder in which TNF-α activity is detrimental.

摘要翻译： 提供TNF-α结合蛋白，包括结合TNF-α的嵌合，CDR移植和人源化抗体。 结合蛋白对TNF-α具有高亲和力，并中和TNF-α活性。 结合蛋白可以是全长抗体或其TNF-α结合部分。 还描述了制备方法和使用结合蛋白的方法。 TNF-α结合蛋白可用于检测TNF-α和抑制TNF-α活性，包括在患有TNF-α活性有害的疾病或病症的人类受试者中。

公开(公告)号：US20130316126A1

公开(公告)日：2013-11-28

申请号：US13886447

申请日：2013-05-03

申请人： Achim Moeller ,  Thomas Eckstein

发明人： Achim Moeller ,  Thomas Eckstein

IPC分类号： E04C2/36 ,  B32B38/00

CPC分类号： E04C2/36 ,  B27D1/06 ,  B32B38/0004 ,  B32B38/0012 ,  Y10T156/10 ,  Y10T156/1043 ,  Y10T156/1059 ,  Y10T428/24066 ,  Y10T428/24074 ,  Y10T428/24091

摘要： A core layer, a multi-layered composite, and methods of producing the same are provided. The core layer includes a first layer having first stick-like elements and a second layer having second stick-like elements. In each layer the stick-like elements are spaced apart and separated from each other by a cavity. A first stick-like element in the first layer and a second stick-like element in the second layer include an angle with each other which is different from zero, and the first layer and the second layer are fixedly interconnected.

摘要翻译： 提供了核心层，多层复合材料及其制造方法。 芯层包括具有第一棒状元件的第一层和具有第二棒状元件的第二层。 在每个层中，棒状元件间隔开并且通过空腔彼此分离。 第一层中的第一棒状元件和第二层中的第二棒状元件包括彼此不同于零的角度，并且第一层和第二层被固定地互连。

公开(公告)号：US20130316125A1

公开(公告)日：2013-11-28

申请号：US13886444

申请日：2013-05-03

申请人： Achim Moeller ,  Thomas Eckstein ,  Johannes Graesser

发明人： Achim Moeller ,  Thomas Eckstein ,  Johannes Graesser

IPC分类号： E04C2/32

CPC分类号： E04C2/322 ,  E04C2/12 ,  E04C2/3405 ,  E04C2002/345 ,  E04C2002/3472 ,  Y10T156/10 ,  Y10T428/24066 ,  Y10T428/24719

摘要： A core layer, a multilayer composite, and methods of making and using the same are provided. The core layer includes wooden zigzag-shaped elements and is suitable for producing a multilayer composite, or for use in a multilayer composite. The multilayer composite includes at least one cover layer and a core layer, and the cover layer is arranged such that it at least partially covers the core layer and is fixedly connected to the core layer.

摘要翻译： 提供核心层，多层复合材料及其制造和使用方法。 芯层包括木状锯齿形元件，适用于生产多层复合材料，或用于多层复合材料。 多层复合材料包括至少一个覆盖层和芯层，并且覆盖层被布置成使得其至少部分地覆盖芯层并且固定地连接到芯层。