公开(公告)号：US20110046127A1

公开(公告)日：2011-02-24

申请号：US12741765

申请日：2008-11-10

申请人： Paolo Pevarello ,  Ana Maria Garcia Collazo ,  Antonio Rodriguez Hergueta ,  Carl-Gustaf Pierre Saluste ,  Francisco Javier Ramos Lima ,  Esther Gonzalez Cantalapiedra ,  Julen Oyarzabal Santamarina

发明人： Paolo Pevarello ,  Ana Maria Garcia Collazo ,  Antonio Rodriguez Hergueta ,  Carl-Gustaf Pierre Saluste ,  Francisco Javier Ramos Lima ,  Esther Gonzalez Cantalapiedra ,  Julen Oyarzabal Santamarina

IPC分类号： A61K31/5377 ,  C07D487/04 ,  A61K31/5025 ,  C07D413/14 ,  A61P35/00

CPC分类号： C07D487/04

摘要： There is provided compounds of formula (I): wherein Z, M, R1, X, R3, R4 and R5 have meanings given in the description, an pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein kinase (e.g. a PIM family kinase or PI3-K) is desired and/or required, an particularly in the treatment of cancer.

摘要翻译： 提供式（I）化合物：其中Z，M，R 1，X，R 3，R 4和R 5具有在本说明书中给出的含义，其药学上可接受的酯，酰胺，溶剂化物或其盐，该化合物可用于 治疗其中期望和/或需要蛋白激酶（例如PIM家族激酶或PI3-K）的抑制的疾病，特别是治疗癌症。

公开(公告)号：US20130065883A1

公开(公告)日：2013-03-14

申请号：US13579781

申请日：2011-02-18

申请人： Joaquin Pastor Fernández ,  Julen Oyarzabal Santamarina ,  Carl-Gustaf Pierre Saluste ,  Carmen Blanco Aparicio ,  Rosa Maria Alvarez Escobar ,  Virginia Rivero Buceta

发明人： Joaquin Pastor Fernández ,  Julen Oyarzabal Santamarina ,  Carl-Gustaf Pierre Saluste ,  Carmen Blanco Aparicio ,  Rosa Maria Alvarez Escobar ,  Virginia Rivero Buceta

IPC分类号： C07D471/04 ,  A61K31/437 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/5377 ,  A61K31/537 ,  C07D471/10 ,  A61K31/438 ,  C07D498/10 ,  A61K31/5386 ,  A61P35/00 ,  A61P9/00 ,  A61P31/12 ,  A61P29/00 ,  A61P3/00 ,  A61P5/00 ,  A61P25/00 ,  A61P11/00 ,  A61P27/14 ,  A61P37/02 ,  A61K31/55

CPC分类号： A61K45/06 ,  A61K31/4192 ,  A61K31/437 ,  C07D471/04 ,  A61K2300/00

摘要： There is provided compounds of formula (I), wherein R1, R2, R3 and R4 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PIM family kinase, such as PIM-1, PIM-2 and/or PIM-3, and/or Flt3) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

摘要翻译： 提供式（I）化合物，其中R 1，R 2，R 3和R 4具有本说明书中给出的含义及其药学上可接受的酯，酰胺，溶剂化物或其盐，该化合物可用于治疗其中抑制 蛋白质或脂质激酶（例如PIM家族激酶，例如PIM-1，PIM-2和/或PIM-3和/或Flt3）是期望和/或需要的，特别是在治疗癌症或 增殖性疾病

公开(公告)号：US20100105694A1

公开(公告)日：2010-04-29

申请号：US12445243

申请日：2007-10-10

申请人： José Ignacio Andrés-Gil ,  Manuel Jesús Alcázar-Vaca ,  Maria Lourdes Linares De La Morena ,  Sonia Martinez Gonzalez ,  Julen Oyarzabal Santamarina ,  Joaquin Pastor-Fernández ,  Juan Antonio Vega-Ramiro ,  Francisca Delgado-Jiménez ,  Wilhelmus Helena Ignatius Maria Drinkenburg

发明人： José Ignacio Andrés-Gil ,  Manuel Jesús Alcázar-Vaca ,  Maria Lourdes Linares De La Morena ,  Sonia Martinez Gonzalez ,  Julen Oyarzabal Santamarina ,  Joaquin Pastor-Fernández ,  Juan Antonio Vega-Ramiro ,  Francisca Delgado-Jiménez ,  Wilhelmus Helena Ignatius Maria Drinkenburg

IPC分类号： A61K31/497 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D403/04 ,  C07D403/14 ,  C07D413/14 ,  A61P25/00 ,  A61P25/28

CPC分类号： C07D401/12 ,  C07D241/20

摘要： The present invention concerns substituted pyrazinone derivatives according to the general Formula (I) a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, an N-oxide form thereof or a quaternary ammonium salt thereof, wherein the variables are defined in claim 1, having selective 2C-adrenoceptor antagonist activity. It further relates to their preparation, compositions comprising them and their use as a medicine. The compounds according to the invention are useful for the prevention and/or treatment of central nervous system disorders, mood disorders, anxiety disorders, stress-related disorders associated with depression and/or anxiety, cognitive disorders, personality disorders, schizoaffective disorders, Parkinson's disease, dementia of the Alzheimer's type, chronic pain conditions, neurodegenerative diseases, addiction disorders, mood disorders and sexual dysfunction.

摘要翻译： 本发明涉及根据通式（I）的取代的吡嗪酮衍生物，其药学上可接受的酸或碱加成盐，其立体化学异构形式，其N-氧化物形式或其季铵盐，其中变量定义于 权利要求1，具有选择性的2C-肾上腺素受体拮抗剂活性。 它还涉及它们的制备，包含它们的组合物及其作为药物的用途。 根据本发明的化合物可用于预防和/或治疗中枢神经系统疾病，情绪障碍，焦虑障碍，与抑郁和/或焦虑相关的压力相关疾病，认知障碍，人格障碍，分裂情感障碍，帕金森病 ，阿尔茨海默病的痴呆，慢性疼痛病症，神经变性疾病，成瘾症，情绪障碍和性功能障碍。

公开(公告)号：US20140154232A1

公开(公告)日：2014-06-05

申请号：US13880893

申请日：2011-06-01

申请人： Manuel Serrano Marugan ,  Joaquin Pastor Fernández ,  Sonia Martínez González ,  Ana Ortega Molina ,  James R. Bischoff ,  Julen Oyarzabal Santamarina

发明人： Manuel Serrano Marugan ,  Joaquin Pastor Fernández ,  Sonia Martínez González ,  Ana Ortega Molina ,  James R. Bischoff ,  Julen Oyarzabal Santamarina

IPC分类号： A61K31/5377 ,  C07D471/10 ,  A61K45/06 ,  C07D487/04

CPC分类号： A61K45/06 ,  A61K31/35 ,  A61K31/4985 ,  A61K31/5377 ,  C07D471/10 ,  C07D487/04

摘要： The first aspect of the invention relates to a phosphoinositide 3-kinase inhibitor for use in the treatment or prevention of a disease or condition associated with the expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (Pgd1α) and/or uncoupling protein 1 (Thermogenin/Ucp1) in brown adipocytes. The disease or condition may be positive energy imbalance-associated, for example, obesity, an obesity-associated disease or condition, steatosis and biological aging (performance aging). Another aspect of the invention provides the use of a phosphoinositide 3-kinase inhibitor for promoting weight loss in an individual.

摘要翻译： 本发明的第一方面涉及用于治疗或预防与过氧化物酶体增殖物激活受体γ共激活因子1-α（Pgd1α）和/或解偶联蛋白1的表达相关的疾病或病症的磷酸肌醇3-激酶抑制剂 （Thermogenin / Ucp1）在棕色脂肪细胞。 疾病或病症可能是正能量失衡相关的，例如肥胖，肥胖相关疾病或病症，脂肪变性和生物衰老（性能衰老）。 本发明的另一方面提供了磷酸肌醇3-激酶抑制剂在个体中促进体重减轻的用途。

公开(公告)号：US08329704B2

公开(公告)日：2012-12-11

申请号：US12091365

申请日：2006-12-18

申请人： José Ignacio Andrés-Gil ,  Manuel Jesús Alcázar-Vaca ,  Rosa María Álvarez-Escobar ,  Julen Oyarzabal Santamarina ,  Frank Matthias Dautzenberg ,  Jacqueline Macritchie ,  Donald Simpson ,  Sonia Martinez Gonzalez

发明人： José Ignacio Andrés-Gil ,  Manuel Jesús Alcázar-Vaca ,  Rosa María Álvarez-Escobar ,  Julen Oyarzabal Santamarina ,  Frank Matthias Dautzenberg ,  Jacqueline Macritchie ,  Donald Simpson ,  Sonia Martinez Gonzalez

IPC分类号： A61K31/4965 ,  C07D241/02

CPC分类号： C07D241/20 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D491/10

摘要： The present invention concerns aryl and heteroaryl substituted pyrazinone derivatives having antagonistic melanin-concentrating hormone (MCH) activity, in particular MCH-1 activity according to the general Formula (I) a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, an N-oxide form thereof or a quaternary ammonium salt thereof, wherein the variables are defined in Claim 1. It further relates to their preparation, compositions comprising them and their use as a medicine. The compounds according to the invention are useful for the prevention and/or treatment of psychiatric disorders, including but not limited to anxiety, eating disorders, mood disorders, such as bipolar disorders and depression, psychoses, such as schizophrenia, and sleeping disorders; obesity; diabetes; sexual disorders and neurological disorders.

摘要翻译： 本发明涉及具有拮抗性黑色素浓缩激素（MCH）活性的芳基和杂芳基取代的吡嗪酮衍生物，特别是根据通式（I）的MCH-1活性，其药学上可接受的酸或碱加成盐，其立体化学异构形式 ，其N-氧化物形式或其季铵盐，其中所述变量在权利要求1中定义。它还涉及它们的制备，包含它们的组合物及其作为药物的用途。 根据本发明的化合物可用于预防和/或治疗精神病学障碍，包括但不限于焦虑，进食障碍，情绪障碍，例如双相性精神障碍和抑郁症，精神病如精神分裂症和睡眠障碍; 肥胖; 糖尿病; 性障碍和神经障碍。

公开(公告)号：US20090012062A1

公开(公告)日：2009-01-08

申请号：US12091365

申请日：2006-12-18

申请人： Jose Ignacio Andres-Gil ,  Manuel Jesus Alcazar-Vaca ,  Rosa Maria Alvarez-Escobar ,  Julen Oyarzabal Santamarina ,  Frank Matthias Dautzenberg ,  Jacqueline Macritchie ,  Donald Simpson ,  Sonia Martinez Gonzalez

发明人： Jose Ignacio Andres-Gil ,  Manuel Jesus Alcazar-Vaca ,  Rosa Maria Alvarez-Escobar ,  Julen Oyarzabal Santamarina ,  Frank Matthias Dautzenberg ,  Jacqueline Macritchie ,  Donald Simpson ,  Sonia Martinez Gonzalez

IPC分类号： A61K31/551 ,  A61K31/497 ,  C07D403/12 ,  A61P25/24 ,  A61P25/18 ,  C07D413/08 ,  A61K31/5377

CPC分类号： C07D241/20 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D491/10

摘要： The present invention concerns aryl and heteroaryl substituted pyrazinone derivatives having antagonistic melanin-concentrating hormone (MCH) activity, in particular MCH-1 activity according to the general Formula (I) a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, an N-oxide form thereof or a quaternary ammonium salt thereof, wherein the variables are defined in Claim 1. It further relates to their preparation, compositions comprising them and their use as a medicine. The compounds according to the invention are useful for the prevention and/or treatment of psychiatric disorders, including but not limited to anxiety, eating disorders, mood disorders, such as bipolar disorders and depression, psychoses, such as schizophrenia, and sleeping disorders; obesity; diabetes; sexual disorders and neurological disorders.

摘要翻译： 本发明涉及具有拮抗性黑色素浓缩激素（MCH）活性的芳基和杂芳基取代的吡嗪酮衍生物，特别是根据通式（I）的MCH-1活性，其药学上可接受的酸或碱加成盐，其立体化学异构形式 ，其N-氧化物形式或其季铵盐，其中所述变量在权利要求1中定义。它还涉及它们的制备，包含它们的组合物及其作为药物的用途。 根据本发明的化合物可用于预防和/或治疗精神病学障碍，包括但不限于焦虑，进食障碍，情绪障碍，例如双相性精神障碍和抑郁症，精神病如精神分裂症和睡眠障碍; 肥胖; 糖尿病; 性障碍和神经障碍。

公开(公告)号：US08841323B2

公开(公告)日：2014-09-23

申请号：US12282663

申请日：2007-03-15

申请人： Jose Maria Cid-Nunez ,  Jose Ignacio Andres-Gil ,  Andres Avelino Trabanco-Suarez ,  Julen Oyarzabal Santamarina ,  Frank Matthias Dautzenberg ,  Gregor James MacDonald ,  Shirley Elizabeth Pullan ,  Robert Johannes Lutjens ,  Guillaume Albert Jacques Duvey ,  Vanthea Nhem ,  Terry Patrick Finn ,  Gagik Melikyan ,  Vincent Mutel

发明人： Hassan Julien Imogai ,  Jose Maria Cid-Nunez ,  Jose Ignacio Andres-Gil ,  Andres Avelino Trabanco-Suarez ,  Julen Oyarzabal Santamarina ,  Frank Matthias Dautzenberg ,  Gregor James MacDonald ,  Shirley Elizabeth Pullan ,  Robert Johannes Lutjens ,  Guillaume Albert Jacques Duvey ,  Vanthea Nhem ,  Terry Patrick Finn ,  Gagik Melikyan

IPC分类号： A61K31/4439 ,  C07D213/85

CPC分类号： C07D213/85 ,  C07D213/84 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D409/04 ,  C07D413/04 ,  C07D413/10 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  C07D471/10 ,  C07D487/08 ,  C07D491/04 ,  C07D491/10 ,  C07D495/04

摘要： The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors-subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

摘要翻译： 本发明涉及新型化合物，特别是根据式（I）的新型吡啶酮衍生物，其中所有基团在申请和权利要求书中定义。 根据本发明的化合物是代谢型受体亚型2（“mGluR2”）的正性变构调节剂，其可用于治疗或预防与谷氨酸功能障碍相关的神经和精神障碍以及参与代谢型受体的mGluR2亚型的疾病 。 特别地，这些疾病是选自焦虑，精神分裂症，偏头痛，抑郁症和癫痫组的中枢神经系统疾病。 本发明还涉及制备这些化合物和组合物的药物组合物和方法，以及这些化合物用于预防和治疗其中涉及mGluR2的疾病的用途。

公开(公告)号：US20090281099A1

公开(公告)日：2009-11-12

申请号：US12301546

申请日：2007-05-21

申请人： José Ignacio Andrés-Gil ,  Manuel Jesús Alcázar-Vaca ,  Maria Lourdes Linares De La Morena ,  Sonia Martinez Gonzalez ,  Julen Oyarzabal Santamarina ,  Joaquin Pastor-Fernàndez ,  Juan Antonio Vega Ramiro ,  Francisca Delgado-Jiménez ,  Wilhelmus Helena Drinkenburg

发明人： José Ignacio Andrés-Gil ,  Manuel Jesús Alcázar-Vaca ,  Maria Lourdes Linares De La Morena ,  Sonia Martinez Gonzalez ,  Julen Oyarzabal Santamarina ,  Joaquin Pastor-Fernàndez ,  Juan Antonio Vega Ramiro ,  Francisca Delgado-Jiménez ,  Wilhelmus Helena Drinkenburg

IPC分类号： A61K31/5377 ,  A61K31/497 ,  C07D413/14 ,  C07D403/04 ,  C07D401/12

CPC分类号： C07D403/06 ,  C07D241/18 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14

摘要： The present invention concerns substituted pyrazinone derivatives according to the general Formula (I) a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, an N-oxide form thereof or a quaternary ammonium salt thereof, wherein the variables are defined in Claim 1, having selective α2C-adrenoceptor antagonist activity. It further relates to their preparation, compositions comprising them and their use as a medicine. The compounds according to the invention are usefull for the prevention and/or treatment of central nervous system disorders, mood disorders, anxiety disorders, stress-related disorders associated with depression and/or anxiety, cognitive disorders, personality disorders, schizoaffective disorders, Parkinson's disease, dementia of the Alzheimer's type, chronic pain conditions, neurodegenerative diseases, addiction disorders, mood disorders and sexual dysfunction.

摘要翻译： 本发明涉及根据通式（I）的取代的吡嗪酮衍生物，其药学上可接受的酸或碱加成盐，其立体化学异构形式，其N-氧化物形式或其季铵盐，其中变量定义于 权利要求1，具有选择性α2C-肾上腺素受体拮抗剂活性。 它还涉及它们的制备，包含它们的组合物及其作为药物的用途。 根据本发明的化合物可用于预防和/或治疗中枢神经系统疾病，情绪障碍，焦虑障碍，与抑郁和/或焦虑相关的压力相关疾病，认知障碍，人格障碍，分裂情感障碍，帕金森病 ，阿尔茨海默病的痴呆，慢性疼痛病症，神经变性疾病，成瘾症，情绪障碍和性功能障碍。

公开(公告)号：US20090111801A1

公开(公告)日：2009-04-30

申请号：US12297670

申请日：2007-04-19

申请人： Jose Ignacio Andres-Gil ,  Manuel Jesus Alcazar-Vaca ,  Maria Lourdes Linares De La Morena ,  Sonia Martinez Gonzalez ,  Julen Oyarzabal Santamarina ,  Joaquin Pastor-Fernandez ,  Juan Antonio Vega Ramiro ,  Francisca Delgado-Jimenez ,  Wilhelmus Helena Ignatius Maria Drinkenburg

发明人： Jose Ignacio Andres-Gil ,  Manuel Jesus Alcazar-Vaca ,  Maria Lourdes Linares De La Morena ,  Sonia Martinez Gonzalez ,  Julen Oyarzabal Santamarina ,  Joaquin Pastor-Fernandez ,  Juan Antonio Vega Ramiro ,  Francisca Delgado-Jimenez ,  Wilhelmus Helena Ignatius Maria Drinkenburg

IPC分类号： A61K31/538 ,  C07D401/14 ,  A61K31/497 ,  A61P25/00 ,  A61K31/5377 ,  C07D413/14

CPC分类号： C07D401/12 ,  C07D239/47 ,  C07D401/14 ,  C07D403/06 ,  C07D405/06 ,  C07D405/14 ,  C07D409/06 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/06 ,  C07D417/14

摘要： The present invention concerns substituted pyrazinone derivatives according to the general Formula (I), a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, an N-oxide form thereof or a quaternary ammonium salt thereof, wherein the variables are defined in Claim 1, having selective α2C-adrenoceptor antagonist activity. It further relates to their preparation, compositions comprising them and their use as a medicine. The compounds according to the invention are useful for the prevention and/or treatment of central nervous system disorders, mood disorders, anxiety disorders, stress-related disorders associated with depression and/or anxiety, cognitive disorders, personality disorders, schizoaffective disorders, Parkinson's disease, dementia of the Alzheimer's type, chronic pain conditions, neurodegenerative diseases, addiction disorders, mood disorders and sexual dysfunction.

摘要翻译： 本发明涉及根据通式（I）的取代的吡嗪酮衍生物，其药学上可接受的酸或碱加成盐，其立体化学异构形式，其N-氧化物形式或其季铵盐，其中定义了变量 在权利要求1中，具有选择性α2C-肾上腺素受体拮抗剂活性。 它还涉及它们的制备，包含它们的组合物及其作为药物的用途。 根据本发明的化合物可用于预防和/或治疗中枢神经系统疾病，情绪障碍，焦虑障碍，与抑郁和/或焦虑相关的压力相关疾病，认知障碍，人格障碍，分裂情感障碍，帕金森病 ，阿尔茨海默病的痴呆，慢性疼痛病症，神经变性疾病，成瘾症，情绪障碍和性功能障碍。

公开(公告)号：US09993554B2

公开(公告)日：2018-06-12

申请号：US13880893

申请日：2011-06-01

申请人： Manuel Serrano Marugan ,  Joaquin Pastor Fernández ,  Sonia Martínez González ,  Ana Ortega Molina ,  James R. Bischoff ,  Julen Oyarzabal Santamarina

发明人： Manuel Serrano Marugan ,  Joaquin Pastor Fernández ,  Sonia Martínez González ,  Ana Ortega Molina ,  James R. Bischoff ,  Julen Oyarzabal Santamarina

IPC分类号： A61K31/5377 ,  A61K31/35 ,  A61K45/06 ,  C07D471/10 ,  C07D487/04 ,  A61K31/4985

CPC分类号： A61K45/06 ,  A61K31/35 ,  A61K31/4985 ,  A61K31/5377 ,  C07D471/10 ,  C07D487/04

摘要： The first aspect of the invention relates to a phosphoinositide 3-kinase inhibitor for use in the treatment or prevention of a disease or condition associated with the expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (Pgd1α) and/or uncoupling protein 1 (Thermogenin/Ucp1) in brown adipocytes. The disease or condition may be positive energy imbalance-associated, for example, obesity, an obesity-associated disease or condition, steatosis and biological aging (performance aging). Another aspect of the invention provides the use of a phosphoinositide 3-kinase inhibitor for promoting weight loss in an individual.