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1. 发明申请

US20110263629A1 AMIDES OF DIAZABICYCLOOCTANES AND USES THEREOF 审中-公开
标题翻译：双酚A的氨基酸及其用途
公开(公告)号：US20110263629A1
公开(公告)日：2011-10-27
申请号：US13061972
申请日：2009-09-02
申请人： Jon-Paul Strachan , Balwinder Singh Bhatti , Anatoly Mazurov , Jozef Klucik , Yunde Xiao , Philip S. Hammond , David Kombo , Lan Miao , Jason Daniel Speake , Daniel Yohannes
发明人： Jon-Paul Strachan , Balwinder Singh Bhatti , Anatoly Mazurov , Jozef Klucik , Yunde Xiao , Philip S. Hammond , David Kombo , Lan Miao , Jason Daniel Speake , Daniel Yohannes
IPC分类号： A61K31/439 , A61P25/00 , A61P25/28 , A61P25/18 , A61P3/04 , A61P3/00 , A61P37/06 , A61P25/30 , A61P25/04 , C07D471/08 , A61P29/00
CPC分类号： C07D471/08
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。

2. 发明申请

US20140288169A1 NICOTINIC RECEPTOR NON-COMPETITIVE ANTAGONISTS 审中-公开
标题翻译： NICOTINIC RECEPTOR非竞争性拮抗剂
公开(公告)号：US20140288169A1
公开(公告)日：2014-09-25
申请号：US13978583
申请日：2012-01-05
申请人： Srinivasa Rao Akireddy , Scott R. Breining , Matt S. Melvin , Srinivasa V. Murthy , Anatoly A. Mazurov , Balwinder Singh Bhatti , Jon-Paul Strachan , Ronald Joseph Heemstra , Todd Showalter , Yunde Xiao , Philip S. Hammond , Lan Miao , David Kombo , Daniel Yohannes , Jason Speake
发明人： Srinivasa Rao Akireddy , Scott R. Breining , Matt S. Melvin , Srinivasa V. Murthy , Anatoly A. Mazurov , Balwinder Singh Bhatti , Jon-Paul Strachan , Ronald Joseph Heemstra , Todd Showalter , Yunde Xiao , Philip S. Hammond , Lan Miao , David Kombo , Daniel Yohannes , Jason Speake
IPC分类号： C07D493/08 , C07C211/38
CPC分类号： C07D493/08 , C07C211/38 , C07C2602/40 , C07C2602/42 , C07C2602/44
摘要： The present invention relates to compounds that modulate nicotinic receptors as non-competitive antagonists, methods for their synthesis, methods for their use, and their pharmaceutical compositions.
摘要翻译：本发明涉及将烟碱受体调节为非竞争性拮抗剂的化合物，其合成方法，其使用方法及其药物组合物。

3. 发明申请

US20110071180A1 SUB-TYPE SELECTIVE AMIDES OF DIAZABICYCLOALKANES 审中-公开
标题翻译：亚类型的亚型选择性氨基酸
公开(公告)号：US20110071180A1
公开(公告)日：2011-03-24
申请号：US12919970
申请日：2009-03-04
申请人： Srinivasa Rao Akireddy , Balwinder Singh Bhatti , Scott R. Breining , Philip S. Hammond , Ronald Joseph Heemstra , Anatoly A. Mazurov , Matt S. Melvin , Lan Miao , V. Srinivasa Murthy , Jon-Paul Strachan , Yunde Xiao
发明人： Srinivasa Rao Akireddy , Balwinder Singh Bhatti , Scott R. Breining , Philip S. Hammond , Ronald Joseph Heemstra , Anatoly A. Mazurov , Matt S. Melvin , Lan Miao , V. Srinivasa Murthy , Jon-Paul Strachan , Yunde Xiao
IPC分类号： A61K31/439 , C07D487/04 , C07D471/08 , A61K31/407 , A61K31/4439 , A61P25/00 , A61P25/28 , A61P25/18
CPC分类号： C07D471/08
摘要： The present invention relates to compounds of the following formula (I) 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活性的下式（I）化合物，制备这些化合物的方法，含有这些化合物的药物组合物，以及使用这些化合物治疗各种各样的病症和疾病，包括与中枢神经系统（CNS）功能障碍有关的疾病。

4. 发明申请

US20100144700A1 HETEROCYCLIC-CARBONYL-DIAZABICYCLOALKANES AS MODULATORS OF THE NEURONAL NICOTINIC ACETYLCHOLINE ALPHA 4 BETA 2, SUBTYPE RECEPTOR FOR THE TREATMENT OF CNS RELATED DISORDERS 审中-公开
标题翻译：作为神经细胞性乙酰胆碱酯酶4β2的调节剂的杂环碳二亚氨基二醇，用于治疗CNS相关疾病的亚型受体
公开(公告)号：US20100144700A1
公开(公告)日：2010-06-10
申请号：US12530997
申请日：2008-03-12
申请人： Philip S. Hammond , Anatoly A. Mazurov , Lan Miao , Yun-De Xiao , Balwinder Singh Bhatti , Jon-Paul Strachan , V. Srinivasa Murthy , David C. Kombo , Srinivisa Rao Akireddy
发明人： Philip S. Hammond , Anatoly A. Mazurov , Lan Miao , Yun-De Xiao , Balwinder Singh Bhatti , Jon-Paul Strachan , V. Srinivasa Murthy , David C. Kombo , Srinivisa Rao Akireddy
IPC分类号： A61K31/439 , C07D471/08 , C07D487/04 , C07D471/04 , A61K31/407 , A61K31/422 , A61K31/437 , A61K31/4353 , A61P25/00 , A61P25/28 , A61P25/18
CPC分类号： C07D487/04 , C07D471/04 , C07D471/08
摘要： A compound of Formula 1: A-C(O)-Cy, wherein A is a diazabicyclic core, containing 7, 8, or 9 ring atoms, and selected from the following: 2,6-diazabicyclo[3.2.0]heptane; 3,6-diazabicyclo[3.ZO]heptane; 2,7-diazabicyclo[4.2.0]octane; 3,7-diazabicyclo[4.2.0]octane; 3,8-diazabicyclo[4.2.0]octane; 2,7-diazabicyclo[3.3.0]octane; 2,7-diazbicyclo[4.3.0]nonane; 2,8-diazbicyclo[4.3.0]nonane; 3,7-diazabicyclo[4.3.0]nonane; 3,8-diazabicyclo[4.3.0]nonane; 3,9-diazabicyclo[4.3.0]nonane; 2,6-diazabicyclo[3.2.1]octane; 3,6-diazabicyclo[3.2.1]octane; wherein the diazabicycle is attached as a radical to the depicted carbonyl via either one of the two ring nitrogen atoms, such that the carbonyl forms an amide bond with the ring nitrogen; Cy is a heteroaryl group; The compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the α402 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 are believed to: (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, namely 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：式1的化合物：A-C（O）-Cy，其中A是具有7,8或9个环原子的二氮杂双环核心，并且选自以下：2,6-二氮杂双环[3.2.0]庚烷; 3,6-二氮杂双环[3.ZO]庚烷; 2,7-二氮杂双环[4.2.0]辛烷; 3,7-二氮杂双环[4.2.0]辛烷; 3,8-二氮杂双环[4.2.0]辛烷; 2,7-二氮杂双环[3.3.0]辛烷; 2,7-二氮杂双环[4.3.0]壬烷; 2,8-二氮杂双环[4.3.0]壬烷; 3,7-二氮杂双环[4.3.0]壬烷; 3,8-二氮杂双环[4.3.0]壬烷; 3,9-二氮杂双环[4.3.0]壬烷; 2,6-二氮杂双环[3.2.1]辛烷; 3,6-二氮杂双环[3.2.1]辛烷; 其中所述二氮杂双环通过两个环氮原子中的任一个连接到所描绘的羰基上，使得羰基与环氮形成酰胺键; Cy是杂芳基; 该化合物对中枢神经系统（CNS）中α402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。这些化合物被认为是：（i）改变患者脑部烟碱性胆碱能受体的数量，（ii）表现出神经保护作用，和（iii）当以有效量使用时，不会产生明显的不利副作用影响如血压和心率显着升高，对胃肠道的显着负面影响，以及对骨骼肌的显着影响。

5. 发明申请

US20110257168A1 DERIVATIVES OF OXABISPIDINE AS NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS 审中-公开
标题翻译：奥昔布星作为神经激素乙酰胆碱受体配体的衍生物
公开(公告)号：US20110257168A1
公开(公告)日：2011-10-20
申请号：US13055085
申请日：2009-07-01
申请人： Srinivasa R. Akireddy , Scott R. Breining , Nikolai Fedorov , David Kombo , Anatoly A. Mazurov , Lan Miao , Srinivasa V. Murthy , Todd Showalter , Yunde Xiao , Daniel Yohannes
发明人： Srinivasa R. Akireddy , Scott R. Breining , Nikolai Fedorov , David Kombo , Anatoly A. Mazurov , Lan Miao , Srinivasa V. Murthy , Todd Showalter , Yunde Xiao , Daniel Yohannes
IPC分类号： A61K31/5383 , A61P29/00 , C07D498/04
CPC分类号： C07D498/04
摘要： The present invention relates to compounds of formula (I) 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的式（I）化合物，含有这些化合物的药物组合物，以及使用这些化合物治疗多种多样的方法的病症和障碍，包括与中枢神经系统（CNS）功能障碍相关的疾病。

6. 发明授权

US07897611B2 Pharmaceutical compositions and methods for relieving pain and treating central nervous system disorders 失效
标题翻译：用于缓解疼痛和治疗中枢神经系统疾病的药物组合物和方法
公开(公告)号：US07897611B2
公开(公告)日：2011-03-01
申请号：US12714014
申请日：2010-02-26
申请人： Balwinder Singh Bhatti , Scott R. Breining , Gregory D. Hawkins , Anatoly Mazurov , Lan Miao , Craig Harrison Miller , Teresa Y. Phillips
发明人： Balwinder Singh Bhatti , Scott R. Breining , Gregory D. Hawkins , Anatoly Mazurov , Lan Miao , Craig Harrison Miller , Teresa Y. Phillips
IPC分类号： A61K31/439 , C07D221/22
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。

7. 发明授权

US07732607B2 Heteroaryl-substituted diazatricycloalkanes and methods of use thereof 失效
标题翻译：杂芳基取代的二氮三环环烷烃及其使用方法
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。

8. 发明申请

US20070197579A1 Heteroaryl-Substituted Diazatricycloalkanes and Methods of Use Thereof 失效
标题翻译：杂芳基取代的二氮杂环烷烃及其使用方法
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。

9. 发明申请

US20100197720A1 HETEROARYL-SUBSTITUTED DIAZATRICYCLOALKANES AND METHODS OF USE THEREOF 审中-公开
标题翻译：异丙基取代的二氮杂环戊烷及其使用方法
公开(公告)号：US20100197720A1
公开(公告)日：2010-08-05
申请号：US12755799
申请日：2010-04-07
申请人： Anatoly Mazurov , Lan Miao , Jozef Klucik
发明人： Anatoly Mazurov , Lan Miao , Jozef Klucik
IPC分类号： A61K31/439 , C07D471/18
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 substituent 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5-或6-元环杂芳族化合物，例如3-吡啶基和5-嘧啶基部分，其直接连接到二氮杂环烷烃上。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。

10. 发明申请

US20060247270A1 3-Substituted-2(Arylalkyl)-1-Azabicycloalkanes and Methods of Use Thereof 有权
标题翻译： 3-取代的2（芳基烷基）-1-氮杂双环烷烃及其使用方法
公开(公告)号：US20060247270A1
公开(公告)日：2006-11-02
申请号：US11458231
申请日：2006-07-18
申请人： Anatoly Mazurov , Jozef Klucik , Lan Miao , Angela Seamans , Teresa Phillips , Jeffrey Schmitt , Craig Miller
发明人： Anatoly Mazurov , Jozef Klucik , Lan Miao , Angela Seamans , Teresa Phillips , Jeffrey Schmitt , Craig Miller
IPC分类号： A61K31/4745 , A61K31/407 , C07D453/02 , C07D487/02
CPC分类号： C07D471/08 , A61K51/0455 , C07D453/02 , C07D487/08
摘要： The present invention relates to 3-substituted-2-(arylalkyl)-1-azabicycloalkanes, methods of preparing the compounds and methods of treatment using the compounds. The azabicycloalkanes generally are azabicycloheptanes, azabicyclooctanes, or azabicyclononanes. The aryl group in the arylalkyl moiety is a 5- or 6-membered ring heteroaromatic, preferably 3-pyridinyl and 5-pyrimidinyl moieties, and the alkyl group is typically a C1-4 alkyl. The substituent at the 3-position of the 1-azabicycloalkane is a carbonyl group-containing moiety, such as an amide, carbamate, urea, thioamide, thiocarbamate, thiourea or similar functionality. The compounds exhibit activity at nicotinic acetylcholine receptors (nAChRs), particularly the α7 nAChR subtype, and are useful towards modulating neurotransmission and the release of ligands involved in neurotransmission. Methods for preventing or treating conditions and disorders, including central nervous system (CNS) disorders, which are characterized by an alteration in normal neurotransmission, are also disclosed. Also disclosed are methods for treating inflammation, autoimmune disorders, pain and excess neovascularization, such as that associated with tumor growth.
摘要翻译：本发明涉及3-取代-2-（芳基烷基）-1-氮杂双环烷烃，制备化合物的方法和使用该化合物的处理方法。氮杂双环烷烃通常是氮杂双环庚烷，氮杂双环辛烷或氮杂双环壬烷。芳烷基部分中的芳基是5-或6-元环杂芳族，优选3-吡啶基和5-嘧啶基部分，并且烷基通常是C 1-4烷基。 1-氮杂双环烷烃3-位上的取代基是含羰基的部分，例如酰胺，氨基甲酸酯，脲，硫代酰胺，硫代氨基甲酸酯，硫脲或类似官能团。该化合物在烟碱乙酰胆碱受体（nAChRs），特别是α7nAChR亚型中表现出活性，并且可用于调节神经传递和涉及神经传递的配体释放。还公开了预防或治疗包括中枢神经系统（CNS）病症在内的病症和障碍的方法，其特征在于正常神经传递的改变。还公开了用于治疗炎症，自身免疫疾病，疼痛和过量新生血管形成（例如与肿瘤生长相关的）的方法。

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