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    PYRROLE AND PYRAZOLE DAAO INHIBITORS
    1.
    发明申请
    PYRROLE AND PYRAZOLE DAAO INHIBITORS 审中-公开
    吡咯和吡唑多糖抑制剂

    公开(公告)号：US20110092559A1

    公开(公告)日：2011-04-21

    申请号：US12965175

    申请日：2010-12-10

    Applicant: Q. Kevin FANG ,  Seth HOPKINS ,  Michele HEFFERNAN ,  Milan CHYTIL

    Inventor： Q. Kevin FANG ,  Seth HOPKINS ,  Michele HEFFERNAN ,  Milan CHYTIL

    IPC: A61K31/415 ,  A61K31/416 ,  A61P21/00 ,  A61P25/28 ,  A61P25/18 ,  A61P25/04

    CPC classification number: C07D231/56 ,  C07D207/34 ,  C07D209/42 ,  C07D209/44 ,  C07D231/14 ,  C07D231/16 ,  C07D231/54 ,  C07D491/04

    Abstract: Methods for increasing D-Serine concentration and reducing concentration of the toxic products of D-Serine oxidation, for enhancing learning, memory and/or cognition, or for treating schizophrenia, Alzheimer's disease, ataxia or neuropathic pain, or preventing loss in neuronal function characteristic of neurodegenerative diseases involve administering to a subject in need of treatment a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof: wherein R1 and R2 are independently selected from hydrogen, halo, nitro, alkyl, acyl, alkylaryl, and XYR5; or R1 and R2, taken together, form a 5, 6, 7 or 8-membered substituted or unsubstituted carbocyclic or heterocyclic group; X and Y are independently selected from O, S, NH, and (CR6R7)n; R3 is hydrogen, alkyl or M+; M is aluminum, calcium, lithium, magnesium, potassium, sodium, zinc ion or a mixture thereof; Z is N or CR4; R4 is from selected from hydrogen, halo, nitro, alkyl, alkylaryl, and XYR5; R5 is selected from aryl, substituted aryl, heteroaryl and substituted heteroaryl; R6 and R7 are independently selected from hydrogen and alkyl; n is an integer from 1 to 6; at least one of R1, R2 and R4 is other than hydrogen; and at least one of X and Y is (CR6R7)n. D-serine or cycloserine may be coadministered along with the compound of formula I.

    Abstract translation: 提高D-丝氨酸浓度，降低D-丝氨酸氧化毒性浓度的方法，用于增强学习，记忆和/或认知，或用于治疗精神分裂症，阿尔茨海默病，共济失调或神经性疼痛，或防止神经功能特征丧失 的神经变性疾病涉及向需要治疗的受试者施用治疗有效量的式I化合物或其药学上可接受的盐或溶剂合物：其中R 1和R 2独立地选自氢，卤素，硝基，烷基，酰基， 烷基芳基和XYR5; 或R 1和R 2一起形成5,6,7或8元取代或未取代的碳环或杂环基团; X和Y独立地选自O，S，NH和（CR 6 R 7）n; R3是氢，烷基或M +; M是铝，钙，锂，镁，钾，钠，锌离子或它们的混合物; Z是N或CR4; R4选自氢，卤素，硝基，烷基，烷基芳基和XYR5; R 5选自芳基，取代的芳基，杂芳基和取代的杂芳基; R6和R7独立地选自氢和烷基; n是1至6的整数; R 1，R 2和R 4中的至少一个不是氢; 并且X和Y中的至少一个是（CR 6 R 7）n。 D-丝氨酸或环丝氨酸可以与式I化合物共同给药。

    Pyrrole and Pyrazole DAAO Inhibitors
    3.
    发明申请
    Pyrrole and Pyrazole DAAO Inhibitors 有权
    吡咯和吡唑DAAO抑制剂

    公开(公告)号：US20090170916A1

    公开(公告)日：2009-07-02

    申请号：US12335250

    申请日：2008-12-15

    Applicant: Q. Kevin Fang ,  Seth Hopkins ,  Michele Heffernan ,  Milan Chytil

    Inventor： Q. Kevin Fang ,  Seth Hopkins ,  Michele Heffernan ,  Milan Chytil

    IPC: A61K31/415 ,  A61K31/42 ,  A61P25/18

    CPC classification number: C07D231/56 ,  C07D207/34 ,  C07D209/42 ,  C07D209/44 ,  C07D231/14 ,  C07D231/16 ,  C07D231/54 ,  C07D491/04

    Abstract: Methods for increasing D-Serine concentration and reducing concentration of the toxic products of D-Serine oxidation, for enhancing learning, memory and/or cognition, or for treating schizophrenia, Alzheimer's disease, ataxia or neuropathic pain, or preventing loss in neuronal function characteristic of neurodegenerative diseases involve administering to a subject in need of treatment a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof: wherein R1 and R2 are independently selected from hydrogen, halo, nitro, alkyl, acyl, alkylaryl, and XYR5; or R1 and R2, taken together, form a 5, 6, 7 or 8-membered substituted or unsubstituted carbocyclic or heterocyclic group; X and Y are independently selected from O, S, NH, and (CR6R7)n; R3 is hydrogen, alkyl or M+; M is aluminum, calcium, lithium, magnesium, potassium, sodium, zinc ion or a mixture thereof; Z is N or CR4; R4 is from selected from hydrogen, halo, nitro, alkyl, alkylaryl, and XYR5; R5 is selected from aryl, substituted aryl, heteroaryl and substituted heteroaryl; R6 and R7 are independently selected from hydrogen and alkyl; n is an integer from 1 to 6; at least one of R1, R2 and R4 is other than hydrogen; and at least one of X and Y is (CR6R7)n. D-serine or cycloserine may be coadministered along with the compound of formula I.

    Abstract translation: 提高D-丝氨酸浓度，降低D-丝氨酸氧化毒性浓度的方法，用于增强学习，记忆和/或认知，或用于治疗精神分裂症，阿尔茨海默病，共济失调或神经性疼痛，或防止神经功能特征丧失 的神经变性疾病涉及向需要治疗的受试者施用治疗有效量的式I化合物或其药学上可接受的盐或溶剂合物：其中R 1和R 2独立地选自氢，卤素，硝基，烷基，酰基， 烷基芳基和XYR5; 或R 1和R 2一起形成5,6,7或8元取代或未取代的碳环或杂环基团; X和Y独立地选自O，S，NH和（CR 6 R 7）n; R3是氢，烷基或M +; M是铝，钙，锂，镁，钾，钠，锌离子或它们的混合物; Z是N或CR4; R4选自氢，卤素，硝基，烷基，烷基芳基和XYR5; R 5选自芳基，取代的芳基，杂芳基和取代的杂芳基; R6和R7独立地选自氢和烷基; n是1至6的整数; R 1，R 2和R 4中的至少一个不是氢; 并且X和Y中的至少一个是（CR 6 R 7）n。 D-丝氨酸或环丝氨酸可以与式I化合物共同给药。

    Pyrrole and pyrazole DAAO inhibitors
    5.
    发明授权
    Pyrrole and pyrazole DAAO inhibitors 有权

    公开(公告)号：US07488747B2

    公开(公告)日：2009-02-10

    申请号：US11023924

    申请日：2004-12-28

    Applicant: Q. Kevin Fang ,  Seth Hopkins ,  Michele Heffernan ,  Milan Chytil

    Inventor： Q. Kevin Fang ,  Seth Hopkins ,  Michele Heffernan ,  Milan Chytil

    IPC: A61K31/416 ,  A61K31/405 ,  C07D231/56

    CPC classification number: C07D231/56 ,  C07D207/34 ,  C07D209/42 ,  C07D209/44 ,  C07D231/14 ,  C07D231/16 ,  C07D231/54 ,  C07D491/04

    Abstract: Methods for increasing D-Serine concentration and reducing concentration of the toxic products of D-Serine oxidation, for enhancing learning, memory and/or cognition, or for treating schizophrenia, Alzheimer's disease, ataxia or neuropathic pain, or preventing loss in neuronal function characteristic of neurodegenerative diseases involve administering to a subject in need of treatment a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof: wherein R1 and R2 are independently selected from hydrogen, halo, nitro, alkyl, acyl, alkylaryl, and XYR5; or R1 and R2, taken together, form a 5, 6, 7 or 8-membered substituted or unsubstituted carbocyclic or heterocyclic group; X and Y are independently selected from O, S, NH, and (CR6R7)n; R3 is hydrogen, alkyl or M+; M is aluminum, calcium, lithium, magnesium, potassium, sodium, zinc ion or a mixture thereof; Z is N or CR4; R4 is from selected from hydrogen, halo, nitro, alkyl, alkylaryl, and XYR5; R5 is selected from aryl, substituted aryl, heteroaryl and substituted heteroaryl; R6 and R7 are independently selected from hydrogen and alkyl; n is an integer from 1 to 6; at least one of R1, R2 and R4 is other than hydrogen; and at least one of X and Y is (CR6R7)n. D-serine or cycloserine may be coadministered along with the compound of formula I.

    Pyrrole and pyrazole DAAO inhibitors
    7.
    发明授权
    Pyrrole and pyrazole DAAO inhibitors 有权
    吡咯和吡唑DAAO抑制剂

    公开(公告)号：US07615572B2

    公开(公告)日：2009-11-10

    申请号：US12335250

    申请日：2008-12-15

    Applicant: Q. Kevin Fang ,  Seth Hopkins ,  Michele Heffernan ,  Milan Chytil

    Inventor： Q. Kevin Fang ,  Seth Hopkins ,  Michele Heffernan ,  Milan Chytil

    IPC: A61K31/416

    CPC classification number: C07D231/56 ,  C07D207/34 ,  C07D209/42 ,  C07D209/44 ,  C07D231/14 ,  C07D231/16 ,  C07D231/54 ,  C07D491/04

    Abstract: Methods for increasing D-Serine concentration and reducing concentration of the toxic products of D-Serine oxidation, for enhancing learning, memory and/or cognition, or for treating schizophrenia, Alzheimer's disease, ataxia or neuropathic pain, or preventing loss in neuronal function characteristic of neurodegenerative diseases involve administering to a subject in need of treatment a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof: wherein R1 and R2 are independently selected from hydrogen, halo, nitro, alkyl, acyl, alkylaryl, and XYR5; or R1 and R2, taken together, form a 5, 6, 7 or 8-membered substituted or unsubstituted carbocyclic or heterocyclic group; X and Y are independently selected from O, S, NH, and (CR6R7)n; R3 is hydrogen, alkyl or M+; M is aluminum, calcium, lithium, magnesium, potassium, sodium, zinc ion or a mixture thereof; Z is N or CR4; R4 is from selected from hydrogen, halo, nitro, alkyl, alkylaryl, and XYR5; R5 is selected from aryl, substituted aryl, heteroaryl and substituted heteroaryl; R6 and R7 are independently selected from hydrogen and alkyl; n is an integer from 1 to 6; at least one of R1, R2 and R4 is other than hydrogen; and at least one of X and Y is (CR6R7)n. D-serine or cycloserine may be coadministered along with the compound of formula I.

    Abstract translation: 提高D-丝氨酸浓度，降低D-丝氨酸氧化毒性浓度的方法，用于增强学习，记忆和/或认知，或用于治疗精神分裂症，阿尔茨海默病，共济失调或神经性疼痛，或防止神经功能特征丧失 的神经变性疾病涉及向需要治疗的受试者施用治疗有效量的式I化合物或其药学上可接受的盐或溶剂合物：其中R 1和R 2独立地选自氢，卤素，硝基，烷基，酰基， 烷基芳基和XYR5; 或R 1和R 2一起形成5,6,7或8元取代或未取代的碳环或杂环基团; X和Y独立地选自O，S，NH和（CR 6 R 7）n; R3是氢，烷基或M +; M是铝，钙，锂，镁，钾，钠，锌离子或它们的混合物; Z是N或CR4; R4选自氢，卤素，硝基，烷基，烷基芳基和XYR5; R 5选自芳基，取代的芳基，杂芳基和取代的杂芳基; R6和R7独立地选自氢和烷基; n是1至6的整数; R 1，R 2和R 4中的至少一个不是氢; 并且X和Y中的至少一个是（CR 6 R 7）n。 D-丝氨酸或环丝氨酸可以与式I化合物共同给药。

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