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。

公开(公告)号：US07166725B2

公开(公告)日：2007-01-23

申请号：US11024151

申请日：2004-12-28

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

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

IPC: C07D261/20 ,  A61K31/42

CPC classification number: C07D261/20

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 therapeutic amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof: wherein Z1 is N or CR3; Z2 is N or CR4; Z3is O or S; A is hydrogen, alkyl or M+; M is aluminum, calcium, lithium, magnesium, potassium, sodium, zinc or a mixture thereof; R1, R2, R3 and R4 are independently selected from hydrogen, alkyl, hydroxy alkoxy, aryl, acyl, halo, cyano, haloalkyl, NHCOOR5 and SO2NH2; R5 is aryl, arylalkyl, heteroaryl or heteroarylalkyl; at least one of R1, R2, R3 and R4 is other than hydrogen; and at least one of Z1 and Z2 is other than N.

Abstract translation: 提高D-丝氨酸浓度和降低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，或防止神经功能丧失的方法 神经变性疾病的特征包括向需要治疗的受试者施用治疗量的式I化合物或其药学上可接受的盐或溶剂合物：其中Z 1是N或CR 3 ; Z 2是N或CR 4; Z 3是O或S; A是氢，烷基或M + M是铝，钙，锂，镁，钾，钠，锌或它们的混合物; R 1，R 2，R 3和R 4独立地选自氢，烷基，羟基烷氧基， 芳基，酰基，卤素，氰基，卤代烷基，NHCOOR 5和SO 2 NH 2。 R 5是芳基，芳基烷基，杂芳基或杂芳基烷基; R 1，R 2，R 3和R 4中的至少一个不是氢; 并且Z 1和Z 2中的至少一个不是N。

公开(公告)号：US07893098B2

公开(公告)日：2011-02-22

申请号：US12566990

申请日：2009-09-25

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

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

IPC: A61K31/415 ,  C07D231/14 ,  C07D231/54

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。

公开(公告)号：US20100016397A1

公开(公告)日：2010-01-21

申请号：US12566990

申请日：2009-09-25

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

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

IPC: A61K31/415 ,  C07D231/54 ,  C07D231/14 ,  A61K31/416 ,  A61P25/00 ,  A61P25/18 ,  A61P25/28

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。

公开(公告)号：US20080058395A1

公开(公告)日：2008-03-06

申请号：US11825093

申请日：2007-07-02

Applicant: Michele Heffernan ,  James Dorsey ,  Qun Fang ,  Robert Foglesong ,  Seth Hopkins ,  Michael Jones ,  Steven Jones ,  Cyprian Ogbu ,  Joe Perales ,  Mustapha Soukri ,  Kerry Spear ,  Mark Varney

Inventor： Michele Heffernan ,  James Dorsey ,  Qun Fang ,  Robert Foglesong ,  Seth Hopkins ,  Michael Jones ,  Steven Jones ,  Cyprian Ogbu ,  Joe Perales ,  Mustapha Soukri ,  Kerry Spear ,  Mark Varney

IPC: A61K31/40 ,  A61K31/415 ,  A61K31/425 ,  A61K31/48 ,  A61P43/00 ,  C07D231/02 ,  C07D303/02 ,  C07D487/02 ,  C07D513/00

CPC classification number: C07D487/04 ,  C07D491/04 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04

Abstract: This invention provides novel inhibitors of the enzyme D-amino acid oxidase as well as pharmaceutical compositions including the compounds of the invention. Also provided are 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 Q is a member selected from O, S, CR1 and N, X and Y are members independently selected from CR2, O, S, N and NR3.

Abstract translation: 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。 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结构：其中Q是选自O，S，CR 1和N中的一个，X和Y是独立地选自CR 2， ，O，S，N和NR 3。

公开(公告)号：US20050143434A1

公开(公告)日：2005-06-30

申请号：US11024151

申请日：2004-12-28

Applicant: Q. Fang ,  Seth Hopkins ,  Steven Jones

Inventor： Q. Fang ,  Seth Hopkins ,  Steven Jones

IPC: A61K31/42 ,  C07D261/20

CPC classification number: C07D261/20

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 therapeutic amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof: wherein Z1 is N or CR3; Z2 is N or CR4; Z3is O or S; A is hydrogen, alkyl or M+; M is aluminum, calcium, lithium, magnesium, potassium, sodium, zinc or a mixture thereof; R1, R2, R3 and R4 are independently selected from hydrogen, alkyl, hydroxy alkoxy, aryl, acyl, halo, cyano, haloalkyl, NHCOOR5 and SO2NH2; R5 is aryl, arylalkyl, heteroaryl or heteroarylalkyl; at least one of R1, R2, R3 and R4 is other than hydrogen; and at least one of Z1 and Z2 is other than N.

Abstract translation: 提高D-丝氨酸浓度和降低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，或防止神经功能丧失的方法 神经变性疾病的特征包括向需要治疗的受试者施用治疗量的式I化合物或其药学上可接受的盐或溶剂合物：其中Z 1是N或CR 3 ; Z 2是N或CR 4; Z 3是O或S; A是氢，烷基或M + M是铝，钙，锂，镁，钾，钠，锌或它们的混合物; R 1，R 2，R 3和R 4独立地选自氢，烷基，羟基烷氧基， 芳基，酰基，卤素，氰基，卤代烷基，NHCOOR 5和SO 2 NH 2。 R 5是芳基，芳基烷基，杂芳基或杂芳基烷基; R 1，R 2，R 3和R 4中的至少一个不是氢; 并且Z 1和Z 2中的至少一个不是N。

公开(公告)号：US20080004327A1

公开(公告)日：2008-01-03

申请号：US11772798

申请日：2007-07-02

Applicant: Michele Heffernan ,  Robert Foglesong ,  Seth Hopkins ,  Mustapha Soukri ,  Steven Jones ,  Kerry Spear ,  Mark Varney

Inventor： Michele Heffernan ,  Robert Foglesong ,  Seth Hopkins ,  Mustapha Soukri ,  Steven Jones ,  Kerry Spear ,  Mark Varney

IPC: A61K31/407 ,  C07D491/02

CPC classification number: C07D495/04 ,  C07D491/04

Abstract: 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.

Abstract translation: 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一般结构：其中A是NH或S.Q是选自CR 1和N的成员.X和Y是独立地选自O，S，CR < > 2，N和NH。 R 1，R 2和R 4都是独立地选自H和F的成员，条件是选自R 1，R 2， R 1，R 2，R 4和R 4是F.R 6是选自O - >其中X + +为​​正离子，其为选自无机正离子和有机正离子的成员。

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.

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。

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。