公开(公告)号：WO2006110638A3

公开(公告)日：2007-04-19

申请号：PCT/US2006013280

申请日：2006-04-10

申请人： MERCK & CO INC ,  CHEN CHIXU ,  EASTMAN BRIAN W ,  HU ESSA H

发明人： CHEN CHIXU ,  EASTMAN BRIAN W ,  HU ESSA H

IPC分类号： A61K31/498 ,  C07D241/36

CPC分类号： C07D471/04 ,  C07D519/00

摘要： The instant invention provides for compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.

摘要翻译： 本发明提供抑制Akt活性的化合物。 特别地，所公开的化合物选择性地抑制一种或两种Akt同种型。 本发明还提供了包含这种抑制化合物的组合物和通过将该化合物给予需要治疗癌症的患者来抑制Akt活性的方法。

公开(公告)号：WO2003051833A3

公开(公告)日：2003-06-26

申请号：PCT/US2002/040147

申请日：2002-12-13

申请人： MERCK & CO., INC. ,  COSFORD, Nicholas, D., P. ,  CHEN, Chixu ,  EASTMAN, Brian, W. ,  HUANG, Dehua ,  MUNOZ, Benito ,  PRASIT, Petpiboon ,  SMITH, Nicholas, D.

发明人： COSFORD, Nicholas, D., P. ,  CHEN, Chixu ,  EASTMAN, Brian, W. ,  HUANG, Dehua ,  MUNOZ, Benito ,  PRASIT, Petpiboon ,  SMITH, Nicholas, D.

IPC分类号： A61K31/437

摘要： Pyrazole compounds substituted directly, or by a bridge, with a heteroaryl moiety containing N adjacent to the point of connection of the heteroaryl, are mGluR5 modulators useful in the treatment of psychiatric and mood disorders such as, for example, schizophrenia, anxiety, depression, bipolar disorder and panic, as well as in the treatment of pain, circadian rhythm disorders, and other diseases.

公开(公告)号：WO2007050050A2

公开(公告)日：2007-05-03

申请号：PCT/US2005/035921

申请日：2005-10-06

申请人： MERCK & CO., INC. ,  COSFORD, Nicholas, D. ,  SEIDERS, Thomas, J. ,  PAYNE, Joseph ,  ROPPE, Jeffrey, R. ,  HUANG, Dehua ,  SMITH, Nicholas, D. ,  POON, Steve, F. ,  KING, Chris ,  EASTMAN, Brian, W. ,  WANG, Bowei ,  ARRUDA, Jeannie, M. ,  VERNIER, Jean-Michel ,  ZHAO, Xiumin

发明人： COSFORD, Nicholas, D. ,  SEIDERS, Thomas, J. ,  PAYNE, Joseph ,  ROPPE, Jeffrey, R. ,  HUANG, Dehua ,  SMITH, Nicholas, D. ,  POON, Steve, F. ,  KING, Chris ,  EASTMAN, Brian, W. ,  WANG, Bowei ,  ARRUDA, Jeannie, M. ,  VERNIER, Jean-Michel ,  ZHAO, Xiumin

CPC分类号： C07D417/06 ,  C07D417/14 ,  C07D471/04

摘要： The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

摘要翻译： 由于在效力和/或药代动力学和/或选择性和/或体内受体占有性方面具有有利的性质，鉴定了具有药物性质特征的独特系列化合物。 具体地，选择由亚乙炔连接到吡啶环的3位或嘧啶环的5位的1,3-噻唑-2-基环成员，其中环被选定的取代基取代，得到 具有优异药物性质的化合物。 本发明包括这些杂环化合物的药学上可接受的盐形式，特别是氯化物盐和三氟乙酸盐。

公开(公告)号：WO2005100356A1

公开(公告)日：2005-10-27

申请号：PCT/US2005/011561

申请日：2005-04-05

申请人： MERCK & CO., INC. ,  BILODEAU, Mark, T. ,  CHEN, Chixu ,  COSFORD, Nicholas, D., P. ,  EASTMAN, Brian, W. ,  HARTNETT, John, C. ,  HU, Essa, H. ,  MANLEY, Peter, J. ,  NEILSON, Lou, Anne ,  TEHRANI, Lida, R. ,  WU, Zhicai

发明人： BILODEAU, Mark, T. ,  CHEN, Chixu ,  COSFORD, Nicholas, D., P. ,  EASTMAN, Brian, W. ,  HARTNETT, John, C. ,  HU, Essa, H. ,  MANLEY, Peter, J. ,  NEILSON, Lou, Anne ,  TEHRANI, Lida, R. ,  WU, Zhicai

IPC分类号： C07D471/04

CPC分类号： C07D471/04 ,  C07D519/00

摘要： The present invention is directed to compounds which contain substituted napthyridines which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention.

摘要翻译： 本发明涉及含有抑制Akt（丝氨酸/苏氨酸蛋白激酶）活性的取代萘啶的化合物。 本发明还涉及含有本发明化合物的治疗组合物和治疗癌症的方法，包括施用本发明化合物。

公开(公告)号：WO2004089303A3

公开(公告)日：2005-04-28

申请号：PCT/US2004011651

申请日：2004-03-30

申请人： MERCK & CO INC ,  COSFORD NICHOLAS D P ,  EASTMAN BRIAN W ,  HUANG DEHUA ,  SMITH NICHOLAS D ,  TEHRANI LIDA R ,  ESSA HU

发明人： COSFORD NICHOLAS D P ,  EASTMAN BRIAN W ,  HUANG DEHUA ,  SMITH NICHOLAS D ,  TEHRANI LIDA R ,  ESSA HU

IPC分类号： A61K20060101 ,  C07D401/04

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D417/14 ,  C07D471/04

摘要： Novel pyrazole compounds such as compounds of the formula (I): (where A, A , A , B, R , W, X, Y and Z are as defined herein) in which the pyrazole is substituted directly, or by a bridge, with i) a heteroaryl moiety containing N adjacent to the point of connection of the heteroaryl, and ii) another heteroaryl or aryl ring, with at least one of the rings being further substituted with another ring, are mGluR5 modulators useful in the treatment of psychiatric and mood disorders such as, for example, schizophrenia, anxiety, depression, panic, and bipolar disorder, as well as in the treatment of pain, Parkinson's disease, cognitive dysfunction, epilepsy, circadian rhythm disorders, obesity, drug addiction, drug abuse, drug withdrawal and other diseases.

摘要翻译： 新颖的吡唑化合物如式（I）化合物：其中A，A 1，A 2，B，R 11，W，X，Y和Z如本文所定义），其中吡唑 直接或通过桥取代，其中i）杂芳基部分，其含有与杂芳基的连接点相邻的N，和ii）另外的杂芳基或芳基环，其中至少一个环进一步被另一个环取代， 是用于治疗精神病和情绪障碍（例如精神分裂症，焦虑，抑郁，恐慌和双相情感障碍）以及治疗疼痛，帕金森病，认知功能障碍，癫痫，昼夜节律紊乱的mGluR5调节剂 ，肥胖，吸毒成瘾，药物滥用，戒毒等疾病。

公开(公告)号：WO2007050050A3

公开(公告)日：2008-02-07

申请号：PCT/US2005035921

申请日：2005-10-06

申请人： MERCK & CO INC ,  COSFORD NICHOLAS D ,  SEIDERS THOMAS J ,  PAYNE JOSEPH ,  ROPPE JEFFREY R ,  HUANG DEHUA ,  SMITH NICHOLAS D ,  POON STEVE F ,  KING CHRIS ,  EASTMAN BRIAN W ,  WANG BOWEI ,  ARRUDA JEANNIE M ,  VERNIER JEAN-MICHEL ,  ZHAO XIUMIN

发明人： COSFORD NICHOLAS D ,  SEIDERS THOMAS J ,  PAYNE JOSEPH ,  ROPPE JEFFREY R ,  HUANG DEHUA ,  SMITH NICHOLAS D ,  POON STEVE F ,  KING CHRIS ,  EASTMAN BRIAN W ,  WANG BOWEI ,  ARRUDA JEANNIE M ,  VERNIER JEAN-MICHEL ,  ZHAO XIUMIN

IPC分类号： C07D417/06 ,  C07D417/14 ,  C07D471/04

CPC分类号： C07D417/06 ,  C07D417/14 ,  C07D471/04

摘要： The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

摘要翻译： 由于它们在效力和/或药代动力学和/或选择性和/或体内受体占有性方面具有有利的性质，鉴定了具有药物性质特征的独特系列化合物。 具体地说，通过亚乙炔基连接到吡啶环的3位或嘧啶环的5位上的1,3-噻唑-2-基环成员的选择，其中环被选定的取代基取代，得到 具有优异药物性质的化合物。 本发明包括这些杂环化合物的药学上可接受的盐形式，特别是氯化物盐和三氟乙酸盐。

公开(公告)号：WO2006110638A2

公开(公告)日：2006-10-19

申请号：PCT/US2006/013280

申请日：2006-04-10

申请人： MERCK & CO., INC. ,  CHEN, Chixu ,  EASTMAN, Brian, W. ,  HU, Essa, H.

发明人： CHEN, Chixu ,  EASTMAN, Brian, W. ,  HU, Essa, H.

IPC分类号： A61K31/4439

CPC分类号： C07D471/04 ,  C07D519/00

摘要： The instant invention provides for compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.

摘要翻译： 本发明提供了抑制Akt活性的化合物。 特别地，所公开的化合物选择性地抑制一种或两种Akt同种型。 本发明还提供了包含这种抑制性化合物的组合物和通过将该化合物给予需要治疗癌症的患者来抑制Akt活性的方法。

公开(公告)号：WO2004089303A2

公开(公告)日：2004-10-21

申请号：PCT/US2004/011651

申请日：2004-03-30

申请人： MERCK & CO., INC. ,  COSFORD, Nicholas, D., P. ,  EASTMAN, Brian, W. ,  HUANG, Dehua ,  SMITH, Nicholas, D. ,  TEHRANI, Lida, R.

发明人： COSFORD, Nicholas, D., P. ,  EASTMAN, Brian, W. ,  HUANG, Dehua ,  SMITH, Nicholas, D. ,  TEHRANI, Lida, R.

IPC分类号： A61K

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D417/14 ,  C07D471/04

摘要： Novel pyrazole compounds such as compounds of the formula (I): (where A, A 1 , A 2 , B, R 11 , W, X, Y and Z are as defined herein) in which the pyrazole is substituted directly, or by a bridge, with i) a heteroaryl moiety containing N adjacent to the point of connection of the heteroaryl, and ii) another heteroaryl or aryl ring, with at least one of the rings being further substituted with another ring, are mGluR5 modulators useful in the treatment of psychiatric and mood disorders such as, for example, schizophrenia, anxiety, depression, panic, and bipolar disorder, as well as in the treatment of pain, Parkinson’s disease, cognitive dysfunction, epilepsy, circadian rhythm disorders, obesity, drug addiction, drug abuse, drug withdrawal and other diseases.

摘要翻译： 新颖的吡唑化合物如式（I）化合物：其中A，A 1，A 2，B，R 11，W，X，Y和Z如本文所定义），其中吡唑 直接或通过桥取代，其中i）杂芳基部分，其含有与杂芳基的连接点相邻的N，和ii）另外的杂芳基或芳基环，其中至少一个环进一步被另一个环取代， 是用于治疗精神病和情绪障碍（例如精神分裂症，焦虑，抑郁，恐慌和双相情感障碍）以及治疗疼痛，帕金森病，认知功能障碍，癫痫，昼夜节律紊乱的mGluR5调节剂 ，肥胖，吸毒成瘾，药物滥用，戒毒等疾病。

公开(公告)号：WO2003051833A2

公开(公告)日：2003-06-26

申请号：PCT/US2002/040147

申请日：2002-12-13

申请人： MERCK & CO., INC. ,  COSFORD, Nicholas, D., P. ,  CHEN, Chixu ,  EASTMAN, Brian, W. ,  HUANG, Dehua ,  MUNOZ, Benito ,  PRASIT, Petpiboon ,  SMITH, Nicholas, D.

发明人： COSFORD, Nicholas, D., P. ,  CHEN, Chixu ,  EASTMAN, Brian, W. ,  HUANG, Dehua ,  MUNOZ, Benito ,  PRASIT, Petpiboon ,  SMITH, Nicholas, D.

IPC分类号： C07D

CPC分类号： C07D231/38 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04

摘要： Pyrazole compounds substituted directly, or by a bridge, with a heteroaryl moiety containing N adjacent to the point of connection of the heteroaryl, are mGluR5 modulators useful in the treatment of psychiatric and mood disorders such as, for example, schizophrenia, anxiety, depression, bipolar disorder and panic, as well as in the treatment of pain, circadian rhythm disorders, and other diseases.

摘要翻译： 用邻近杂芳基连接点的含有N的杂芳基部分直接或通过桥来取代的吡唑化合物为用于治疗精神病和情绪障碍的mGluR5调节剂，例如用于 例如精神分裂症，焦虑症，抑郁症，双相情感障碍和恐慌症，以及用于治疗疼痛，昼夜节律紊乱和其他疾病。

公开(公告)号：WO2003077918A1

公开(公告)日：2003-09-25

申请号：PCT/US2003/007074

申请日：2003-03-07

申请人： MERCK & CO., INC. ,  SMITH, Nicholas, D. ,  COSFORD, Nicholas, D. P. ,  REGER, Thomas, R. ,  ROPPE, Jeffrey, R. ,  POON, Steven, F. ,  HUANG, Dehua ,  CHEN, Chixu ,  EASTMAN, Brian, W.

发明人： SMITH, Nicholas, D. ,  COSFORD, Nicholas, D. P. ,  REGER, Thomas, R. ,  ROPPE, Jeffrey, R. ,  POON, Steven, F. ,  HUANG, Dehua ,  CHEN, Chixu ,  EASTMAN, Brian, W.

IPC分类号： A61K31/4439

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04

摘要： Tetrazole compounds substituted directly, or by a bridge, with i) a heteroaryl moiety containing N adjacent to the point of connection of the heteroaryl and ii) another heteroaryl or aryl ring, with at least one of the rings being further substituted with another ring, are mGluR5 modulators useful in the treatment of psychiatric and mood disorders such as, for example, schizophrenia, anxiety, depression, panic, and bipolar disorder, as well as in the treatment of pain, Parkinson s disease, cognitive dysfunction, epilepsy, circadian rhythm disorders, drug addiction, drug abuse, drug withdrawal, obesity and other diseases.

摘要翻译： 直接或桥接的四唑化合物与i）杂芳基部分，该杂芳基部分含有邻近杂芳基的连接点的N，和ii）另一个杂芳基或芳基环，其中至少一个环进一步被另一个环取代， 是用于治疗精神病和情绪障碍（例如精神分裂症，焦虑，抑郁，恐慌和双相情感障碍）以及治疗疼痛，帕金森病，认知功能障碍，癫痫，昼夜节律的mGluR5调节剂 疾病，药物成瘾，药物滥用，戒毒，肥胖等疾病。