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    Inhibitors of D-amino acid oxidase
    1.
    发明授权
    Inhibitors of D-amino acid oxidase 有权
    D-氨基酸氧化酶抑制剂

    公开(公告)号：US07902252B2

    公开(公告)日：2011-03-08

    申请号：US12506204

    申请日：2009-07-20

    申请人： Michele L. R. Heffernan ,  Qun Kevin Fang ,  Robert J. Foglesong ,  Seth C. Hopkins ,  Cyprian O. Ogbu ,  Mustapha Soukri ,  Kerry L. Spear

    发明人： Michele L. R. Heffernan ,  Qun Kevin Fang ,  Robert J. Foglesong ,  Seth C. Hopkins ,  Cyprian O. Ogbu ,  Mustapha Soukri ,  Kerry L. Spear

    IPC分类号： A61K31/403 ,  C07D209/02

    CPC分类号： C07D209/42 ,  C07D209/52 ,  C07D209/94 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04

    摘要： The present invention provides novel inhibitors of the enzyme D-amino acid oxidase. The compounds of the invention are useful for treating or preventing diseases and/or condition, wherein modulation of D-serine levels, and/or its oxidative products, is effective in ameliorating symptoms. The invention further provides methods of enhancing learning, memory and/or cognition. For example, the invention provides methods for treating or preventing loss of memory and/or cognition associated with neurodegenerative diseases, such as Alzheimer's disease. The invention further provides methods for preventing loss of neuronal function characteristic of neurodegenerative diseases. In addition, methods are provided for the treatment or prevention of neuropsychiatric diseases (e.g., schizophrenia) and for the treatment or prevention of pain and ataxia.

    摘要翻译： 本发明提供D-氨基酸氧化酶酶的新型抑制剂。 本发明的化合物可用于治疗或预防疾病和/或病症，其中D-丝氨酸水平和/或其氧化产物的调节在改善症状中是有效的。 本发明还提供增强学习，记忆和/或认知的方法。 例如，本发明提供了治疗或预防与神经变性疾病如阿尔茨海默病有关的记忆丧失和/或认知丧失的方法。 本发明还提供了用于预防神经变性疾病的神经元功能特征丧失的方法。 此外，提供了用于治疗或预防神经精神疾病（例如精神分裂症）和用于治疗或预防疼痛和共济失调的方法。

    INHIBITORS OF D-AMINO ACID OXIDASE
    4.
    发明申请
    INHIBITORS OF D-AMINO ACID OXIDASE 有权
    D-氨基酸氧化酶的抑制剂

    公开(公告)号：US20100029737A1

    公开(公告)日：2010-02-04

    申请号：US12506204

    申请日：2009-07-20

    申请人： Michele L. R. Heffernan ,  Qun Kevin Fang ,  Robert J. Foglesong ,  Seth C. Hopkins ,  Cyprian O. Ogbu ,  Mustapha Soukri ,  Kerry L. Spear

    发明人： Michele L. R. Heffernan ,  Qun Kevin Fang ,  Robert J. Foglesong ,  Seth C. Hopkins ,  Cyprian O. Ogbu ,  Mustapha Soukri ,  Kerry L. Spear

    IPC分类号： A61K31/403 ,  C07D209/52 ,  C07D209/56

    CPC分类号： C07D209/42 ,  C07D209/52 ,  C07D209/94 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04

    摘要： The present invention provides novel inhibitors of the enzyme D-amino acid oxidase. The compounds of the invention are useful for treating or preventing diseases and/or condition, wherein modulation of D-serine levels, and/or its oxidative products, is effective in ameliorating symptoms. The invention further provides methods of enhancing learning, memory and/or cognition. For example, the invention provides methods for treating or preventing loss of memory and/or cognition associated with neurodegenerative diseases, such as Alzheimer's disease. The invention further provides methods for preventing loss of neuronal function characteristic of neurodegenerative diseases. In addition, methods are provided for the treatment or prevention of neuropsychiatric diseases (e.g., schizophrenia) and for the treatment or prevention of pain and ataxia.

    摘要翻译： 本发明提供D-氨基酸氧化酶酶的新型抑制剂。 本发明的化合物可用于治疗或预防疾病和/或病症，其中D-丝氨酸水平和/或其氧化产物的调节在改善症状中是有效的。 本发明还提供增强学习，记忆和/或认知的方法。 例如，本发明提供了治疗或预防与神经变性疾病如阿尔茨海默病有关的记忆丧失和/或认知丧失的方法。 本发明还提供了用于预防神经变性疾病的神经元功能特征丧失的方法。 此外，提供了用于治疗或预防神经精神疾病（例如精神分裂症）和用于治疗或预防疼痛和共济失调的方法。

    Fluoro-substituted inhibitors of D-amino acid oxidase
    7.
    发明授权
    Fluoro-substituted inhibitors of D-amino acid oxidase 有权
    氟取代的D-氨基酸氧化酶抑制剂

    公开(公告)号：US07884124B2

    公开(公告)日：2011-02-08

    申请号：US11772798

    申请日：2007-07-02

    申请人： Michele L. R. Heffernan ,  Robert J. Foglesong ,  Seth C. Hopkins ,  Mustapha Soukri ,  Steven W. Jones ,  Kerry L. Spear ,  Mark A. Varney

    发明人： Michele L. R. Heffernan ,  Robert J. Foglesong ,  Seth C. Hopkins ,  Mustapha Soukri ,  Steven W. Jones ,  Kerry L. Spear ,  Mark A. Varney

    IPC分类号： A61K31/40 ,  C07D487/02 ,  C07D491/02 ,  C07D495/02 ,  C07D497/02

    CPC分类号： C07D495/04 ,  C07D491/04

    摘要： This invention provides novel inhibitors of the enzyme D-amino acid oxidase as well as pharmaceutical compositions including the compounds of the invention. The invention also provides methods for the treatment and prevention of neurological disorders, such as neuropsychiatric and neurodegenerative diseases, as well as pain, ataxia and convulsion. The compounds of the invention have the general structure: wherein A is NH or S. Q is a member selected from CR1 and N. X and Y are members independently selected from O, S, CR2, N and NH. R1, R2 and R4 are members independently selected from H and F, provided that at least one member selected from R1, R2 and R4 is F. R6 is a member selected from O−X+ and OH, wherein X+ is a positive ion, which is a member selected from inorganic positive ions and organic positive ions.

    摘要翻译： 本发明提供了D-氨基酸氧化酶酶的新型抑制剂以及包含本发明化合物的药物组合物。 本发明还提供了治疗和预防神经系统疾病如神经精神和神经退行性疾病以及疼痛，共济失调和惊厥的方法。 本发明的化合物具有以下通式：其中A是NH或S.Q是选自CR1和N的成员.X和Y是独立地选自O，S，CR2，N和NH的成员。 R 1，R 2和R 4是独立地选自H和F的成员，条件是选自R 1，R 2和R 4中的至少一个是F.R 6是选自O-X +和OH的成员，其中X +是正离子，其中 是选自无机正离子和有机正离子的成员。

    FUSED HETEROCYCLES
    8.
    发明申请
    FUSED HETEROCYCLES 审中-公开
    熔融杂环

    公开(公告)号：US20100029741A1

    公开(公告)日：2010-02-04

    申请号：US12537896

    申请日：2009-08-07

    申请人： James M. Dorsey ,  Michele L. R. Heffernan ,  Qun Kevin Fang ,  Robert J. Foglesong ,  Seth C. Hopkins ,  Cyprian O. Ogbu ,  Mustapha Soukri ,  Kerry L. Spear

    发明人： James M. Dorsey ,  Michele L. R. Heffernan ,  Qun Kevin Fang ,  Robert J. Foglesong ,  Seth C. Hopkins ,  Cyprian O. Ogbu ,  Mustapha Soukri ,  Kerry L. Spear

    IPC分类号： A61K31/407 ,  A61P25/00

    CPC分类号： A61K31/407 ,  C07D491/04 ,  C07D495/04

    摘要： This invention provides methods of improving cognitive function by administering to a subject a therapeutically effective amount of a fused heterocycle having the formula: in which R1 is a member selected from the group consisting of H, substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl. R2 is a member selected from the group consisting of H substituted or unsubstituted alkenyl, substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl. R3 is a member selected from the group consisting of H, C1-C6 substituted or unsubstituted alkyl, substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl. R4 is a member selected from OH and O−X+, in which X+ is positive ion which is a member selected from organic positive ions and inorganic positive ions. Substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl moieties have the formula: in which Ar is a member selected from the group consisting of substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. The index n is an integer from 1 to 4.

    摘要翻译： 本发明提供了通过向受试者施用治疗有效量的具有下式的稠合杂环来提高认知功能的方法：其中R1是选自H，取代或未取代的芳基烷基和取代或未取代的杂芳基烷基的成员。 R2是选自H取代或未取代的烯基，取代或未取代的芳基烷基和取代或未取代的杂芳基烷基的成员。 R3是选自H，C1-C6取代或未取代的烷基，取代或未取代的芳基烷基和取代或未取代的杂芳基烷基的成员。 R4是选自OH和O-X +的成员，其中X +是选自有机正离子和无机阳离子的正离子。 取代或未取代的芳基烷基和取代或未取代的杂芳基烷基部分具有下式：其中Ar是选自取代或未取代的芳基和取代或未取代的杂芳基的成员。 索引n是从1到4的整数。