公开(公告)号：US20080269251A1

公开(公告)日：2008-10-30

申请号：US12091181

申请日：2006-12-18

申请人： Jose Ignacio Andre-Gil ,  Manuel Jesus Alcazar-Vaca ,  Maria Lourdes De La Morena ,  Sonio Martinez Gonzalez ,  Julen Oyarzabal Santanarina ,  Joaquin Pastor-Fernandez ,  Juan Antonio Vega Ramiro ,  Wilhelmus Helena Ignatius Maria Drinkenburg

发明人： Jose Ignacio Andre-Gil ,  Manuel Jesus Alcazar-Vaca ,  Maria Lourdes De La Morena ,  Sonio Martinez Gonzalez ,  Julen Oyarzabal Santanarina ,  Joaquin Pastor-Fernandez ,  Juan Antonio Vega Ramiro ,  Wilhelmus Helena Ignatius Maria Drinkenburg

IPC分类号： A61K31/497 ,  C07D403/06 ,  A61P25/24 ,  A61P25/18 ,  A61P25/04 ,  A61P25/28 ,  A61P25/00

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

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，其中变量定义于 权利要求1，具有选择性α2-2肾上腺素能受体拮抗剂活性。 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：US20080113988A1

公开(公告)日：2008-05-15

申请号：US11791510

申请日：2005-11-25

申请人： Jose Ignacio Andres-Gil ,  Jose Manuel Bartolome-Nebreda ,  Manuel Jesus Alcazar-Vaca ,  Maria de las Mercedes Garcia-Martin ,  Antonius Adrianus Hendrikus Petrus Megens

发明人： Jose Ignacio Andres-Gil ,  Jose Manuel Bartolome-Nebreda ,  Manuel Jesus Alcazar-Vaca ,  Maria de las Mercedes Garcia-Martin ,  Antonius Adrianus Hendrikus Petrus Megens

IPC分类号： C07D413/00 ,  A61K31/5377 ,  A61K31/4439 ,  A61K31/454 ,  A61P25/00

CPC分类号： C07D498/04

摘要： The present invention relates to novel isoxazoline-indole derivatives according to 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, with a binding affinity towards dopamine receptors, in particular towards dopamine D2 and/or D3 receptors, with selective serotonin reuptake inhibition (SSRI) properties and showing an affinity for the 5-HT1A receptor, pharmaceutical compositions comprising the compounds according to the invention, the use thereof for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic disorders, most in particular schizophrenia and processes for their production, wherein the variables are further defined in the application.

摘要翻译： 本发明涉及具有结合亲和力的式（I）的异恶唑啉 - 吲哚衍生物，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 朝向多巴胺受体，特别是多巴胺D 2和/或D 3受体，具有选择性5-羟色胺再摄取抑制（SSRI）特性，并显示出对5-HT 包含本发明化合物的药物组合物，其用于预防和/或治疗一系列精神和神经障碍，特别是某些精神病性疾病，特别是精神分裂症和过程的用途 用于其生产，其中在应用中进一步定义变量。

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：US20060142318A1

公开(公告)日：2006-06-29

申请号：US11355402

申请日：2006-02-16

申请人： Kristol Emelen ,  Marcel Frans De Bruyn ,  Manuel Jesus Alcazar-Vaca ,  Jose Andres-Gil ,  Francisco Femandez-Gadea ,  Maria Malesanz-Ballesteros ,  Jose Bartolome-Nebreda

发明人： Kristol Emelen ,  Marcel Frans De Bruyn ,  Manuel Jesus Alcazar-Vaca ,  Jose Andres-Gil ,  Francisco Femandez-Gadea ,  Maria Malesanz-Ballesteros ,  Jose Bartolome-Nebreda

IPC分类号： A61K31/513 ,  C07D403/02

CPC分类号： C07D411/04 ,  C07D491/04

摘要： The present invention concerns compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, wherein -a1=a2-a3=a4- is a bivalent radical wherein one or two of a1 to a4 are nitrogen and the remaining a1 to a4 are —CH═; -Z1-Z2- is a bivalent radical; -A- is a bivalent radical of formula —N(R6)-Alk2- or a 5, 6 or 7-membered saturated heterocycle containing one or two nitrogen atoms; R1, R2 and R3 are each independently selected from hydrogen, C1-6alkyl, hydroxy, halo and the like; Alk1 and Alk2 are optionally substituted C1-6alkanediyl; R5 is a radical of formula wherein n is 1 or 2; p1 is 0, and p2 is 1 or 2; or p1 is 1 or 2, and p2 is 0; X is oxygen, sulfur or ═NR9; Y2 is oxygen or sulfur; R7 is hydrogen, C1-6alkyl, C3-6cycloalkyl, phenyl or phenylmethyl; R8 is C1-6alkyl, C3-6cycloalkyl phenyl or phenylmethyl; R9 is cyano, C1-6alkyl, C3-6cycloalkyl, C1-6alkyloxycarbonyl or aminocarbonyl; R10 is hydrogen or C1-6alkyl; and Q is a bivalent radical. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to disturbed fundic accomodation.

公开(公告)号：US20100035909A1

公开(公告)日：2010-02-11

申请号：US12444878

申请日：2007-12-04

申请人： Jose Ignacio Andres-Gil ,  Manuel Jesus Alcazar-Vaca ,  Frank Matthias Dautzenberg ,  Joannes Theodorus Maria Linders

发明人： Jose Ignacio Andres-Gil ,  Manuel Jesus Alcazar-Vaca ,  Frank Matthias Dautzenberg ,  Joannes Theodorus Maria Linders

IPC分类号： A61K31/438 ,  C07D215/02 ,  A61P25/18 ,  A61P25/22 ,  A61P3/10 ,  A61P25/24

CPC分类号： C07D471/10 ,  C07D498/10

摘要： The present invention concerns aryl and heteroaryl substituted diaza-spiro-pyridinone 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, 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二氮 - 螺 - 吡啶酮衍生物，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。其还涉及其制备方法，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。