公开(公告)号：US07521457B2

公开(公告)日：2009-04-21

申请号：US11206703

申请日：2005-08-17

申请人： Heinz Stadtmueller ,  Harald Engelhardt ,  Martin Steegmaier ,  Anke Baum ,  Ulrich Guertler ,  Andreas Schoop ,  Jens Juergen Quant ,  Flavio Solca ,  Rudolf Hauptmann ,  Ulrich Reiser ,  Stephan Karl Zahn ,  Lars Herfurth

发明人： Heinz Stadtmueller ,  Harald Engelhardt ,  Martin Steegmaier ,  Anke Baum ,  Ulrich Guertler ,  Andreas Schoop ,  Jens Juergen Quant ,  Flavio Solca ,  Rudolf Hauptmann ,  Ulrich Reiser ,  Stephan Karl Zahn ,  Lars Herfurth

IPC分类号： C07D239/42 ,  C07D239/46 ,  A61K31/505 ,  A61K31/506 ,  A61P35/00

CPC分类号： C07D239/42 ,  C07D239/48 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D453/02 ,  C07D471/04 ,  C07D487/04 ,  C07D487/08 ,  C07D491/08 ,  C07D491/10

摘要： The present invention encompasses compounds of general formula (1), wherein A, W, X, Y, Z, Ra, Rb, Rc, R1 and R3 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a pharmaceutical composition having the above-mentioned properties.

摘要翻译： 本发明包括通式（1）的化合物，其中A，W，X，Y，Z，Ra，Rb，Rc，R 1和R 3如权利要求1中所定义，其适用于治疗以过量 或异常细胞增殖，以及其用于制备具有上述性质的药物组合物的用途。

公开(公告)号：US20060148800A1

公开(公告)日：2006-07-06

申请号：US11206703

申请日：2005-08-17

申请人： Heinz Stadtmueller ,  Harald Engelhardt ,  Martin Steegmaier ,  Anke Baum ,  Ulrich Guertler ,  Andreas Schoop ,  Jen Quant ,  Flavio Solca ,  Rudolf Hauptmann ,  Ulrich Reiser ,  Stephan Zahn ,  Lars Herfurth

发明人： Heinz Stadtmueller ,  Harald Engelhardt ,  Martin Steegmaier ,  Anke Baum ,  Ulrich Guertler ,  Andreas Schoop ,  Jen Quant ,  Flavio Solca ,  Rudolf Hauptmann ,  Ulrich Reiser ,  Stephan Zahn ,  Lars Herfurth

IPC分类号： A61K31/53

CPC分类号： C07D239/42 ,  C07D239/48 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D453/02 ,  C07D471/04 ,  C07D487/04 ,  C07D487/08 ,  C07D491/08 ,  C07D491/10

摘要： The present invention encompasses compounds of general formula (1), wherein A, W, X, Y, Z, Ra, Rb, Rc, R1 and R3 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a pharmaceutical composition having the above-mentioned properties.

公开(公告)号：US20070207999A1

公开(公告)日：2007-09-06

申请号：US11675936

申请日：2007-02-16

申请人： Heinz Stadtmueller ,  Anke Baum ,  Guido Boehmelt ,  Harald Engelhardt ,  Jens Quant ,  Flavio Solca ,  Martin Steegmaier ,  Stephan Zahn

发明人： Heinz Stadtmueller ,  Anke Baum ,  Guido Boehmelt ,  Harald Engelhardt ,  Jens Quant ,  Flavio Solca ,  Martin Steegmaier ,  Stephan Zahn

IPC分类号： A61K31/55 ,  A61K31/553 ,  C07D403/02 ,  C07D413/02

CPC分类号： C07D498/04 ,  C07D403/12 ,  C07D413/12 ,  C07D487/04

摘要： The present invention encompasses compounds of general formula (1) wherein R1 to R6, X and Y are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or anomalous cell proliferation, as well as the use thereof for preparing a pharmaceutical composition with the above-mentioned properties.

摘要翻译： 本发明包括其中R 1至R 6的通式（1）的化合物，X和Y如权利要求1中所定义，其适用于治疗疾病 其特征在于过度或异常的细胞增殖，以及其用于制备具有上述性质的药物组合物的用途。

公开(公告)号：US08586608B2

公开(公告)日：2013-11-19

申请号：US12563340

申请日：2009-09-21

申请人： Frank Himmelsbach ,  Elke Langkopf ,  Stefan Blech ,  Birgit Jung ,  Anke Baum ,  Flavio Solca

发明人： Frank Himmelsbach ,  Elke Langkopf ,  Stefan Blech ,  Birgit Jung ,  Anke Baum ,  Flavio Solca

IPC分类号： A61K31/47 ,  A01N43/42

CPC分类号： C07D405/12 ,  C07D239/94

摘要： A compound of general formula I wherein: Ra is a benzyl, 1-phenylethyl, or 3-chloro-4-fluorophenyl group; Rb is a dimethylamino, N-methyl-N-ethylamino, diethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetra-hydrofuran-3-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetra-hydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and Rc is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group, or a tautomer, stereoisomer, or salt thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.

摘要翻译： 通式I的化合物，其中：R a是苄基，1-苯乙基或3-氯-4-氟苯基; Rb是二甲基氨基，N-甲基-N-乙基氨基，二乙基氨基，N-甲基-N-异丙基氨基，N-甲基-N-环丙基氨基，N-甲基-N-（2-甲氧基乙基）氨基，N-乙基-N- （2-甲氧基乙基）氨基，双（2-甲氧基乙基）氨基，吗啉代，N-甲基-N-（四氢呋喃-3-基）氨基，N-甲基-N-（四氢呋喃-2-基甲基）氨基，N - 甲基-N-（四氢呋喃-3-基甲基）氨基，N-甲基-N-（四氢吡喃-4-基）氨基或N-甲基-N-（四氢吡喃-4-基甲基）氨基; Rc为环丙基甲氧基，环丁氧基，环戊氧基，四氢呋喃-3-基氧基，四氢呋喃-2-基甲氧基，四氢呋喃-3-基甲氧基，四氢吡喃-4-基氧基或四氢吡喃-4-基甲氧基，或互变异构体，立体异构体或盐 特别是其具有有价值的药理学特性的无机或有机酸或碱的生理上可接受的盐，特别是对由酪氨酸激酶介导的信号转导的抑制作用，它们在治疗疾病尤其是肿瘤疾病和肺疾病中的用途 和气道及其制备。

公开(公告)号：US20060100223A1

公开(公告)日：2006-05-11

申请号：US11313304

申请日：2005-12-21

申请人： Frank Himmelsbach ,  Elke Langkopf ,  Stefan Blech ,  Birgit Jung ,  Anke Baum ,  Flavio Solca

发明人： Frank Himmelsbach ,  Elke Langkopf ,  Stefan Blech ,  Birgit Jung ,  Anke Baum ,  Flavio Solca

IPC分类号： A61K31/517 ,  C07D405/02 ,  C07D239/84

CPC分类号： C07D405/12 ,  C07D239/94

摘要： A compound of general formula I wherein: Ra is a benzyl, 1-phenylethyl, or 3-chloro-4-fluorophenyl group; Rb is a dimethylamino, N-methyl-N-ethylamino, diethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetrahydrofuran-3-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetrahydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and Rc is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group, or a tautomer, stereoisomer, or salt thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.

公开(公告)号：US07220750B2

公开(公告)日：2007-05-22

申请号：US10016280

申请日：2001-12-10

申请人： Frank Himmelsbach ,  Elke Langkopf ,  Thomas Metz ,  Flavio Solca ,  Birgit Jung ,  Anke Baum

发明人： Frank Himmelsbach ,  Elke Langkopf ,  Thomas Metz ,  Flavio Solca ,  Birgit Jung ,  Anke Baum

IPC分类号： A61K31/517 ,  A61K31/47 ,  C07D239/72 ,  C07D215/38

CPC分类号： C07D405/12 ,  C07D215/42 ,  C07D215/54 ,  C07D239/94 ,  C07D401/12

摘要： The present invention relates to bicyclic heterocycles of general formula wherein Ra to Rc, A to E and X are defined as in claim 1, the tautomers, stereoisomers and salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.

摘要翻译： 本发明涉及通式的双环杂环，其中R a至R c，A至E和X如权利要求1所定义，互变异构体，立体异构体及其盐 特别是其具有有价值的药理学特性的无机或有机酸或碱的生理上可接受的盐，特别是对由酪氨酸激酶介导的信号转导的抑制作用，它们在治疗疾病尤其是肿瘤疾病和肺疾病中的用途以及 气道及其制备。

公开(公告)号：US20050043233A1

公开(公告)日：2005-02-24

申请号：US10830147

申请日：2004-04-22

申请人： Martin Stefanic ,  Frank Hilberg ,  Gerd Munzert ,  Flavio Solca ,  Anke Baum ,  Jacobus van Meel

发明人： Martin Stefanic ,  Frank Hilberg ,  Gerd Munzert ,  Flavio Solca ,  Anke Baum ,  Jacobus van Meel

IPC分类号： A61K31/496 ,  A61K31/517 ,  A61K31/56 ,  A61K45/06 ,  A61P35/00 ,  A61K38/17

CPC分类号： A61K31/496 ,  A61K31/404 ,  A61K31/517 ,  A61K31/553 ,  A61K31/56 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention relates to a pharmaceutical combination for the treatment of diseases which involves cell proliferation, migration or apoptosis of myeloma cells, or angiogenesis. The invention also relates to a method for the treatment of said diseases, comprising co-administration of effective amounts of specific active compounds and/or co-treatment with radiation therapy, in a ratio which provides an additive and synergistic effect, and to the combined use of these specific compounds and/or radiotherapy for the manufacture of corresponding pharmaceutical combination preparations.

摘要翻译： 本发明涉及用于治疗涉及骨髓瘤细胞的细胞增殖，迁移或凋亡或血管发生的疾病的药物组合。 本发明还涉及一种治疗所述疾病的方法，包括以提供添加剂和协同效应的比例共同给予有效量的特定活性化合物和/或与放射治疗共同给药，以及组合 使用这些特定化合物和/或放射治疗来制造相应的药物组合制剂。

公开(公告)号：US08722694B2

公开(公告)日：2014-05-13

申请号：US13603476

申请日：2012-09-05

申请人： Frank Himmelsbach ,  Elke Langkopf ,  Thomas Metz ,  Flavio Solca ,  Birgit Jung ,  Anke Baum

发明人： Frank Himmelsbach ,  Elke Langkopf ,  Thomas Metz ,  Flavio Solca ,  Birgit Jung ,  Anke Baum

IPC分类号： A61K31/517

CPC分类号： C07D405/12 ,  C07D215/42 ,  C07D215/54 ,  C07D239/94 ,  C07D401/12

摘要： The present invention relates to bicyclic heterocycles of general formula wherein Ra to Rc, A to E and X are defined as in claim 1, the tautomers, stereoisomers and salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.

摘要翻译： 本发明涉及通式的双环杂环，其中R a至R c，A至E和X如权利要求1中所定义，互变异构体，立体异构体和盐，特别是其与无机或有机酸或碱的生理上可接受的盐，其具有 特别是对由酪氨酸激酶介导的信号转导的抑制作用，它们在治疗疾病尤其是肿瘤疾病和肺和气道疾病中的应用及其制备。

公开(公告)号：USRE43431E1

公开(公告)日：2012-05-29

申请号：US12542929

申请日：2009-08-18

申请人： Frank Himmelsbach ,  Elke Langkopf ,  Stefan Blech ,  Birgit Jung ,  Anke Baum ,  Flavio Solca

发明人： Frank Himmelsbach ,  Elke Langkopf ,  Stefan Blech ,  Birgit Jung ,  Anke Baum ,  Flavio Solca

IPC分类号： A61K31/517 ,  C07D239/94 ,  C07D413/02

CPC分类号： C07D405/12 ,  C07D239/94

摘要： A compound of general formula I wherein: Ra is a benzyl, 1-phenylethyl, or 3-chloro-4-fluorophenyl group; Rb is a dimethylamino, N-methyl-N-ethylamino, diethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetrahydrofuran-3-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetrahydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and Rc is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group, or a tautomer, stereoisomer, or salt thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.

摘要翻译： 通式I的化合物，其中：R a是苄基，1-苯乙基或3-氯-4-氟苯基; Rb是二甲基氨基，N-甲基-N-乙基氨基，二乙基氨基，N-甲基-N-异丙基氨基，N-甲基-N-环丙基氨基，N-甲基-N-（2-甲氧基乙基）氨基，N-乙基-N- （2-甲氧基乙基）氨基，双（2-甲氧基乙基）氨基，吗啉代，N-甲基-N-（四氢呋喃-3-基）氨基，N-甲基-N-（四氢呋喃-2-基甲基）氨基，N-甲基 -N-（四氢呋喃-3-基甲基）氨基，N-甲基-N-（四氢吡喃-4-基）氨基或N-甲基-N-（四氢吡喃-4-基甲基）氨基; Rc为环丙基甲氧基，环丁氧基，环戊氧基，四氢呋喃-3-基氧基，四氢呋喃-2-基甲氧基，四氢呋喃-3-基甲氧基，四氢吡喃-4-基氧基或四氢吡喃-4-基甲氧基，或互变异构体，立体异构体或盐 特别是其具有有价值的药理学特性的无机或有机酸或碱的生理上可接受的盐，特别是对由酪氨酸激酶介导的信号转导的抑制作用，它们在治疗疾病尤其是肿瘤疾病和肺疾病中的用途 和气道及其制备。

公开(公告)号：US07019012B2

公开(公告)日：2006-03-28

申请号：US10023099

申请日：2001-12-17

申请人： Frank Himmelsbach ,  Elke Langkopf ,  Stefan Blech ,  Birgit Jung ,  Anke Baum ,  Flavio Solca

发明人： Frank Himmelsbach ,  Elke Langkopf ,  Stefan Blech ,  Birgit Jung ,  Anke Baum ,  Flavio Solca

IPC分类号： A61K31/5377 ,  A61K31/517 ,  C07D239/72 ,  C07D413/02

CPC分类号： C07D405/12 ,  C07D239/94

摘要： A compound of general formula I wherein: Ra is a benzyl, 1-phenylethyl, or 3-chloro-4-fluorophenyl group; Rb is a dimethylamino, N-methyl-N-ethylamino, diethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetrahydrofuran-3-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetrahydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and Rc is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group, or a tautomer, stereoisomer, or salt thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.

摘要翻译： 通式I的化合物，其中：R a a是苄基，1-苯乙基或3-氯-4-氟苯基; R b是二甲基氨基，N-甲基-N-乙基氨基，二乙基氨基，N-甲基-N-异丙基氨基，N-甲基-N-环丙基氨基，N-甲基-N-（2-甲氧基乙基） 氨基，N-乙基-N-（2-甲氧基乙基）氨基，双（2-甲氧基乙基）氨基，吗啉代，N-甲基-N-（四氢呋喃-3-基）氨基，N-甲基-N-（四氢呋喃-2 - 甲基）氨基，N-甲基-N-（四氢呋喃-3-基甲基）氨基，N-甲基-N-（四氢吡喃-4-基）氨基或N-甲基-N-（四氢吡喃-4-基甲基）氨基 组; 环烷基甲氧基，环丁氧基，四氢呋喃-3-基氧基，四氢呋喃-2-基甲氧基，四氢呋喃-3-基甲氧基，四氢吡喃-4-基氧基或四氢吡喃-4-基甲氧基， 或其互变异构体，立体异构体或其盐，特别是其具有有价值的药理学性质的无机或有机酸或碱的生理上可接受的盐，特别是对由酪氨酸激酶介导的信号转导的抑制作用，它们在治疗疾病中的用途， 特别是肺和气道的肿瘤疾病和疾病及其制备。