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    High affinity ligands for nociceptin receptor ORL-1
    1.
    发明授权
    High affinity ligands for nociceptin receptor ORL-1 失效
    伤害感受器受体ORL-1的高亲和力配体

    公开(公告)号：US06716846B2

    公开(公告)日：2004-04-06

    申请号：US10155277

    申请日：2002-05-23

    申请人： Deen Tulshian ,  Ginny D. Ho ,  Lisa S. Silverman ,  Julius J. Matasi ,  Robbie L. McLeod ,  John A. Hey ,  Richard W. Chapman ,  Ana Bercovici ,  Francis M. Cuss

    发明人： Deen Tulshian ,  Ginny D. Ho ,  Lisa S. Silverman ,  Julius J. Matasi ,  Robbie L. McLeod ,  John A. Hey ,  Richard W. Chapman ,  Ana Bercovici ,  Francis M. Cuss

    IPC分类号： C07D40306

    CPC分类号： A61K45/06 ,  A61K31/00 ,  A61K31/438 ,  A61K31/439 ,  A61K31/451 ,  A61K31/4535 ,  A61K31/454

    摘要： Novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: the dotted line represents an optional double bond; X1 is optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl; X2 is —CHO, —CN, optionally substituted amino, alkyl, or aryl; or X1 is optionally substituted benzofused heterocyclyl and X2 is hydrogen; or X1 and X2 together form an optionally benzofused spiro heterocyclyl group R1, R2, R3 and R4 are independently H and alkyl, or (R1 and R4) or (R2 and R3) or (R1 and R3) or (R2 and R4) together can form an alkylene bridge of 1 to 3 carbon atoms; Z1 is optionally substituted alkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, or —CO2(alkyl or substituted amino) or CN; Z2 is H or Z1; Z3 is H oralkyl; or Z1, Z2 and Z3, together with the carbon to which they are attached, form bicyclic saturated or unsaturated rings; pharmaceutical compositions therefore, and the use of said compounds as nociceptin receptor inhibitors useful in the treatment of pain, anxiety, cough, asthma, depression and alcohol abuse are disclosed.

    摘要翻译： 式的新型化合物或其药学上可接受的盐或溶剂合物，其中：虚线表示任选的双键; X 1为任选取代的烷基，环烷基，芳基，杂芳基或杂环烷基; X 2为-CHO， - CN，任选取代的氨基，烷基或芳基;或X 1是任选取代的苯并稠合的杂环基，X 2是氢;或X 1和X 2一起形成任选的苯并稠合的螺杂环基R 1， R 2，R 3和R 4独立地为H和烷基，或（R 1和R 4）或（R 2和R 3）或（R 1） >和R 3）或（R 2和R 4）可以一起形成1至3个碳原子的亚烷基桥; Z 1是任选取代的烷基，芳基，杂芳基，环烷基或杂环烷基，或 -CO 2（烷基或取代的氨基）或CN; Z 2是H或Z 1; Z 3是H或烷基; 或Z 1，Z 2和Z 3与它们所连接的碳一起形成双环饱和或不饱和环; 因此，公开了用于治疗疼痛，焦虑，咳嗽，哮喘，抑郁和酒精滥用的所述化合物作为伤害感受肽受体抑制剂的用途。

    High affinity ligands for nociceptin receptor ORL-1
    2.
    发明授权
    High affinity ligands for nociceptin receptor ORL-1 有权
    伤害感受器受体ORL-1的高亲和力配体

    公开(公告)号：US07094784B2

    公开(公告)日：2006-08-22

    申请号：US10761977

    申请日：2004-01-21

    申请人： Deen Tulshian ,  Ginny D. Ho ,  Lisa S. Silverman ,  Julius J. Matasi ,  Robbie L. McLeod ,  John A. Hey ,  Richard W. Chapman ,  Ana Bercovici ,  Francis M. Cuss

    发明人： Deen Tulshian ,  Ginny D. Ho ,  Lisa S. Silverman ,  Julius J. Matasi ,  Robbie L. McLeod ,  John A. Hey ,  Richard W. Chapman ,  Ana Bercovici ,  Francis M. Cuss

    IPC分类号： C07D401/04 ,  A61K31/46

    CPC分类号： A61K45/06 ,  A61K31/00 ,  A61K31/438 ,  A61K31/439 ,  A61K31/451 ,  A61K31/4535 ,  A61K31/454

    摘要： Novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: the dotted line represents an optional double bond; X1 is optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl; X2 is —CHO, —CN, optionally substituted amino, alkyl, or aryl; or X1 is optionally substituted benzofused heterocyclyl and X2 is hydrogen; or X1 and X2 together form an optionally benzofused spiro heterocyclyl group R1, R2, R3 and R4 are independently H and alkyl, or (R1 and R4) or (R2 and R3) or (R1 and R3) or (R2 and R4) together can form an alkylene bridge of 1 to 3 carbon atoms; Z1 is optionally substituted alkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, or —CO2(alkyl or substituted amino) or CN ; Z2 is H or Z1; Z3 is H oralkyl; or Z1, Z2 and Z3, together with the carbon to which they are attached, form bicyclic saturated or unsaturated rings; pharmaceutical compositions therefore, and the use of said compounds as nociceptin receptor inhibitors useful in the treatment of pain, anxiety, cough, asthma, depression and alcohol abuse are disclosed.

    摘要翻译： 新型式的化合物或其药学上可接受的盐或溶剂合物，其中：虚线表示任选的双键; X 1是任选取代的烷基，环烷基，芳基，杂芳基或杂环烷基; X 2是-CHO，-CN，任选取代的氨基，烷基或芳基; 或X 1是任选取代的苯并稠合的杂环基，X 2是氢; 或X 1和X 2一起形成任选的苯并稠合的螺杂环基R 1，R 2，R 2， 或者R 4和R 4独立地是H和烷基，或者（R 1和R 4）和（R 0） 或者R 2和R 3）或（R 1和R 3）或（R 2） 和R 4）可以形成1至3个碳原子的亚烷基桥; Z 1是任选取代的烷基，芳基，杂芳基，环烷基或杂环烷基或-CO 2（烷基或取代的氨基）或CN; Z 2是H或Z 1; Z 3是H或烷基; 或Z 1，Z 2和Z 3与它们所连接的碳一起形成双环饱和或不饱和环; 因此，公开了用于治疗疼痛，焦虑，咳嗽，哮喘，抑郁和酒精滥用的所述化合物作为伤害感受肽受体抑制剂的用途。

    High affinity ligands for nociceptin receptor ORL-1
    3.
    发明授权
    High affinity ligands for nociceptin receptor ORL-1 有权
    伤害感受器受体ORL-1的高亲和力配体

    公开(公告)号：US06455527B2

    公开(公告)日：2002-09-24

    申请号：US09769824

    申请日：2001-01-25

    申请人： Deen Tulshian ,  Ginny D. Ho ,  Lisa S. Silverman ,  Julius J. Matasi ,  Robbie L. McLeod ,  John A. Hey ,  Richard W. Chapman ,  Ana Bercovici ,  Francis M. Cuss

    发明人： Deen Tulshian ,  Ginny D. Ho ,  Lisa S. Silverman ,  Julius J. Matasi ,  Robbie L. McLeod ,  John A. Hey ,  Richard W. Chapman ,  Ana Bercovici ,  Francis M. Cuss

    IPC分类号： A61K31445

    CPC分类号： A61K45/06 ,  A61K31/00 ,  A61K31/438 ,  A61K31/439 ,  A61K31/451 ,  A61K31/4535 ,  A61K31/454

    摘要： Novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: the dotted line represents an optional double bond; X1 is optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl; X2 is —CHO, —CN, optionally substituted amino, alkyl, or aryl; or X1 is optionally substituted benzofused heterocyclyl and X2 is hydrogen; or X1 and X2 together form an optionally benzofused spiro heterocyclyl group R1, R2, R3 and R4 are independently H and alkyl, or (R1 and R4) or (R2 and R3) or (R1 and R3) or (R2 and R4) together can form an alkylene bridge of 1 to 3 carbon atoms; Z1 is optionally substituted alkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, or —CO2(alkyl or substituted amino) or CN ; Z2 is H or Z1; Z3 is H oralkyl; or Z1, Z2 and Z3, together with the carbon to which they are attached, form bicyclic saturated or unsaturated rings; pharmaceutical compositions therefore, and the use of said compounds as nociceptin receptor inhibitors useful in the treatment of pain, anxiety, cough, asthma, depression and alcohol abuse are disclosed.

    摘要翻译： 式的新型化合物或其药学上可接受的盐或溶剂化物，其中：虚线表示任选的双键; X 1为任选取代的烷基，环烷基，芳基，杂芳基或杂环烷基; X 2为-CHO，-CN，任选取代的氨基， 烷基或芳基;或X 1是任选取代的苯并稠合的杂环基，并且X 2是氢;或者X 1和X 2一起形成任选的苯并稠合的螺杂环基R1，R2，R3和R4独立地是H和烷基，或（R1和R4）或 和（R 3和R 3）或（R 1和R 3）或（R 2和R 4）在一起可以形成1至3个碳原子的亚烷基桥; Z 1是任选取代的烷基，芳基，杂芳基，环烷基或杂环烷基，或-CO 2（烷基或取代的氨基 ）或CN; Z2是H或Z1; Z 3是H或烷基; 或Z 1，Z 2和Z 3与它们所连接的碳一起形成双环饱和或不饱和环;因此，药物组合物以及所述化合物用作疼痛，焦虑，咳嗽，哮喘的伤害感受肽受体抑制剂的用途 ，公开抑郁症和酗酒。

    High affinity ligands for nociceptin receptor ORL-1
    4.
    发明授权
    High affinity ligands for nociceptin receptor ORL-1 有权
    伤害感受器受体ORL-1的高亲和力配体

    公开(公告)号：US06262066B1

    公开(公告)日：2001-07-17

    申请号：US09359771

    申请日：1999-07-26

    申请人： Deen Tulshian ,  Ginny D. Ho ,  Lisa S. Silverman ,  Julius J. Matasi ,  Robbie L. McLeod ,  John A. Hey ,  Richard W. Chapman ,  Ana Bercovici ,  Francis M. Cuss

    发明人： Deen Tulshian ,  Ginny D. Ho ,  Lisa S. Silverman ,  Julius J. Matasi ,  Robbie L. McLeod ,  John A. Hey ,  Richard W. Chapman ,  Ana Bercovici ,  Francis M. Cuss

    IPC分类号： C07D22122

    CPC分类号： A61K45/06 ,  A61K31/00 ,  A61K31/438 ,  A61K31/439 ,  A61K31/451 ,  A61K31/4535 ,  A61K31/454

    摘要： Novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: the dotted line represents an optional double bond; X1 is optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl; X2 is —CHO, —CN, optionally substituted amino, alkyl, or aryl; or X1 is optionally substituted benzofused heterocyclyl and X2 is hydrogen; or X1 and X2 together form an optionally benzofused Spiro heterocyclyl group R1, R2, R3 and R4 are independently H and alkyl, or (R1 and R4) or (R2 and R3) or (R1 and R3) or (R2 and R4) together can form an alkylene bridge of 1 to 3 carbon atoms; Z1 is optionally substituted alkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, or —CO2(alkyl or substituted amino) or CN; Z2 is H or Z1; Z3 is H oralkyl; or Z1, Z2 and Z3, together with the carbon to which they are attached, form bicyclic saturated or unsaturated rings; pharmaceutical compositions therefore, and the use of said compounds as nociceptin receptor inhibitors useful in the treatment of pain, anxiety, cough, asthma, depression and alcohol abuse are disclosed.

    摘要翻译： 式的新型化合物或其药学上可接受的盐或溶剂化物，其中：虚线表示任选的双键; X 1为任选取代的烷基，环烷基，芳基，杂芳基或杂环烷基; X 2为-CHO，-CN，任选取代的氨基， 烷基或芳基;或X 1为任选取代的苯并稠合的杂环基，且X 2为氢;或X 1和X 2一起形成任选的苯并稠合的螺杂环基R1，R2，R3和R4独立地为H和烷基，或（R1和R4）或 和（R 3和R 3）或（R 1和R 3）或（R 2和R 4）在一起可以形成1至3个碳原子的亚烷基桥; Z 1是任选取代的烷基，芳基，杂芳基，环烷基或杂环烷基，或-CO 2（烷基或取代的氨基 ）或CN; Z2是H或Z1; Z 3是H或烷基; 或Z 1，Z 2和Z 3与它们所连接的碳一起形成双环饱和或不饱和环; 因此，公开了用于治疗疼痛，焦虑，咳嗽，哮喘，抑郁和酒精滥用的所述化合物作为伤害感受肽受体抑制剂的用途。