公开(公告)号：US20090036471A1

公开(公告)日：2009-02-05

申请号：US12211361

申请日：2008-09-16

申请人： Eddy Jean Edgard ,  Christopher John Love ,  Ludwig Paul Cooymans ,  Nele Vandermaesen ,  Peter Jacobus Johannes Antonius Buijnsters ,  Marc Willems ,  Werner Constant Johan Embrechts

发明人： Eddy Jean Edgard ,  Christopher John Love ,  Ludwig Paul Cooymans ,  Nele Vandermaesen ,  Peter Jacobus Johannes Antonius Buijnsters ,  Marc Willems ,  Werner Constant Johan Embrechts

IPC分类号： A61K31/519 ,  A61P25/00 ,  A61P3/10 ,  A61P29/00 ,  A61P17/00

CPC分类号： C07D487/04

摘要： This invention concerns compounds of formula N-oxides, pharmaceutically acceptable addition salts, quaternary amines and stereochemically isomeric forms thereof, their use, pharmaceutical compositions comprising them, processes for their preparation, and methods of their use.

摘要翻译： 本发明涉及式N-氧化物的化合物，药学上可接受的加成盐，季胺及其立体化学异构形式，它们的用途，包含它们的药物组合物，其制备方法及其使用方法。

公开(公告)号：US08318929B2

公开(公告)日：2012-11-27

申请号：US12921499

申请日：2009-03-09

申请人： Peter Jacobus Johannes Antonius Buijnsters ,  Marc Gustaaf Celine Verdonck ,  Kristof Van Emelen ,  Pascal Ghislain André Bonnet

发明人： Peter Jacobus Johannes Antonius Buijnsters ,  Marc Gustaaf Celine Verdonck ,  Kristof Van Emelen ,  Pascal Ghislain André Bonnet

IPC分类号： C07D345/00

CPC分类号： C07D471/08 ,  C07D471/18 ,  C07D471/22 ,  C07D498/08 ,  C07D498/18

摘要： The present invention relates to compounds of Formula (Ia) or (Ib), the N-oxide forms, pharmaceutically acceptable addition salts, quaternary amines, stereoisomers, tautomers, racemics, metabolites, prodrugs, hydrates, or solvates thereof, wherein Y1, m, n, R1; X1; X2; R2; X3; X4; R3; and R4 have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to compounds that are kinase inhibitors useful for the treatment of disease states mediated by kinase, especially PLK4, in particular such compounds that are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.

摘要翻译： 本发明涉及式（Ia）或（Ib）的化合物，N-氧化物形式，药学上可接受的加成盐，季胺，立体异构体，互变异构体，外消旋学，代谢物，前药，水合物或溶剂化物，其中Y1， ，n，R1; X1; X2; R2; X3; X4; R3; 和R4具有权利要求中限定的含义。 本发明还涉及制备所述化合物的方法，含有它们的药物组合物及其在治疗中的用途。 本发明特别涉及可用于治疗由激酶，特别是PLK4介导的疾病状态的激酶抑制剂的化合物，特别是可用于治疗涉及异常细胞增殖的病理过程的化合物，例如肿瘤生长，类风湿 关节炎，再狭窄和动脉粥样硬化。

公开(公告)号：US20100190786A1

公开(公告)日：2010-07-29

申请号：US12663158

申请日：2008-06-20

申请人： Gaston Stanislas Marcella Diels ,  Marc Gustaaf Celine Verdonck ,  Peter Jacobus Johannes Antonius Buijnsters ,  Kristof Van Emelen

发明人： Gaston Stanislas Marcella Diels ,  Marc Gustaaf Celine Verdonck ,  Peter Jacobus Johannes Antonius Buijnsters ,  Kristof Van Emelen

IPC分类号： A61K31/5377 ,  A61K31/497 ,  A61K31/529 ,  C07D498/18 ,  A61P19/02 ,  A61P35/04

CPC分类号： C07D209/34 ,  C07D471/04 ,  C07D487/04

摘要： The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to certain indolin-2-ones and aza-indolin-2-ones which possess anti-tumour activity and are accordingly useful in methods of treatment of the human or animal body, in particular such compounds are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.

摘要翻译： 本发明涉及其化合物或药学上可接受的盐，其制备方法，含有它们的药物组合物及其在治疗中的用途。 本发明特别涉及具有抗肿瘤活性的某些二氢吲哚-2-酮和氮杂 - 二氢吲哚-2-酮，因此可用于人或动物体的治疗方法，特别是这些化合物可用于治疗 涉及异常细胞增殖的病理过程，例如肿瘤生长，类风湿性关节炎，再狭窄和动脉粥样硬化。

公开(公告)号：US08338422B2

公开(公告)日：2012-12-25

申请号：US12663158

申请日：2008-06-20

申请人： Gaston Stanislas Marcella Diels ,  Marc Gustaaf Celine Verdonck ,  Peter Jacobus Johannes Antonius Buijnsters ,  Kristof Van Emelen

发明人： Gaston Stanislas Marcella Diels ,  Marc Gustaaf Celine Verdonck ,  Peter Jacobus Johannes Antonius Buijnsters ,  Kristof Van Emelen

IPC分类号： C07D209/34 ,  C07D471/04 ,  C07D487/04 ,  A61K31/404 ,  A61K31/407 ,  A61P35/00

CPC分类号： C07D209/34 ,  C07D471/04 ,  C07D487/04

摘要： The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to certain indolin-2-ones and aza-indolin-2-ones which possess anti-tumor activity and are accordingly useful in methods of treatment of the human or animal body, in particular such compounds are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.

摘要翻译： 本发明涉及其化合物或药学上可接受的盐，其制备方法，含有它们的药物组合物及其在治疗中的用途。 本发明特别涉及具有抗肿瘤活性的某些二氢吲哚-2-酮和氮杂 - 二氢吲哚-2-酮，因此可用于人或动物体的治疗方法，特别是这些化合物可用于治疗 涉及异常细胞增殖的病理过程，例如肿瘤生长，类风湿性关节炎，再狭窄和动脉粥样硬化。

公开(公告)号：US07803823B2

公开(公告)日：2010-09-28

申请号：US11742741

申请日：2007-05-01

申请人： Christopher John Love ,  Guy Rosalia Eugeen Van Lommen ,  Julien Georges Pierre-Olivier Doyon ,  Jean-Pierre André Marc Bongartz ,  Marcel Jozef Maria Van der Aa ,  Robert Jozef Maria Hendrickx ,  Peter Jacobus Johannes Antonius Buijnsters ,  Ludwig Paul Cooymans ,  Nele Vandermaesen ,  Erwin Coesemans ,  Gustaaf Maria Boeckx

发明人： Christopher John Love ,  Guy Rosalia Eugeen Van Lommen ,  Julien Georges Pierre-Olivier Doyon ,  Jean-Pierre André Marc Bongartz ,  Marcel Jozef Maria Van der Aa ,  Robert Jozef Maria Hendrickx ,  Peter Jacobus Johannes Antonius Buijnsters ,  Ludwig Paul Cooymans ,  Nele Vandermaesen ,  Erwin Coesemans ,  Gustaaf Maria Boeckx

IPC分类号： A61K31/425 ,  C07D277/20

CPC分类号： C07D417/04 ,  C07D277/42 ,  C07D471/04

摘要： This invention concerns the use of a compound of formula (I′) a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein Z is halo; C1-6alkyl; C1-6alkylcarbonyl; C1-6alkyloxycarbonyl; aminocarbonyl; C1-6alkyl substituted with hydroxy, carboxyl, cyano, amino, amino substituted with piperidinyl, amino substituted with C1-4alkyl substituted piperidinyl, mono- or di(C1-6alkyl)amino, aminocarbonyl, mono- or di(C1-6alkyl)aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkyloxy, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl; polyhaloC1-4alkyl; cyano; amino; mono- or di(C1-6alkyl)aminocarbonyl; C1-6alkyloxycarbonyl; C1-6alkylcarbonyloxy; aminoS(═O)2—; mono- or di(C1-6alkyl)aminoS(═O)2; —C(═N—Rx)NRyRz; Q is optionally substituted C3-6cycloalkyl, phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzthiazolyl, benzoxazolyl, benzimidazolyl, indazolyl, or imidazopyridyl, or Q is a radical of formula L is optionally substituted phenyl or an optionally substituted monocyclic 5 or 6-membered partially saturated or aromatic heterocycle or a bicyclic partially saturated or aromatic heterocycle; aryl is optionally substituted phenyl; for the manufacture of a medicament for the prevention or the treatment of inflammatory and/or auto-immune diseases mediated through TNF-α and/or IL-12.

摘要翻译： 本发明涉及式（I'）化合物的N-氧化物，药学上可接受的加成盐，季胺及其立体化学异构体形式的用途，其中Z为卤素; C 1-6烷基; C 1-6烷基羰基; C 1-6烷氧基羰基; 氨基羰基; 被羟基，羧基，氰基，氨基，被哌啶取代的氨基，被C 1-4烷基取代的哌啶基取代的氨基，单或二（C 1-6烷基）氨基，氨基羰基，一或二（C 1-6烷基）氨基羰基 C 1-6烷氧基羰基，C 1-6烷氧基，哌啶基，哌嗪基，吗啉基，硫代吗啉基; 多卤代C 1-4烷基; 氰基; 氨基; 单或二（C 1-6烷基）氨基羰基; C 1-6烷氧基羰基; C 1-6烷基羰基氧基; 氨基S（= O）2-; 单或二（C 1-6烷基）氨基S（= O）2; -C（= N-Rx）NR y R z; Q是任选取代的C 3-6环烷基，苯基，吡啶基，嘧啶基，吡嗪基，哒嗪基，苯并噻唑基，苯并恶唑基，苯并咪唑基，吲唑基或咪唑并吡啶基，或Q是式L的基团是任选取代的苯基或任选取代的单环5或6- 元部分饱和或芳族杂环或双环部分饱和或芳族杂环; 芳基是任选取代的苯基; 用于制备用于预防或治疗通过TNF-α和/或IL-12介导的炎症和/或自身免疫疾病的药物。

公开(公告)号：US07232838B2

公开(公告)日：2007-06-19

申请号：US10486819

申请日：2002-08-09

申请人： Christopher John Love ,  Guy Rosalia Eugeen Van Lommen ,  Julien Georges Pierre-Olivier Doyon ,  Jean-Pierre André Marc Bongartz ,  Marcel Jozef Maria Van der AA ,  Robert Jozef Maria Hendrickx ,  Peter Jacobus Johannes Antonius Buijnsters ,  Ludwig Paul Cooymans ,  Nele Vandermaesen ,  Erwin Coesemans ,  Gustaaf Maria Boeckx

发明人： Christopher John Love ,  Guy Rosalia Eugeen Van Lommen ,  Julien Georges Pierre-Olivier Doyon ,  Jean-Pierre André Marc Bongartz ,  Marcel Jozef Maria Van der AA ,  Robert Jozef Maria Hendrickx ,  Peter Jacobus Johannes Antonius Buijnsters ,  Ludwig Paul Cooymans ,  Nele Vandermaesen ,  Erwin Coesemans ,  Gustaaf Maria Boeckx

IPC分类号： A61K31/425 ,  C07D277/00 ,  C07D277/20

CPC分类号： C07D417/04 ,  C07D277/42 ,  C07D471/04

摘要： This invention concerns the use of a compound of formula (I′), a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein Z is halo; C1-6alkyl; C1-6alkylcarbonyl; C1-6alkyloxy -carbonyl; aminocarbonyl; C1-6alkyl substituted with hydroxy, carboxyl, cyano, amino, amino substituted with piperidinyl, amino substituted with C1-4alkyl substituted piperidinyl, mono- or di(C1-6alkyl)amino, aminocarbonyl, mono- or di(C1-6alkyl)aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkyloxy, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl; polyhaloC1-4alkyl; cyano; amino; mono- or di(C1-6alkyl)aminocarbonyl; C1-6alkyloxycarbonyl; C1-6alkylcarbonyloxy; aminoS(═O)2—; mono- or di(C1-6alkyl)aminoS(═O)2; —C(═N—Rx)NRyRz; Q is optionally substituted C3-6cycloalkyl, phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzthiazolyl, benzoxazolyl, benzimidazolyl, indazolyl, or imidazopyridyl, or Q is a radical of formula (b-1), (b-2), or (b-3), L is optionally substituted phenyl or an optionally substituted monocyclic 5 or 6-membered partially saturated or aromatic heterocycle or a bicyclic partially saturated or aromatic heterocycle; aryl is optionally substituted phenyl; for the manufacture of a medicament for the prevention or the treatment of inflammatory and/or auto-immune diseases mediated through TNF-α and/or IL-12

摘要翻译： 本发明涉及式（I'）化合物，N-氧化物，药学上可接受的加成盐，季胺及其立体化学异构体形式的用途，其中Z是卤素; C 1-6烷基; C 1-6烷基羰基; C 1-6烷氧基羰基; 氨基羰基; 用羟基，羧基，氰基，氨基，被哌啶取代的氨基，被C 1-4烷基取代的哌啶基取代的氨基，单或二（ C 1-6烷基）氨基，氨基羰基，一或二（C 1-6烷基）氨基羰基，C 1-6烷氧基羰基， C 1-6烷基氧基，哌啶基，哌嗪基，吗啉基，硫代吗啉基; 多卤代1-4烷基; 氰基; 氨基; 单或二（C 1-6烷基）氨基羰基; C 1-6烷氧基羰基; C 1-6烷基羰基氧基; 氨基-S（-O）2 - ; 单或二（C 1-6烷基）氨基S（-O）2; -C（-N-R x X）NR z R z Z; Q为任选取代的C 3-6环烷基，苯基，吡啶基，嘧啶基，吡嗪基，哒嗪基，苯并噻唑基，苯并恶唑基，苯并咪唑基，吲唑基或咪唑并吡啶基，或Q为式（b-1） ，（b-2）或（b-3）中，L是任选取代的苯基或任选取代的单环5或6元部分饱和或芳族杂环或双环部分饱和或芳族杂环; 芳基是任选取代的苯基; 用于制备用于预防或治疗通过TNF-α和/或IL-12介导的炎症和/或自身免疫疾病的药物

公开(公告)号：US20140147386A1

公开(公告)日：2014-05-29

申请号：US14128835

申请日：2012-06-26

申请人： José Ignacio Andrés-Gil ,  Peter Jacobus Johannes Antonius Buijnsters ,  Andrés Avelino Trabanco-Suárez ,  Meri De Angelis ,  Greta Constantia Peter Vanhoof ,  Jérôme Emile Georges Guillemont ,  Frederik Jan Rita Rombouts ,  Maarten Vliegen ,  Guy Maurits R. Bormans ,  SofleJeanne Leopoldine Celens

发明人： José Ignacio Andrés-Gil ,  Peter Jacobus Johannes Antonius Buijnsters ,  Andrés Avelino Trabanco-Suárez ,  Meri De Angelis ,  Greta Constantia Peter Vanhoof ,  Jérôme Emile Georges Guillemont ,  Frederik Jan Rita Rombouts ,  Maarten Vliegen ,  Guy Maurits R. Bormans ,  SofleJeanne Leopoldine Celens

IPC分类号： C07D487/04 ,  G01N33/60 ,  A61K45/06 ,  A61K31/4985 ,  A61K51/04

CPC分类号： C07D487/04 ,  A61K31/4985 ,  A61K45/06 ,  A61K51/0463 ,  G01N33/60

摘要： The present invention relates to novel 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives as inhibitors of phosphodiesterase 2 (PDE2) and to a lesser extent of phosphodiesterase 10 (PDE10) or as inhibitors of both, phosphodiesterases 2 and 10. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which PDE2 is involved, or disorders in which both PDE2 and PDE 10 are involved, such as neurological and psychiatric disorders, and endocrinological or metabolic diseases. The present invention also relates to radiolabelled compounds which may be useful for imaging and quantifying the PDE2 enzyme in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo and to precursors of said compounds.

摘要翻译： 本发明涉及作为磷酸二酯酶2（PDE2）抑制剂的新型1-芳基-4-甲基 - [1,2,4]三唑并[4,3-a] - 喹喔啉衍生物和较少程度的磷酸二酯酶10（PDE10 ）或作为磷酸二酯酶2和10两者的抑制剂。本发明还涉及包含这些化合物的药物组合物，制备此类化合物和组合物的方法，以及用于预防和治疗疾病的化合物和组合物 涉及PDE2或PDE2和PDE10两者涉及的疾病，如神经和精神疾病，以及内分泌或代谢疾病。 本发明还涉及放射性标记的化合物，其可用于使用正电子发射断层摄影（PET）在组织中成像和定量PDE2酶。 本发明还涉及包含这些化合物的组合物，用于制备此类化合物和组合物的方法，以使用这些化合物和组合物用于在体外或体内成像组织，细胞或宿主以及所述化合物的前体。

公开(公告)号：US10604523B2

公开(公告)日：2020-03-31

申请号：US14128835

申请日：2012-06-26

申请人： José Ignacio Andrés-Gil ,  Peter Jacobus Johannes Antonius Buijnsters ,  Andrés Avelino Trabanco-Suárez ,  Meri De Angelis ,  Greta Constantia Peter Vanhoof ,  Jérôme Emile Georges Guillemont ,  Frederik Jan Rita Rombouts ,  Maarten Vliegen ,  Guy Maurits R. Bormans ,  Sofie Jeanne Leopoldine Celen

发明人： José Ignacio Andrés-Gil ,  Peter Jacobus Johannes Antonius Buijnsters ,  Andrés Avelino Trabanco-Suárez ,  Meri De Angelis ,  Greta Constantia Peter Vanhoof ,  Jérôme Emile Georges Guillemont ,  Frederik Jan Rita Rombouts ,  Maarten Vliegen ,  Guy Maurits R. Bormans ,  Sofie Jeanne Leopoldine Celen

IPC分类号： A61K51/00 ,  A61M36/14 ,  C07D487/04 ,  A61K31/4985 ,  A61K45/06 ,  A61K51/04 ,  G01N33/60

摘要： The present invention relates to novel 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives as inhibitors of phosphodiesterase 2 (PDE2) and to a lesser extent of phosphodiesterase 10 (PDE10) or as inhibitors of both, phosphodiesterases 2 and 10. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which PDE2 is involved, or disorders in which both PDE2 and PDE10 are involved, such as neurological and psychiatric disorders, and endocrinological or metabolic diseases. The present invention also relates to radiolabelled compounds which may be useful for imaging and quantifying the PDE2 enzyme in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo and to precursors of said compounds.