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    Benzisoxazole derivatives
    3.
    发明授权
    Benzisoxazole derivatives 有权
    苯并异恶唑衍生物

    公开(公告)号：US08816090B2

    公开(公告)日：2014-08-26

    申请号：US11814588

    申请日：2006-02-15

    Applicant: Hirohide Noguchi ,  Isao Sakurada ,  Chikara Uchida ,  Nobuaki Waizumi

    Inventor： Hirohide Noguchi ,  Isao Sakurada ,  Chikara Uchida ,  Nobuaki Waizumi

    IPC: C07D261/20 ,  A61K31/4439

    CPC classification number: C07D413/12 ,  C07D413/14

    Abstract: This invention relates to compounds of the formula (I): wherein A, B, R1, R4, m, and n are each as described herein or a pharmaceutically acceptable salt thereof, and compositions containing such compounds and the use of such compounds in the treatment of a condition mediated by 5-HT4 receptor activity such as, but not limited to, gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central 10 nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders such as cardiac failure and heart arrhythmia, diabetes and apnea syndrome.

    Abstract translation: 本发明涉及式（I）的化合物：其中A，B，R 1，R 4，m和n各自如本文所述或其药学上可接受的盐，以及含有这些化合物的组合物和这些化合物在 治疗由5-HT4受体活性介导的病症，例如但不限于胃食管反流病，胃肠道疾病，胃动力障碍，非溃疡性消化不良，功能性消化不良，肠易激综合征（IBS），便秘，消化不良，食管炎 ，胃肠疾病，恶心，中枢10神经系统疾病，阿尔茨海默病，认知障碍，呕吐，偏头痛，神经系统疾病，疼痛，心力衰竭和心律失常等心血管疾病，糖尿病和呼吸暂停综合征。

    Imidazopyridine compounds as 5-HT4 receptor modulators
    5.
    发明授权
    Imidazopyridine compounds as 5-HT4 receptor modulators 失效
    咪唑并吡啶化合物作为5-HT4受体调节剂

    公开(公告)号：US06624162B2

    公开(公告)日：2003-09-23

    申请号：US10251109

    申请日：2002-09-20

    Applicant: Chikara Uchida ,  Hirohide Noguchi ,  Alan Stobie ,  Geoffrey Gymer ,  David Fenwick

    Inventor： Chikara Uchida ,  Hirohide Noguchi ,  Alan Stobie ,  Geoffrey Gymer ,  David Fenwick

    IPC: A61K31437

    CPC classification number: C07D471/04

    Abstract: This invention provides a compound of the formula (I): or the pharmaceutically acceptable salts thereof wherein R1 is hydrogen, halo or alkyl; R2 and R3 are independently hydrogen, alkyl, alkenyl, alkynyl, aminoalkyl or hydroxyalkyl; or R2 and R3 taken together with the nitrogen atom to which they are attached may form hetrocyclic; R4 is hydrogen, halo, acyl, amino, amido, aryl, arylalkyl, or heteroaryl; R5 is hydrogen, halo, alkyl alkenyl, alkynyl, acyl, amino, amido, aryl, arylalkyl, or heteroaryl; R6 is hydrogen, alkyl or alkoxyalkyl; X is NR9 wherein R9 is hydrogen or alkyl; and Y is (CR7R8)n wherein n is an integer from 0 to 5. These compounds have 5-HT4 receptor binding activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, Functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans. This invention also provides a pharmaceutical composition comprising the above compound.

    Abstract translation: 本发明提供式（I）化合物或其药学上可接受的盐，其中R 1是氢，卤素或烷基; R 2和R 3独立地是氢，烷基，烯基，炔基，氨基烷基或羟烷基; 或R 2和R 3与它们所连接的氮原子一起可以形成环状的; R 4是氢，卤素，酰基，氨基，酰氨基，芳基，芳基烷基或杂芳基; R 5是氢，卤素，烷基烯基，炔基，酰基，氨基，酰氨基，芳基，芳基烷基或杂芳基; R 6是氢，烷基或烷氧基烷基; X是NR 9，其中R 9是氢或烷基; 并且Y是（CR 7 R 8）n，其中n是0至5的整数。这些化合物具有5-HT 4受体结合活性，因此可用于治疗胃食管反流病，非溃疡性消化不良 ，功能性消化不良，肠易激综合征等。 本发明还提供了包含上述化合物的药物组合物。

    Benzisoxazole Derivatives
    7.
    发明申请
    Benzisoxazole Derivatives 有权
    苯并异恶唑衍生物

    公开(公告)号：US20080207690A1

    公开(公告)日：2008-08-28

    申请号：US11814588

    申请日：2006-02-15

    Applicant: Hirohide Noguchi ,  Isao Sakurada ,  Chikara Uchida ,  Nobuaki Waizumi

    Inventor： Hirohide Noguchi ,  Isao Sakurada ,  Chikara Uchida ,  Nobuaki Waizumi

    IPC: A61K31/454 ,  C07D401/12 ,  A61P1/04 ,  C07D401/14

    CPC classification number: C07D413/12 ,  C07D413/14

    Abstract: This invention relates to compounds of the formula (I): wherein A, B, R1, R4, m, and n are each as described herein or a pharmaceutically acceptable salt thereof, and compositions containing such compounds and the use of such compounds in the treatment of a condition mediated by 5-HT4 receptor activity such as, but not limited to, gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central 10 nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders such as cardiac failure and heart arrhythmia, diabetes and apnea syndrome.

    Abstract translation: 本发明涉及式（I）化合物：其中A，B，R 1，R 4，m和n各自如本文所述，或药学上可接受的 其盐和含有这些化合物的组合物以及这些化合物在治疗5-HT 4受体活性介导的病症中的用途，例如但不限于胃食管反流病，胃肠道疾病， 胃动力障碍，非溃疡性消化不良，功能性消化不良，肠易激综合征（IBS），便秘，消化不良，食管炎，胃食管疾病，恶心，中枢10神经系统疾病，阿尔茨海默病，认知障碍，呕吐，偏头痛，神经系统疾病，疼痛 ，心血管疾病如心力衰竭和心律失常，糖尿病和呼吸暂停综合征。

    Imidazopyridine compounds as 5-HT4 receptor agonists
    8.
    发明授权
    Imidazopyridine compounds as 5-HT4 receptor agonists 失效
    咪唑并吡啶化合物作为5-HT4受体激动剂

    公开(公告)号：US07012080B2

    公开(公告)日：2006-03-14

    申请号：US10667188

    申请日：2003-09-17

    Applicant: Satoru Iguchi ,  Yasuhiro Katsu ,  Kana Kon-I ,  Hirohide Noguchi ,  Chikara Uchida

    Inventor： Satoru Iguchi ,  Yasuhiro Katsu ,  Kana Kon-I ,  Hirohide Noguchi ,  Chikara Uchida

    IPC: A61K31/437 ,  C07D471/04 ,  A61P1/04

    CPC classification number: C07D471/04

    Abstract: This invention provides a compound of the formula (I): or a pharmaceutically acceptable salt thereof, wherein R1 represents a hydrogen atom or a halogen atom; R2 represents a methyl group or an ethyl group; R3 represents a branched alkyl group having from 3 to 6 carbon atoms or an alkyl group having from 3 to 6 carbon atoms substituted by an alkoxy group having from 1 to 6 carbon atoms; with the proviso that when the terminal carbon atom of said alkyl group of R3 is substituted by said alkoxy group, said alkyl group is a branched alkyl group. These compounds have 5-HT4 receptor binding activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans. This invention also provides a pharmaceutical composition comprising the above compound.

    Abstract translation: 本发明提供式（I）化合物或其药学上可接受的盐，其中R 1表示氢原子或卤素原子; R 2表示甲基或乙基; R 3表示具有3至6个碳原子的支链烷基或具有3至6个碳原子的烷基，被具有1至6个碳原子的烷氧基取代; 条件是当所述R 3烷基的末端碳原子被所述烷氧基取代时，所述烷基是支链烷基。 这些化合物具有5-HT 4受体结合活性，因此可用于治疗哺乳动物，特别是人类中的胃食管反流病，非溃疡性消化不良，功能性消化不良，肠易激综合征等。 本发明还提供了包含上述化合物的药物组合物。

    2-substituted-1-piperidyl benzimidazole compounds as ORL1-receptor agonists
    9.
    发明授权
    2-substituted-1-piperidyl benzimidazole compounds as ORL1-receptor agonists 失效
    2-取代-1-哌啶基苯并咪唑化合物作为ORL1-受体激动剂

    公开(公告)号：US06172067B2

    公开(公告)日：2001-01-09

    申请号：US09369208

    申请日：1999-08-05

    Applicant: Fumitaka Ito ,  Hirohide Noguchi ,  Hiroshi Kondo

    Inventor： Fumitaka Ito ,  Hirohide Noguchi ,  Hiroshi Kondo

    IPC: A61K31454

    CPC classification number: C07D401/04 ,  C07D211/58 ,  C07D401/14

    Abstract: A compound of the formula: or a pharmaceutically acceptable salt thereof, wherein R is unsubstituted, mono-, di- or tri-substituted (C3-C11)cycloalkyl or (C3-C11)cycloalkenyl or the like, A is unsubstituted (C1-C7)alkyl or (C2-C5 )alkenyl, or unsubstituted, mono-, di- or tri-substituted aryl, or aromatic-heterocyclic or the like, Y is hydrogen, halo, amino or mercapto, or unsubstituted, mono-, di- or tri- substituted (C1-C10)alkyl-M—, (C3-C7)cycloalkyl-M—, (C2-C6)alkenyl-M—, (C1-C4)alkyl-NH-((C1-C4)alkyl)-M—, di(C1-C4)alkyl-N-((C1-C4)alkyl)-M—, aryl-M—, aromatic or non-aromatic heterocyclic-M—, aryl-(C1-C5)alkyl-M— or aromatic non-aromatic heterocyclic-(C1-C5)alkyl-M—, wherein M is a covalent bond O, S, NH or the like, or the like; Z1, Z2, Z3 and Z4 are hydrogen or the like, has ORL1-receptor agonist activity, and are useful as analgesics or the like in mammalian subjects.

    Abstract translation: 一种下式的化合物或其药学上可接受的盐，其中R是未取代的一价，二或三取代的（C 3 -C 11）环烷基或（C 3 -C 11）环烯基等，A是未取代的（C1- C7）烷基或（C2-C5）烯基或未取代的单，二或三取代的芳基或芳族杂环等，Y是氢，卤素，氨基或巯基，或未取代的单，二 - （C 1 -C 6）烷基-M-，（C 3 -C 7）环烷基M - ，（C 2 -C 6）烯基-M-，（C 1 -C 4）烷基-NH-（（C 1 -C 4） 烷基）-M-，二（C 1 -C 4）烷基-N - （（C 1 -C 4）烷基）-M-，芳基M-，芳族或非芳族杂环M-，芳基 - （C 1 -C 5） 烷基-M-或芳族非芳族杂环 - （C1-C5）烷基-M-，其中M是共价键O，S，NH等; Z1，Z2，Z3和Z4为氢等具有ORL1-受体激动剂活性，并且可用作哺乳动物受试者中的止痛剂等。

    Polymorph Form of 4-methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid
    10.
    发明申请
    Polymorph Form of 4-methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid 有权
    4-甲基）哌啶-1-基]甲基} - 四氢-2H-吡喃-4-羧酸的多晶型

    公开(公告)号：US20140187583A1

    公开(公告)日：2014-07-03

    申请号：US14118377

    申请日：2012-05-18

    Applicant: Toyoharu Numata ,  Hirohide Noguchi ,  Nobuaki Waizumi ,  Takashi Kojima

    Inventor： Toyoharu Numata ,  Hirohide Noguchi ,  Nobuaki Waizumi ,  Takashi Kojima

    IPC: C07D413/14

    CPC classification number: C07D413/14

    Abstract: The present invention relates to novel crystal forms of 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid. More particularly, the invention relates to polymorph forms (Polymorph Form I or Polymorph Form II), and to processes for the preparation of, compositions containing and to uses of, such polymorph forms.

    Abstract translation: 本发明涉及4 - {[4 - （{[4-（2,2,2-三氟乙氧基）-1,2-苯并异恶唑-3-基]氧基}甲基）哌啶-1-基] 甲基} - 四氢-2H-吡喃-4-羧酸。 更具体地说，本发明涉及多晶型形式（多晶型I或多晶型II），以及制备含这种多晶型形式的组合物和使用方法。

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