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11. 发明授权

US07790727B2 Benzenesulfonanilide compounds suitable for treating disorders that respond to modulation of the serotonin 5-HT6 receptor 有权
标题翻译：苯磺酰苯胺化合物适用于治疗对血清素5-HT6受体调节作用的疾病
公开(公告)号：US07790727B2
公开(公告)日：2010-09-07
申请号：US12262455
申请日：2008-10-31
申请人： Wilfried Martin Braje , Sean Colm Turner , Andreas Haupt , Udo Lange , Karla Drescher , Karsten Wicke , Liliane Unger , Mario Mezler , Wolfgang Wernet , Matthias Mayrer , Ana Jongen-Relo , Anton Bespalov , Min Zhang
发明人： Wilfried Martin Braje , Sean Colm Turner , Andreas Haupt , Udo Lange , Karla Drescher , Karsten Wicke , Liliane Unger , Mario Mezler , Wolfgang Wernet , Matthias Mayrer , Ana Jongen-Relo , Anton Bespalov , Min Zhang
IPC分类号： A61K31/495 , A61K31/496 , C07D295/135 , C07D317/62
CPC分类号： C07D295/12 , C07D405/12
摘要： The present invention relates to novel benzenesulfonanilide compounds of the formulae I and I′ and physiologically tolerated acid addition salts and the N-oxides thereof. The compounds possess valuable therapeutic properties and are particularly suitable, for treating diseases that respond to modulation of the serotonin 5-HT6 receptor. wherein R1 is hydrogen or methyl R2 is hydrogen or methyl R3 hydrogen, fluorine C1-C2 alkoxy or fluorinated C1-C2 alkoxy; R4 is hydrogen, C1-C4 alkyl or fluorinated C1-C4 alkyl; R5 is hydrogen, fluorine, C1-C2 alkyl, fluorinated C1-C2 alkyl, C1-C2 alkoxy or fluorinated C1-C2 alkoxy; and R6 is hydrogen, fluorine or chlorine.
摘要翻译：本发明涉及式I和I'的新型苯磺酰苯胺化合物和生理上耐受的酸加成盐及其N-氧化物。该化合物具有有价值的治疗特性，特别适用于治疗对血清素5-HT 6受体调节作出反应的疾病。其中R1是氢或甲基R2是氢或甲基R3氢，氟C1-C2烷氧基或氟化C1-C2烷氧基; R4是氢，C1-C4烷基或氟化C1-C4烷基; R5是氢，氟，C1-C2烷基，氟化C1-C2烷基，C1-C2烷氧基或氟化C1-C2烷氧基; R6是氢，氟或氯。

12. 发明授权

US08653100B2 Tetrahydroisoquinolines, pharmaceutical compositions containing them, and their use in therapy 有权
标题翻译：四氢异喹啉，含有它们的药物组合物及其在治疗中的应用
公开(公告)号：US08653100B2
公开(公告)日：2014-02-18
申请号：US12933326
申请日：2009-03-31
申请人： Michael Ochse , Udo Lange , Wilfried Braje , Berthold Behl , Wilfried Hornberger , Mario Mezler , Wilhelm Amberg , Charles W. Hutchins
发明人： Michael Ochse , Udo Lange , Wilfried Braje , Berthold Behl , Wilfried Hornberger , Mario Mezler , Wilhelm Amberg , Charles W. Hutchins
IPC分类号： C07D217/00 , A61K31/472
CPC分类号： C07D217/18 , C07D401/04 , C07D401/06 , C07D401/08 , C07D401/12 , C07D409/12 , C07D409/14 , C07D413/12 , C07D413/14 , C07D417/12 , C07D498/04 , C07D513/04
摘要： The present invention relates to tetrahydroisoquinoline of the formula (I) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such tetrahydroisoquinolines, and the use of such tetrahydroisoquinolines for therapeutic purposes. The tetrahydroisoquinolines are GlyT1 inhibitors.
摘要翻译：本发明涉及式（I）的四氢异喹啉或其生理上耐受的盐。本发明涉及包含这种四氢异喹啉的药物组合物以及用于治疗目的的这种四氢异喹啉的用途。四氢异喹啉是GlyT1抑制剂。

13. 发明申请

US20130203749A1 Tetrahydroisoquinolines, pharmaceutical compositions containing them, and their use in therapy 有权
公开(公告)号：US20130203749A1
公开(公告)日：2013-08-08
申请号：US13792105
申请日：2013-03-10
申请人： Wilhelm Amberg , Michael Ochse , Udo Lange , Wilfried Braje , Berthold Behl , Wilfried Hornberger , Mario Mezler , Charles Hutchins
发明人： Wilhelm Amberg , Michael Ochse , Udo Lange , Wilfried Braje , Berthold Behl , Wilfried Hornberger , Mario Mezler , Charles Hutchins
IPC分类号： C07D217/18 , C07D409/12 , C07D401/04 , C07D401/08 , C07D513/04 , C07D498/04 , C07D401/12 , C07D413/14
CPC分类号： C07D217/18 , C07D401/04 , C07D401/06 , C07D401/08 , C07D401/12 , C07D409/12 , C07D409/14 , C07D413/12 , C07D413/14 , C07D417/12 , C07D498/04 , C07D513/04
摘要： The present invention relates to tetrahydroisoquinoline of the formula (I) or a physiologically tolerated salt thereof.The invention relates to pharmaceutical compositions comprising such tetrahydroisoquinolines, and the use of such tetrahydroisoquinolines for therapeutic purposes. The tetrahydroisoquinolines are GlyT1 inhibitors.

14. 发明申请

US20110105502A1 TETRAHYDROISOQUINOLINES, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND THEIR USE IN THERAPY 有权
标题翻译：四氢喹诺酮类，含有它们的药物组合物及其在治疗中的使用
公开(公告)号：US20110105502A1
公开(公告)日：2011-05-05
申请号：US12933326
申请日：2009-03-31
申请人： Wilhelm Amberg , Michael Ochse , Udo Lange , Wilfried Braje , Berthold Behl , Wilfried Hornberger , Mario Mezler , Charles W. Hutchins
发明人： Wilhelm Amberg , Michael Ochse , Udo Lange , Wilfried Braje , Berthold Behl , Wilfried Hornberger , Mario Mezler , Charles W. Hutchins
IPC分类号： A61K31/5377 , C07D217/00 , C07D413/12 , A61K31/47 , A61P25/18 , A61P25/24
CPC分类号： C07D217/18 , C07D401/04 , C07D401/06 , C07D401/08 , C07D401/12 , C07D409/12 , C07D409/14 , C07D413/12 , C07D413/14 , C07D417/12 , C07D498/04 , C07D513/04
摘要： The present invention relates to tetrahydroisoquinoline of the formula (I) or a physiologically tolerated salt thereof.The invention relates to pharmaceutical compositions comprising such tetrahydroisoquinolines, and the use of such tetrahydroisoquinolines for therapeutic purposes. The tetrahydroisoquinolines are GlyT1 inhibitors.
摘要翻译：本发明涉及式（I）的四氢异喹啉或其生理上耐受的盐。本发明涉及包含这种四氢异喹啉的药物组合物以及用于治疗目的的这种四氢异喹啉的用途。四氢异喹啉是GlyT1抑制剂。

15. 发明授权

US08420670B2 4-benzylaminoquinolines, pharmaceutical compositions containing them, and their use in therapy 有权
标题翻译： 4-苄基氨基喹啉，含有它们的药物组合物及其在治疗中的用途
公开(公告)号：US08420670B2
公开(公告)日：2013-04-16
申请号：US12666629
申请日：2008-08-22
申请人： Wilhelm Amberg , Michael Ochse , Wilfried Braje , Berthold Behl , Wilfried Hornberger , Mario Mezler , Charles W. Hutchins
发明人： Wilhelm Amberg , Michael Ochse , Wilfried Braje , Berthold Behl , Wilfried Hornberger , Mario Mezler , Charles W. Hutchins
IPC分类号： A61K31/04 , C07D215/38
CPC分类号： C07D215/42 , C07D215/46 , C07D401/12 , C07D401/14
摘要： The present invention relates to 4-benzylaminoquinolines of the formula (I) or physiologically tolerated salts thereof. The invention relates to pharmaceutical compositions comprising such quinolines, and the use of such quinolines for therapeutic purposes. The quinolines are GIyTI inhibitors.
摘要翻译：本发明涉及式（I）的4-苄基氨基喹啉或其生理上耐受的盐。本发明涉及包含这种喹啉的药物组合物，以及这些喹啉用于治疗目的的用途。喹啉是GlyTI抑制剂。

16. 发明申请

US20110245247A1 NOVEL SMALL MOLECULE POTENTIATORS OF METABOTROPIC GLUTAMATE RECEPTORS 有权
公开(公告)号：US20110245247A1
公开(公告)日：2011-10-06
申请号：US13073087
申请日：2011-03-28
申请人： Wilfried Braje , Katja Jantos , Hervé Geneste , Mario Mezler , Margaretha Henrica Maria Bakker
发明人： Wilfried Braje , Katja Jantos , Hervé Geneste , Mario Mezler , Margaretha Henrica Maria Bakker
IPC分类号： A61K31/5377 , C07D401/12 , C07D401/14 , C07D413/14 , C07D403/12 , A61K31/4439 , A61K31/496 , A61K31/4725 , A61K31/497 , A61K31/4709 , A61K31/498 , A61P25/00 , A61P25/18 , A61P25/22 , A61P25/24 , A61P25/08 , A61P25/06
CPC分类号： C07D401/12 , C07D401/14 , C07D403/12 , C07D413/12 , C07D413/14
摘要： The present invention relates to small molecule potentiators of metabotropic receptors, in particular of the mGlu2 receptor. The present invention also relates to the use of these compounds for the prevention or treatment of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The present invention thus provides compounds of formula I wherein X1 is N or C—R1, X2 is N or C—R2, X3 is N or C—R3, X4 is N or C—R4 provided that none or one of X1, X2, X3 or X4 is N; Y1 is N, C or C—R5, Y2 is N, C or C—R6, Y3 is Y1, Y2, N, C or C—R7, Y4 is N, C or C—R8 provided that only the moiety Y1, Y2, Y3 or Y4 to which Z is bound is C and further provided at most one of Y1, Y2, Y3 or Y4 is N; Z is O, S, S(O), S(O)2 or NRZ; Q is CH2 or CH2CH2, where one or two of the hydrogen atoms in CH2 or CH2CH2 may be replaced by halogen, C1-C4-alkyl or C1-C4-haloalkyl; R1 is inter alia hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C4-haloalkoxy, C3-C8-cycloalkyl, a radical NR1aR1b, C-bound 3- to 7-membered, saturated heterocyclyl having 1 or 2 nitrogen atoms and 0 or 1 heteroatoms, selected from O and S, as ring members, aryl, aryl-CH2, aryloxy, hetaryl, hetaryloxy or hetaryl-CH2, wherein the heterocyclyl, aryl and hetaryl rings ring in the last six radicals themselves are unsubstituted or carry 1, 2, 3, 4 or 5 identical or different radicals R1c; R2 has one of the meanings given for R1; R3 and R4 are, inter alia, selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkyl, phenyl, C1-C4-haloalkoxy, a radical (CH2)nNR′R″; R5, R6, R7, R8 are, independently of each other, selected from hydrogen, halogen, etc.; Ra is C3-C6-cycloalkyl, C1-C6-haloalkyl or C1-C6-alkyl, which is unsubstituted or carries one radical selected from C1-C4-alkoxy, C1-C4-haloalkoxy and a radical NRa1Ra2; and the N-oxides and the pharmaceutically acceptable salts thereof.

17. 发明授权

US09242933B2 Heterocyclic compounds as positive modulators of metabotropic glutamate receptor 2 (mGlu2 receptor) 有权
标题翻译：杂环化合物作为代谢型谷氨酸受体2（mGlu2受体）的阳性调节剂
公开(公告)号：US09242933B2
公开(公告)日：2016-01-26
申请号：US12126174
申请日：2008-05-23
申请人： Herve Geneste , Daryl Sauer , Wilfried Braje , Wilhelm Amberg , Mario Mezler , Margaretha Henrica Maria Bakker
发明人： Herve Geneste , Daryl Sauer , Wilfried Braje , Wilhelm Amberg , Mario Mezler , Margaretha Henrica Maria Bakker
IPC分类号： C07D207/335 , C07D409/06 , C07D215/12 , C07D231/12 , A61K31/44 , C07D209/14 , C07D209/26 , C07D213/36 , C07D213/38 , C07D233/58 , C07D239/26 , C07D261/08 , C07D277/28 , C07D307/14 , C07D307/54 , C07D333/20 , C07D333/58 , C07D407/04 , C07D409/04
CPC分类号： C07D209/14 , C07D207/335 , C07D209/26 , C07D213/36 , C07D213/38 , C07D215/12 , C07D231/12 , C07D233/58 , C07D239/26 , C07D261/08 , C07D277/28 , C07D307/14 , C07D307/54 , C07D333/20 , C07D333/58 , C07D407/04 , C07D409/04 , C07D409/06
摘要： The present invention relates to heterocyclic compounds which are positive modulators of metabotropic glutamate receptor. The present invention also relates to the use of these compounds for preparing a pharmaceutical composition and to a method of treating a medical disorder, selected from neurological and psychiatric disorders associated with glutamate dysfunction.
摘要翻译：本发明涉及作为代谢型谷氨酸受体的阳性调节剂的杂环化合物。本发明还涉及这些化合物用于制备药物组合物和治疗选自与谷氨酸功能障碍相关的神经和精神障碍的医学病症的方法的用途。

18. 发明授权

US08664214B2 Small molecule potentiators of metabotropic glutamate receptors I 有权
标题翻译：代谢型谷氨酸受体的小分子增效剂I
公开(公告)号：US08664214B2
公开(公告)日：2014-03-04
申请号：US13071753
申请日：2011-03-25
申请人： Wilfried Braje , Katja Jantos , Hervé Geneste , Mario Mezler , Margaretha Henrica Maria Bakker , Jayne Froggett
发明人： Wilfried Braje , Katja Jantos , Hervé Geneste , Mario Mezler , Margaretha Henrica Maria Bakker , Jayne Froggett
IPC分类号： C07D231/12 , C07D409/04 , A61K31/4164
CPC分类号： C07D401/12 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/14 , C07D413/14
摘要： The present invention relates to small molecule potentiators of metabotropic receptors, in particular of the mGlu2 receptor. The present invention also relates to the use of these compounds for the prevention or treatment of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The present invention thus provides compounds of formula I and variables defined herein.
摘要翻译：本发明涉及代谢型受体特别是mGlu2受体的小分子增效剂。本发明还涉及这些化合物用于预防或治疗与谷氨酸功能障碍相关的神经和精神疾病以及涉及代谢型谷氨酸受体的疾病的用途。因此，本发明提供式I化合物和本文定义的变量。

19. 发明授权

US08314120B2 Small molecule potentiators of metabotropic glutamate receptors 有权
公开(公告)号：US08314120B2
公开(公告)日：2012-11-20
申请号：US13073087
申请日：2011-03-28
申请人： Wilfried Braje , Katja Jantos , Hervé Geneste , Mario Mezler , Margaretha Henrica Maria Bakker
发明人： Wilfried Braje , Katja Jantos , Hervé Geneste , Mario Mezler , Margaretha Henrica Maria Bakker
IPC分类号： A61K31/4375 , A61K31/4725 , A61K31/403 , C07D471/04 , C07D217/22 , C07D487/04 , C07D209/46
CPC分类号： C07D401/12 , C07D401/14 , C07D403/12 , C07D413/12 , C07D413/14
摘要： The present invention relates to small molecule potentiators of metabotropic receptors, in particular of the mGlu2 receptor. The present invention also relates to the use of these compounds for the prevention or treatment of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The present invention thus provides compounds of formula I wherein X1 is N or C—R1, X2 is N or C—R2, X3 is N or C—R3, X4 is N or C—R4 provided that none or one of X1, X2, X3 or X4 is N; Y1 is N, C or C—R5, Y2 is N, C or C—R6, Y3 is Y1, Y2, N, C or C—R7, Y4 is N, C or C—R8 provided that only the moiety Y1, Y2, Y3 or Y4 to which Z is bound is C and further provided at most one of Y1, Y2, Y3 or Y4 is N; Z is O, S, S(O), S(O)2 or NRZ; Q is CH2 or CH2CH2, where one or two of the hydrogen atoms in CH2 or CH2CH2 may be replaced by halogen, C1-C4-alkyl or C1-C4-haloalkyl; R1 is inter alia hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C4-haloalkoxy, C3-C8-cycloalkyl, a radical NR1aR1b, C-bound 3- to 7-membered, saturated heterocyclyl having 1 or 2 nitrogen atoms and 0 or 1 heteroatoms, selected from O and S, as ring members, aryl, aryl-CH2, aryloxy, hetaryl, hetaryloxy or hetaryl-CH2, wherein the heterocyclyl, aryl and hetaryl rings ring in the last six radicals themselves are unsubstituted or carry 1, 2, 3, 4 or 5 identical or different radicals R1c; R2 has one of the meanings given for R1; R3 and R4 are, inter alia, selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkyl, phenyl, C1-C4-haloalkoxy, a radical (CH2)nNR′R″; R5, R6, R7, R8 are, independently of each other, selected from hydrogen, halogen, etc.; Ra is C3-C6-cycloalkyl, C1-C6-haloalkyl or C1-C6-alkyl, which is unsubstituted or carries one radical selected from C1-C4-alkoxy, C1-C4-haloalkoxy and a radical NRa1Ra2; and the N-oxides and the pharmaceutically acceptable salts thereof.

20. 发明申请

US20110245232A1 NOVEL SMALL MOLECULE POTENTIATORS OF METABOTROPIC GLUTAMATE RECEPTORS I 有权
公开(公告)号：US20110245232A1
公开(公告)日：2011-10-06
申请号：US13071753
申请日：2011-03-25
申请人： Wilfried Braje , Katja Jantos , Hervé Geneste , Mario Mezler , Margaretha Henrica Maria Bakker , Jayne Froggett
发明人： Wilfried Braje , Katja Jantos , Hervé Geneste , Mario Mezler , Margaretha Henrica Maria Bakker , Jayne Froggett
IPC分类号： A61K31/553 , C07D401/12 , A61K31/4439 , C07D413/14 , A61K31/5377 , C07D401/14 , A61K31/496 , A61P25/00 , A61P25/18 , A61P25/24 , A61P25/08 , A61P25/06
CPC分类号： C07D401/12 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/14 , C07D413/14
摘要： The present invention relates to small molecule potentiators of metabotropic receptors, in particular of the mGlu2 receptor. The present invention also relates to the use of these compounds for the prevention or treatment of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The present invention thus provides compounds of formula I wherein X2 is N or C—R2, X3 is N or C—R3, X4 is N or C—R4 provided that none or one of X2, X3 or X4 is N; Y1 is N, C or C—R5, Y2 is N, C or C—R6, Y3 is N, C or C—R7, Y4 is N, C or C—R8 provided that only the moiety Y1, Y2, Y3 or Y4 to which Z is bound is C and further provided at most one of Y1, Y2, Y3 or Y4 is N; Z is O, S, S(O), S(O)2 or NRZ; Q is CH2 or CH2CH2, where one or two of the hydrogen atoms in CH2 or CH2CH2 may be replaced by halogen, C1-C4-alkyl or C1-C4-haloalkyl; R1 is inter alia hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C4-haloalkoxy, C3-C8-cycloalkyl, a radical NR1aR1b, C-bound 3- to 7-membered, saturated heterocyclyl having 1 or 2 nitrogen atoms and 0 or 1 heteroatoms, selected from O and S, as ring members, aryl, aryl-CH2, aryloxy, hetaryl, hetaryloxy or hetaryl-CH2, wherein the heterocyclyl, aryl and hetaryl rings ring in the last six radicals themselves are unsubstituted or carry 1, 2, 3, 4 or 5 identical or different radicals R1c; R2, R3 and R4 are, inter alia, selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkyl, phenyl, C1-C4-haloalkoxy, a radical (CH2)nNR′R″; R5, R6, R7, R8 are, independently of each other, selected from hydrogen, halogen, etc.; Ra is C3-C6-cycloalkyl, C1-C6-haloalkyl or C1-C6-alkyl, which is unsubstituted or carries one radical selected from C1-C4-alkoxy, C1-C4-haloalkoxy and a radical NRa1Ra2, Rb is hydrogen, halogen or C1-C4-alkyl; and the N-oxides and the pharmaceutically acceptable salts thereof.

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