公开(公告)号：US20140249141A1

公开(公告)日：2014-09-04

申请号：US14239817

申请日：2012-08-20

申请人： Anatoly Mazurov ,  Lan Miao ,  Todd Showalter

发明人： Anatoly Mazurov ,  Lan Miao ,  Todd Showalter

IPC分类号： C07D519/00 ,  A61K31/551

CPC分类号： C07D519/00 ,  A61K31/551 ,  C07D498/04

摘要： The present invention relates to compounds that bind to and modulate the activity of neuronal nicotinic acetylcholine receptors, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders, including inflammatory diseases and diseases associated with dysfunction of the central nervous system (CNS).

摘要翻译： 本发明涉及结合并调节神经元烟碱乙酰胆碱受体的活性，制备这些化合物的方法，含有这些化合物的药物组合物的化合物，以及使用这些化合物治疗各种各样的病症和疾病的方法， 包括与中枢神经系统（CNS）功能障碍相关的炎性疾病和疾病。

公开(公告)号：US08114889B2

公开(公告)日：2012-02-14

申请号：US12447850

申请日：2007-11-01

申请人： Anatoly Mazurov ,  Lan Miao ,  Yun-De Xiao

发明人： Anatoly Mazurov ,  Lan Miao ,  Yun-De Xiao

IPC分类号： A61K31/44

CPC分类号： C07D487/04 ,  C07D471/08

摘要： Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are amide compounds which can be prepared from certain heteoraryl carboxylic acids and certain diazabicycloalkanes. The compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the a4β2 subtype in the central nervous system (CNS). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly CNS disorders. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects, and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g. side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastrointestinal tract, and significant effects upon skeletal muscle).

摘要翻译： 公开了化合物，包括该化合物的药物组合物，及其制备和使用方法。 这些化合物是可以由某些芳香羧酸和某些二氮杂双环烷烃制备的酰胺化合物。 该化合物对中枢神经系统（CNS）中的a4和bgr2亚型的神经元烟碱受体具有选择性并且以高亲和力结合。 化合物和组合物可用于治疗和/或预防多种病症或病症，特别是CNS疾病。 化合物可以：（i）改变患者脑部烟碱性胆碱能受体的数量，（ii）显示出神经保护作用，和（iii）当以有效量使用时，不会产生明显的不良副作用 因为血压和心率的显着增加，对胃肠道的显着的负面影响和对骨骼肌的显着影响）。

公开(公告)号：US20100173932A1

公开(公告)日：2010-07-08

申请号：US12723790

申请日：2010-03-15

申请人： Anatoly Mazurov ,  Lan Miao ,  Yun-De Xiao ,  Philip S. Hammond ,  Craig H. Miller ,  Srinivisa Rao Akireddy ,  V. Srinivasa Murthy ,  Regina C. Whitaker ,  Scott R. Breining ,  Matt S. Melvin

发明人： Anatoly Mazurov ,  Lan Miao ,  Yun-De Xiao ,  Philip S. Hammond ,  Craig H. Miller ,  Srinivisa Rao Akireddy ,  V. Srinivasa Murthy ,  Regina C. Whitaker ,  Scott R. Breining ,  Matt S. Melvin

IPC分类号： A61K31/407 ,  C07D487/04 ,  C07D471/04 ,  A61K31/4375 ,  A61K31/4439 ,  A61K31/422 ,  A61P25/00 ,  A61P25/28 ,  A61P25/18

CPC分类号： C07D487/04 ,  C07D471/08

摘要： Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are amide compounds which can be prepared from certain heteroaryl carboxylic acids and certain diazabicycloalkanes. The compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the α4β2 subtype in the central nervous system (CNS). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly CNS disorders. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects, and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g. side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastrointestinal tract, and significant effects upon skeletal muscle).

摘要翻译： 公开了化合物，包括该化合物的药物组合物，及其制备和使用方法。 这些化合物是可以由某些杂芳基羧酸和某些二氮杂双环烷烃制备的酰胺化合物。 该化合物对中枢神经系统（CNS）中α4和bgr2亚型的神经元烟碱受体表现出选择性并且以高亲和力结合。 化合物和组合物可用于治疗和/或预防多种病症或病症，特别是CNS疾病。 化合物可以：（i）改变患者脑部烟碱性胆碱能受体的数量，（ii）显示出神经保护作用，和（iii）当以有效量使用时，不会产生明显的不良副作用 因为血压和心率的显着增加，对胃肠道的显着的负面影响和对骨骼肌的显着影响）。

公开(公告)号：US08859609B2

公开(公告)日：2014-10-14

申请号：US13342635

申请日：2012-01-03

申请人： Anatoly Mazurov ,  Lan Miao ,  Yunde Xiao

发明人： Anatoly Mazurov ,  Lan Miao ,  Yunde Xiao

IPC分类号： A61K31/40 ,  C07D471/08 ,  C07D487/04

CPC分类号： C07D487/04 ,  C07D471/08

摘要： Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are amide compounds which can be prepared from certain heteroaryl carboxylic acids and certain diazabicycloalkanes. The compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the α4β2 subtype in the central nervous system (CNS). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly CNS disorders. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects, and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g. side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastrointestinal tract, and significant effects upon skeletal muscle).

摘要翻译： 公开了化合物，包括该化合物的药物组合物，及其制备和使用方法。 这些化合物是可以由某些杂芳基羧酸和某些二氮杂双环烷烃制备的酰胺化合物。 该化合物对中枢神经系统（CNS）中α4和bgr2亚型的神经元烟碱受体表现出选择性并且以高亲和力结合。 化合物和组合物可用于治疗和/或预防多种病症或病症，特别是CNS疾病。 化合物可以：（i）改变患者脑部烟碱性胆碱能受体的数量，（ii）显示出神经保护作用，和（iii）当以有效量使用时，不会产生明显的不良副作用 因为血压和心率的显着增加，对胃肠道的显着的负面影响和对骨骼肌的显着影响）。

公开(公告)号：US20080242693A1

公开(公告)日：2008-10-02

申请号：US12123530

申请日：2008-05-20

申请人： Scott R. Breining ,  Balwinder S. Bhatti ,  Gregory D. Hawkins ,  Lan Miao ,  Anatoly Mazurov ,  Craig H. Miller

发明人： Scott R. Breining ,  Balwinder S. Bhatti ,  Gregory D. Hawkins ,  Lan Miao ,  Anatoly Mazurov ,  Craig H. Miller

IPC分类号： A61K31/439 ,  A61P25/30

CPC分类号： C07D221/22 ,  C07D401/04

摘要： Patients susceptible to or suffering from disorders, such as central nervous system disorders, which are characterized by an alteration in normal neurotransmitter release, such as dopamine release (e.g., Parkinsonism, Parkinson's Disease, Tourette's Syndrome, attention deficient disorder, or schizophrenia), are treated by administering a compound of Formulas 1 or 2, as described herein. The compounds of Formulas 1 and 2 are also useful for treating pain, and treating drug addiction, nicotine addiction, and/or obesity. The compounds can exist as individual stereoisomers, racemic mixtures, diastereomers and the like.

摘要翻译： 特征在于正常神经递质释放（如多巴胺释放（如帕金森综合征，帕金森氏病，图雷特氏综合征，注意缺陷障碍或精神分裂症））改变的中枢神经系统疾病易患或患有疾病的患者是 通过施用如本文所述的式1或2的化合物进行治疗。 式1和式2化合物也可用于治疗疼痛，治疗药物成瘾，尼古丁成瘾和/或肥胖症。 该化合物可作为单独的立体异构体，外消旋混合物，非对映异构体等存在。

公开(公告)号：US20070197579A1

公开(公告)日：2007-08-23

申请号：US11465914

申请日：2006-08-21

申请人： Anatoly Mazurov ,  Lan Miao ,  Jozef Klucik

发明人： Anatoly Mazurov ,  Lan Miao ,  Jozef Klucik

IPC分类号： A61K31/4745 ,  C07D471/14

CPC分类号： C07D471/18 ,  C07D471/14

摘要： The present invention relates to amide and urea derivatives of heteroaryl-substituted diazatricycloalkanes, pharmaceutical compositions including the compounds, methods of preparing the compounds, and methods of treatment using the compounds. More specifically, the methods of treatment involve modulating the activity of the α7 nAChR subtype by administering one or more of the compounds to treat or prevent disorders mediated by the α7 nAChR subtype. The diazatricycloalkanes typically consist of a 1-azabicyclooctane fused to pyrrolidine ring. The substitutent heteroaryl groups are 5- or 6-membered ring heteroaromatics, such as 3-pyridinyl and 5-pyrimidinyl moieties, which are attached directly to the diazatricycloalkane. The secondary nitrogen of the pyrrolidine moiety is substituted with an arylcarbonyl (amide type derivative) or an arylaminocarbonyl (N-arylcarbamoyl) (urea type derivative) group. The compounds are beneficial in therapeutic applications requiring a selective interaction at certain nAChR subtypes. That is, the compounds modulate the activity of certain nAChR subtypes, particularly the α7 nAChR subtype, and do not have appreciable activity toward muscarinic receptors. Radiolabeled versions of the compounds can be used in diagnostic methods.

摘要翻译： 本发明涉及杂芳基取代的二氮三环环烷烃的酰胺和脲衍生物，包括该化合物的药物组合物，制备该化合物的方法和使用该化合物的治疗方法。 更具体地，治疗方法包括通过施用一种或多种化合物来治疗或预防由α7nAChR亚型介导的病症来调节α7nAChR亚型的活性。 二氮杂环烷烃通常由与吡咯烷环稠合的1-氮杂双环辛烷组成。 取代基杂芳基是直接连接到二氮杂环烷烃上的5-或6-元环杂芳族化合物，例如3-吡啶基和5-嘧啶基部分。 吡咯烷部分的仲氮被芳基羰基（酰胺型衍生物）或芳基氨基羰基（N-芳基氨基甲酰基）（脲型衍生物）基团取代。 这些化合物在需要在某些nAChR亚型选择性相互作用的治疗应用中是有益的。 也就是说，化合物调节某些nAChR亚型，特别是α7nAChR亚型的活性，并且对毒蕈碱受体没有明显的活性。 化合物的放射性标记版本可用于诊断方法。

公开(公告)号：US20120289572A1

公开(公告)日：2012-11-15

申请号：US13555458

申请日：2012-07-23

申请人： Anatoly Mazurov ,  Lan Miao ,  Yun-De Xiao

发明人： Anatoly Mazurov ,  Lan Miao ,  Yun-De Xiao

IPC分类号： A61K31/407 ,  A61P25/18 ,  A61P25/08 ,  A61P25/14 ,  A61P25/00 ,  A61P25/28 ,  A61P25/16

CPC分类号： C07D487/04 ,  C07D471/08

摘要： Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are amide compounds which can be prepared from certain heteroaryl carboxylic acids and certain diazabicycloalkanes. The compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the α4β2 subtype in the central nervous system (CNS). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly CNS disorders. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects, and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g. side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastrointestinal tract, and significant effects upon skeletal muscle).

摘要翻译： 公开了化合物，包括该化合物的药物组合物，及其制备和使用方法。 这些化合物是可以由某些杂芳基羧酸和某些二氮杂双环烷烃制备的酰胺化合物。 该化合物对中枢神经系统（CNS）中α4和bgr2亚型的神经元烟碱受体表现出选择性并且以高亲和力结合。 化合物和组合物可用于治疗和/或预防多种病症或病症，特别是CNS疾病。 化合物可以：（i）改变患者脑部烟碱性胆碱能受体的数量，（ii）显示神经保护作用，和（iii）当以有效量使用时，不会产生明显的副作用（例如副作用 因为血压和心率的显着增加，对胃肠道的显着的负面影响和对骨骼肌的显着影响）。

公开(公告)号：US07732607B2

公开(公告)日：2010-06-08

申请号：US11465914

申请日：2006-08-21

申请人： Anatoly Mazurov ,  Lan Miao ,  Jozef Klucik

发明人： Anatoly Mazurov ,  Lan Miao ,  Jozef Klucik

IPC分类号： C07D471/18 ,  A61K31/439 ,  A61K31/437

CPC分类号： C07D471/18 ,  C07D471/14

摘要： The present invention relates to amide and urea derivatives of heteroaryl-substituted diazatricycloalkanes, pharmaceutical compositions including the compounds, methods of preparing the compounds, and methods of treatment using the compounds. More specifically, the methods of treatment involve modulating the activity of the α7 nAChR subtype by administering one or more of the compounds to treat or prevent disorders mediated by the α7 nAChR subtype. The diazatricycloalkanes typically consist of a 1-azabicyclooctane fused to pyrrolidine ring. The substitutent heteroaryl groups are 5- or 6-membered ring heteroaromatics, such as 3-pyridinyl and 5-pyrimidinyl moieties, which are attached directly to the diazatricycloalkane. The secondary nitrogen of the pyrrolidine moiety is substituted with an arylcarbonyl (amide type derivative) or an arylaminocarbonyl (N-arylcarbamoyl) (urea type derivative) group. The compounds are beneficial in therapeutic applications requiring a selective interaction at certain nAChR subtypes. That is, the compounds modulate the activity of certain nAChR subtypes, particularly the α7 nAChR subtype, and do not have appreciable activity toward muscarinic receptors. Radiolabeled versions of the compounds can be used in diagnostic methods.

摘要翻译： 本发明涉及杂芳基取代的二氮三环环烷烃的酰胺和脲衍生物，包括该化合物的药物组合物，制备该化合物的方法和使用该化合物的治疗方法。 更具体地，治疗方法包括通过施用一种或多种化合物来治疗或预防由α7nAChR亚型介导的疾病来调节α7nAChR亚型的活性。 二氮杂环烷烃通常由与吡咯烷环稠合的1-氮杂双环辛烷组成。 取代基杂芳基是直接连接到二氮杂环烷烃上的5-或6-元环杂芳族化合物，例如3-吡啶基和5-嘧啶基部分。 吡咯烷部分的仲氮被芳基羰基（酰胺型衍生物）或芳基氨基羰基（N-芳基氨基甲酰基）（脲型衍生物）基团取代。 这些化合物在需要在某些nAChR亚型选择性相互作用的治疗应用中是有益的。 也就是说，化合物调节某些nAChR亚型，特别是α7nAChR亚型的活性，并且对毒蕈碱受体没有明显的活性。 化合物的放射性标记版本可用于诊断方法。

公开(公告)号：US08476296B2

公开(公告)日：2013-07-02

申请号：US12740970

申请日：2010-01-25

申请人： Merouane Bencherif ,  Nikolai Fedorov ,  Terry Hauser ,  Kristen Jordan ,  Sharon Rae Letchworth ,  Anatoly Mazurov ,  Julio A. Munoz ,  Jason Speake ,  Daniel Yohannes

发明人： Merouane Bencherif ,  Nikolai Fedorov ,  Terry Hauser ,  Kristen Jordan ,  Sharon Rae Letchworth ,  Anatoly Mazurov ,  Julio A. Munoz ,  Jason Speake ,  Daniel Yohannes

IPC分类号： A01N43/90 ,  A61K31/44 ,  C07D451/00 ,  C07D453/02

CPC分类号： A61K31/444 ,  C07D453/02

摘要： The present invention relates to compounds that bind to and modulate the activity of neuronal nicotinic acetylcholine receptors, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central nervous system (CNS).

摘要翻译： 本发明涉及结合并调节神经元烟碱乙酰胆碱受体的活性，制备这些化合物的方法，含有这些化合物的药物组合物的化合物，以及使用这些化合物治疗各种各样的病症和疾病的方法， 包括与中枢神经系统（CNS）功能障碍相关的那些。

公开(公告)号：US20120053168A1

公开(公告)日：2012-03-01

申请号：US13148385

申请日：2010-02-16

申请人： Balwinder Singh Bhatti ,  Timothy J. Cuthbertson ,  Anatoly Mazurov ,  Joseph Pike Mitchener ,  Julio A. Munoz ,  Srinivasa V. Murthy ,  Yunde Xiao ,  Daniel Yohannes

发明人： Balwinder Singh Bhatti ,  Timothy J. Cuthbertson ,  Anatoly Mazurov ,  Joseph Pike Mitchener ,  Julio A. Munoz ,  Srinivasa V. Murthy ,  Yunde Xiao ,  Daniel Yohannes

IPC分类号： A61K31/55 ,  C07D471/04 ,  C07D223/16 ,  A61P25/28 ,  A61P25/00 ,  A61P9/10 ,  A61P25/18 ,  A61P25/16 ,  A61P25/14 ,  A61P29/00 ,  A61P25/08 ,  A61P25/22 ,  A61P25/24 ,  A61P3/04 ,  A61P25/30 ,  A61P25/32 ,  A61P25/34 ,  A61P25/04 ,  C07D487/04

CPC分类号： C07D487/04 ,  A61K31/4985 ,  C07D223/14 ,  C07D241/36

摘要： The present invention relates to compounds that bind to and modulate the activity of neuronal nicotinic acetylcholine receptors, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central nervous system (CNS).

摘要翻译： 本发明涉及结合并调节神经元烟碱乙酰胆碱受体的活性，制备这些化合物的方法，含有这些化合物的药物组合物的化合物，以及使用这些化合物治疗各种各样的病症和疾病的方法， 包括与中枢神经系统（CNS）功能障碍相关的那些。