公开(公告)号：US08716282B2

公开(公告)日：2014-05-06

申请号：US13096545

申请日：2011-04-28

申请人： Joaquin Pastor-Fernández ,  José Manuel Bartolomé-Nebreda ,  Gregor James Macdonald ,  Susana Conde-Ceide ,  Óscar Delgado-González ,  Greta Constantia Peter Vanhoof ,  Michiel Luc Maria Van Gool ,  María Luz Martín-Martín ,  Sergio-Alvar Alonso-de Diego ,  Kelly Ann Swinney ,  Carina Leys ,  Johan Erwin Edmond Weerts ,  Stijn Wuyts

发明人： Joaquin Pastor-Fernández ,  José Manuel Bartolomé-Nebreda ,  Gregor James Macdonald ,  Susana Conde-Ceide ,  Óscar Delgado-González ,  Greta Constantia Peter Vanhoof ,  Michiel Luc Maria Van Gool ,  María Luz Martín-Martín ,  Sergio-Alvar Alonso-de Diego ,  Kelly Ann Swinney ,  Carina Leys ,  Johan Erwin Edmond Weerts ,  Stijn Wuyts

IPC分类号： A61K31/5025 ,  A61K31/5377 ,  C07D413/14 ,  C07D403/14 ,  C07D487/04

CPC分类号： C07D487/04

摘要： The present invention relates to novel imidazo[1,2-b]pyridazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which are useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.

摘要翻译： 本发明涉及作为磷酸二酯酶10酶（PDE10）的抑制剂的新的咪唑并[1,2-b]哒嗪衍生物，它们可用于治疗或预防涉及PDE10酶的神经，精神和代谢紊乱 。 本发明还涉及包含这些化合物的药物组合物，以制备这些化合物和组合物以使用这些化合物或药物组合物来预防或治疗神经，精神和代谢疾病和疾病。

公开(公告)号：US20110269752A1

公开(公告)日：2011-11-03

申请号：US13096545

申请日：2011-04-28

申请人： Joaquin Pastor-Fernández ,  José Manuel Bartolomé-Nebreda ,  Gregor James Macdonald ,  Susana Conde-Ceide ,  Óscar Delgado-González ,  Greta Constantia Peter Vanhoof ,  Michiel Luc Maria Van Gool ,  María Luz Martin-Martín ,  Sergio-Alvar Alonso-de Diego ,  Kelly Ann Swinney ,  Carina Leys ,  Johan Erwin Edmond Weerts ,  Stijn Wuyts

发明人： Joaquin Pastor-Fernández ,  José Manuel Bartolomé-Nebreda ,  Gregor James Macdonald ,  Susana Conde-Ceide ,  Óscar Delgado-González ,  Greta Constantia Peter Vanhoof ,  Michiel Luc Maria Van Gool ,  María Luz Martin-Martín ,  Sergio-Alvar Alonso-de Diego ,  Kelly Ann Swinney ,  Carina Leys ,  Johan Erwin Edmond Weerts ,  Stijn Wuyts

IPC分类号： A61K31/5377 ,  C07D471/04 ,  A61K31/5025 ,  A61P25/18 ,  A61P3/00 ,  A61P25/14 ,  A61P25/28 ,  A61P25/30 ,  A61P25/00 ,  C07D413/14 ,  A61P25/22

CPC分类号： C07D487/04

摘要： The present invention relates to novel imidazo[1,2-b]pyridazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which are useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.

摘要翻译： 本发明涉及作为磷酸二酯酶10酶（PDE10）的抑制剂的新的咪唑并[1,2-b]哒嗪衍生物，它们可用于治疗或预防涉及PDE10酶的神经，精神和代谢紊乱 。 本发明还涉及包含这些化合物的药物组合物，以制备这些化合物和组合物以使用这些化合物或药物组合物来预防或治疗神经，精神和代谢疾病和疾病。

公开(公告)号：US20100130523A1

公开(公告)日：2010-05-27

申请号：US12598743

申请日：2008-05-13

申请人： Julius W.J. Dickens ,  Ioannes Nicolaos Houpis ,  Yolande Lydia Lang ,  Carina Leys ,  Sigrid Carl Maria Stokbroekx ,  Johan Erwin Edmond Weerts

发明人： Julius W.J. Dickens ,  Ioannes Nicolaos Houpis ,  Yolande Lydia Lang ,  Carina Leys ,  Sigrid Carl Maria Stokbroekx ,  Johan Erwin Edmond Weerts

IPC分类号： A61K31/506 ,  C07D211/28 ,  C07D401/14 ,  A61P35/00 ,  A61P35/02

CPC分类号： C07D211/26 ,  C07D401/14

摘要： This invention provides novel crystalline forms of mono-HCl salts and a mono-HCl salt hydrate of JNJ-26481585, an inhibitor of histone deacetylases. The invention also relates to processes for production of these forms, to intermediates used in these processes, to pharmaceutical compositions comprising these forms, and to the use of these forms in medical treatment for instance as a medicine to inhibit proliferative conditions, such as cancer and leukemia.

摘要翻译： 本发明提供了单盐酸盐和组蛋白脱乙酰酶抑制剂JNJ-26481585的单盐酸盐水合物的新型结晶形式。 本发明还涉及这些形式的制备方法，这些方法中使用的中间体，包含这些形式的药物组合物，以及这些形式在医学治疗中的用途，例如作为抑制增殖性疾病的药物，例如癌症和 白血病。

公开(公告)号：US20120289527A1

公开(公告)日：2012-11-15

申请号：US13483678

申请日：2012-05-30

申请人： Julius W.J. Dickens ,  Ioannes Nicolaos Houpis ,  Yolande Lydia Lang ,  Carina Leys ,  Sigrid Carl Maria Stokbroekx ,  Johan Erwin Edmond Weerts

发明人： Julius W.J. Dickens ,  Ioannes Nicolaos Houpis ,  Yolande Lydia Lang ,  Carina Leys ,  Sigrid Carl Maria Stokbroekx ,  Johan Erwin Edmond Weerts

IPC分类号： C07D401/14 ,  A61K31/506 ,  A61P35/00 ,  C07D211/28

CPC分类号： C07D211/26 ,  C07D401/14

摘要： This invention provides novel crystalline forms of mono-HCl salts and a mono-HCl salt hydrate of JNJ-26481585, an inhibitor of histone deacetylases. The invention also relates to processes for production of these forms, to intermediates used in these processes, to pharmaceutical compositions comprising these forms, and to the use of these forms in medical treatment for instance as a medicine to inhibit proliferative conditions, such as cancer and leukemia.

摘要翻译： 本发明提供了单盐酸盐和组蛋白脱乙酰酶抑制剂JNJ-26481585的单盐酸盐水合物的新型结晶形式。 本发明还涉及这些形式的制备方法，这些方法中使用的中间体，包含这些形式的药物组合物，以及这些形式在医学治疗中的用途，例如作为抑制增殖性疾病的药物，例如癌症和 白血病。

公开(公告)号：US08629144B2

公开(公告)日：2014-01-14

申请号：US12665192

申请日：2008-06-19

申请人： Tom Cornelis Hortense Govaerts ,  Johan Erwin Edmond Weerts ,  Carina Leys ,  Julius Walter Jozef Dickens ,  Sigrid Carl Maria Stokbroekx

发明人： Tom Cornelis Hortense Govaerts ,  Johan Erwin Edmond Weerts ,  Carina Leys ,  Julius Walter Jozef Dickens ,  Sigrid Carl Maria Stokbroekx

IPC分类号： A61K31/50

CPC分类号： C07D487/04

摘要： The invention relates to novel polymorphic and hydrate forms and salts of 6-{difluoro[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}quinoline, to methods for their preparation, to pharmaceutical compositions comprising at least one of said polymorphic or hydrate forms or salts, and to the therapeutic and/or prophylactic use of such compositions. The invention also provides new manners for preparing said compound.

摘要翻译： 本发明涉及6- {二氟[6-（1-甲基-1H-吡唑-4-基）[1,2,4]三唑并[4,3-b]哒嗪-3的新型多晶型和水合物形式和盐 - 基]甲基}喹啉，其制备方法，包含至少一种所述多晶型或水合物形式或盐的药物组合物，以及该组合物的治疗和/或预防用途。 本发明还提供了制备所述化合物的新方式。

公开(公告)号：US08759519B2

公开(公告)日：2014-06-24

申请号：US13483678

申请日：2012-05-30

申请人： Julius W. J. Dickens ,  Ioannes Nicolaos Houpis ,  Yolande Lydia Lang ,  Carina Leys ,  Sigrid Carl Maria Stokbroekx ,  Johan Erwin Edmond Weerts

发明人： Julius W. J. Dickens ,  Ioannes Nicolaos Houpis ,  Yolande Lydia Lang ,  Carina Leys ,  Sigrid Carl Maria Stokbroekx ,  Johan Erwin Edmond Weerts

IPC分类号： C07D405/14 ,  C07D211/26

CPC分类号： C07D211/26 ,  C07D401/14

摘要： This invention provides novel crystalline forms of mono-HCl salts and a mono-HCl salt hydrate of JNJ-26481585, an inhibitor of histone deacetylases. The invention also relates to processes for production of these forms, to intermediates used in these processes, to pharmaceutical compositions comprising these forms, and to the use of these forms in medical treatment for instance as a medicine to inhibit proliferative conditions, such as cancer and leukemia.

摘要翻译： 本发明提供了单盐酸盐和组蛋白脱乙酰酶抑制剂JNJ-26481585的单盐酸盐水合物的新型结晶形式。 本发明还涉及这些形式的制备方法，这些方法中使用的中间体，包含这些形式的药物组合物，以及这些形式在医学治疗中的用途，例如作为抑制增殖性疾病的药物，例如癌症和 白血病。

公开(公告)号：US20100197912A1

公开(公告)日：2010-08-05

申请号：US12665192

申请日：2008-06-19

申请人： Tom Cornelis Hortense Govaerts ,  Johan Erwin Edmond Weerts ,  Carina Leys ,  Julius Walter Jozef Dickens ,  Sigrid Carl Maria Stokbroekx

发明人： Tom Cornelis Hortense Govaerts ,  Johan Erwin Edmond Weerts ,  Carina Leys ,  Julius Walter Jozef Dickens ,  Sigrid Carl Maria Stokbroekx

IPC分类号： C07D487/04

CPC分类号： C07D487/04

摘要： The invention relates to novel polymorphic and hydrate forms and salts of 6-{difluoro[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}quinoline, to methods for their preparation, to pharmaceutical compositions comprising at least one of said polymorphic or hydrate forms or salts, and to the therapeutic and/or prophylactic use of such compositions. The invention also provides new manners for preparing said compound.

摘要翻译： 本发明涉及6- {二氟[6-（1-甲基-1H-吡唑-4-基）[1,2,4]三唑并[4,3-b]哒嗪-3的新型多晶型和水合物形式和盐 - 基]甲基}喹啉，其制备方法，包含至少一种所述多晶型或水合物形式或盐的药物组合物，以及该组合物的治疗和/或预防用途。 本发明还提供了制备所述化合物的新方式。

公开(公告)号：US20050085533A1

公开(公告)日：2005-04-21

申请号：US10491799

申请日：2002-11-08

申请人： Bart Petrus Anna Maria Jozef Medaer ,  Sigrid Carl Maria Stokbroekx ,  Yves Ruysschaert ,  Joannes Josephus Maria Willems ,  Johan Erwin Edmond Weerts

发明人： Bart Petrus Anna Maria Jozef Medaer ,  Sigrid Carl Maria Stokbroekx ,  Yves Ruysschaert ,  Joannes Josephus Maria Willems ,  Johan Erwin Edmond Weerts

IPC分类号： A61K31/343 ,  A61P9/00 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  C07D307/93

CPC分类号： C07D307/93

摘要： The object of the present invention is a novel mandelate salt of a substituted tetracyclic tetrahydrofuran derivative according to Formula (I) the N-oxide forms and the stereochemically isomeric forms thereof, wherein R1 and R2 each independently are hydrogen or C1-6alkyl and R3 and R4 each independently are hydrogen or halogen. In the foregoing definitions C1-6alkyl defines straight and branched saturated hydrocarbon radicals having from 1 to 6 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylpropyl, 1,1-dimethylethyl, pentyl or hexyl. The novel mandelate salt is not light-sensitive and is far more stable than the prior art salts at room temperature, enhanced temperature and at relative high humidities and in aqueous media. Also disclosed are pharmaceutical compositions comprising mandelate salts according to the invention, mandelate salts according to the invention for use as a medicine, a process for preparing the mandelate salts according to the invention and the use of the mandelate salts and pharmaceutical compositions comprising mandelate salts according to the invention for the treatment or the prevention of CNS disorders, cardiovascular disorders and gastrointestinal disorders.

摘要翻译： 本发明的目的是根据式（I）的N-氧化物形式及其立体化学异构形式的取代四环四氢呋喃衍生物的新型扁桃酸盐，其中R 1和R 2， 2个独立地为氢或C 1-6烷基，R 3和R 4各自独立地为氢或卤素。 在上述定义中，C 1-6烷基定义了具有1至6个碳原子的直链和支链饱和烃基，例如甲基，乙基，丙基，丁基，1-甲基丙基， 1-二甲基乙基，戊基或己基。 新颖的扁桃酸盐盐不敏感，并且在室温，升高的温度和相对高的湿度和水性介质中比现有技术的盐更稳定。 还公开了包含根据本发明的扁桃酸盐的药物组合物，根据本发明的用作药物的扁桃酸盐，根据本发明的扁桃酸盐的制备方法以及包含扁桃酸盐的扁桃酸盐和药物组合物的用途，所述扁桃酸盐包括扁桃酸盐 涉及用于治疗或预防CNS疾病，心血管疾病和胃肠道疾病的本发明。

公开(公告)号：US20130072457A1

公开(公告)日：2013-03-21

申请号：US13643741

申请日：2011-04-28

申请人： Gordon Saxty ,  Christopher William Murray ,  Valerio Berdini ,  Gilbert Ebai Besong ,  Christopher Charles Frederick Hamlett ,  Christopher Norbert Johnson ,  Steven John Woodhead ,  Michael Reader ,  David Charles Rees ,  Laurence Anne Mevellec ,  Patrick René Angibaud ,  Eddy Jean Edgard Freyne ,  Tom Cornelis Hortense Govaerts ,  Johan Erwin Edmond Weerts ,  Timothy Pietro Suren Perera ,  Ronaldus Arnodus Hendrika Joseph Gilissen ,  Berthold Wroblowski ,  Jean Fernand Armand Lacrampe ,  Alexandra Papanikos ,  Oliver Alexis Georges Querolle ,  Elisabeth Thérèse Jeanne Pasquier ,  Isabelle Noëlle Constance Pilatte ,  Pascal Ghislain André Bonnet ,  Werner Constant Johan Embrechts ,  Rhalid Akkari ,  Lieven Meerpoel

发明人： Gordon Saxty ,  Christopher William Murray ,  Valerio Berdini ,  Gilbert Ebai Besong ,  Christopher Charles Frederick Hamlett ,  Christopher Norbert Johnson ,  Steven John Woodhead ,  Michael Reader ,  David Charles Rees ,  Laurence Anne Mevellec ,  Patrick René Angibaud ,  Eddy Jean Edgard Freyne ,  Tom Cornelis Hortense Govaerts ,  Johan Erwin Edmond Weerts ,  Timothy Pietro Suren Perera ,  Ronaldus Arnodus Hendrika Joseph Gilissen ,  Berthold Wroblowski ,  Jean Fernand Armand Lacrampe ,  Alexandra Papanikos ,  Oliver Alexis Georges Querolle ,  Elisabeth Thérèse Jeanne Pasquier ,  Isabelle Noëlle Constance Pilatte ,  Pascal Ghislain André Bonnet ,  Werner Constant Johan Embrechts ,  Rhalid Akkari ,  Lieven Meerpoel

IPC分类号： C07D403/04 ,  C07D405/14 ,  C07D491/113 ,  C07D401/14 ,  C07D413/14 ,  A61K31/5377 ,  C07D487/08 ,  C07F9/6558 ,  A61K31/675 ,  C07D491/107 ,  C07D471/04 ,  C07D403/14 ,  A61K31/506 ,  A61P35/00 ,  A61K31/498

CPC分类号： C07D403/04 ,  A61K31/498 ,  A61K31/5377 ,  A61K45/06 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D487/08 ,  C07D491/113 ,  C07F9/6524

摘要： The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

摘要翻译： 本发明涉及新的喹喔啉衍生物化合物，包含所述化合物的药物组合物，用于制备所述化合物的方法和所述化合物在治疗疾病中的用途。 癌症。

公开(公告)号：US07317115B2

公开(公告)日：2008-01-08

申请号：US10491799

申请日：2002-11-08

申请人： Bart Petrus Anna Maria Jozef Medaer ,  Sigrid Carl Maria Stokbroekx ,  Yves Georges Ruysschaert ,  Joannes Josephus Maria Willems ,  Johan Erwin Edmond Weerts

发明人： Bart Petrus Anna Maria Jozef Medaer ,  Sigrid Carl Maria Stokbroekx ,  Yves Georges Ruysschaert ,  Joannes Josephus Maria Willems ,  Johan Erwin Edmond Weerts

IPC分类号： C07D307/77

CPC分类号： C07D307/93

摘要： The object of the present invention is a novel mandelate salt of a substituted tetracyclic tetrahydrofuran derivative according to Formula (I) the N-oxide forms and the stereochemically isomeric forms thereof, wherein R1 and R2 each independently are hydrogen or C1-6alkyl and R3 and R4 each independently are hydrogen or halogen. In the foregoing definitions C1-6alkyl defines straight and branched saturated hydrocarbon radicals having from 1 to 6 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylpropyl, 1,1-dimethylethyl, pentyl or hexyl. The novel mandelate salt is not light-sensitive and is far more stable than the prior art salts at room temperature, enhanced temperature and at relative high humidities and in aqueous media. Also disclosed are pharmaceutical compositions comprising mandelate salts according to the invention, mandelate salts according to the invention for use as a medicine, a process for preparing the mandelate salts according to the invention and the use of the mandelate salts and pharmaceutical compositions comprising mandelate salts according to the invention for the treatment or the prevention of CNS disorders, cardiovascular disorders and gastrointestinal disorders.

摘要翻译： 本发明的目的是根据式（I）的N-氧化物形式及其立体化学异构形式的取代四环四氢呋喃衍生物的新型扁桃酸盐，其中R 1和R 2， 2个独立地为氢或C 1-6烷基，R 3和R 4各自独立地为氢或卤素。 在上述定义中，C 1-6烷基定义了具有1至6个碳原子的直链和支链饱和烃基，例如甲基，乙基，丙基，丁基，1-甲基丙基， 1-二甲基乙基，戊基或己基。 新颖的扁桃酸盐盐不敏感，并且在室温，升高的温度和相对高的湿度和水性介质中比现有技术的盐更稳定。 还公开了包含根据本发明的扁桃酸盐的药物组合物，根据本发明的用作药物的扁桃酸盐，根据本发明的扁桃酸盐的制备方法以及包含扁桃酸盐的扁桃酸盐和药物组合物的用途，所述扁桃酸盐包括扁桃酸盐 涉及用于治疗或预防CNS疾病，心血管疾病和胃肠道疾病的本发明。