公开(公告)号：US20100121061A1

公开(公告)日：2010-05-13

申请号：US12633308

申请日：2009-12-08

Applicant: William S. Caldwell ,  Gary M. Dull ,  Balwinder S. Bhatti ,  Srishailkumar B. Hadimani ,  Haeil Park ,  Jared M. Wagner ,  Peter A. Crooks ,  Patrick M. Lippiello ,  Merouane Bencherif

Inventor： William S. Caldwell ,  Gary M. Dull ,  Balwinder S. Bhatti ,  Srishailkumar B. Hadimani ,  Haeil Park ,  Jared M. Wagner ,  Peter A. Crooks ,  Patrick M. Lippiello ,  Merouane Bencherif

IPC: C07D239/26 ,  C07D213/55 ,  C07D213/65 ,  C07D213/73 ,  C07D213/02

CPC classification number: C07D239/26 ,  A61K31/44 ,  A61K31/505 ,  C07D213/38 ,  C07D213/61 ,  C07D213/65 ,  C07D213/73 ,  C07D403/06

Abstract: The present invention generally relates to nicotinic compounds, in the form of aryl substituted olefinic compounds, as well as pro-drug, N-oxide, metabolite and pharmaceutically acceptable salt forms thereof. Methods of modulating neurotransmitter release via administration of the compounds, pro-drugs, N-oxides and/or pharmaceutically acceptable salts are also disclosed.

Abstract translation: 本发明一般涉及以芳基取代的烯属化合物形式的烟碱化合物，以及前药，N-氧化物，代谢产物和药学上可接受的盐形式。 还公开了通过施用化合物，前药，N-氧化物和/或药学上可接受的盐调节神经递质释放的方法。

公开(公告)号：US07045538B2

公开(公告)日：2006-05-16

申请号：US10971543

申请日：2004-10-22

Applicant: William S. Caldwell ,  Gary M. Dull ,  Balwinder S. Bhatti ,  Srishailkumar B. Hadimani ,  Haeil Park ,  Jared M. Wagner ,  Peter A. Crooks ,  Patrick M. Lippiello ,  Merouane Bencherif

Inventor： William S. Caldwell ,  Gary M. Dull ,  Balwinder S. Bhatti ,  Srishailkumar B. Hadimani ,  Haeil Park ,  Jared M. Wagner ,  Peter A. Crooks ,  Patrick M. Lippiello ,  Merouane Bencherif

IPC: C07D213/38 ,  A61K31/44 ,  A61P29/02

CPC classification number: C07D239/26 ,  A61K31/44 ,  A61K31/505 ,  C07D213/38 ,  C07D213/61 ,  C07D213/65 ,  C07D213/73 ,  C07D403/06

Abstract: The present invention generally relates to nicotinic compounds, in the form of aryl substituted olefinic compounds, as well as pro-drug, N-oxide, metabolite and pharmaceutically acceptable salt forms thereof. Methods of modulating neurotransmitter release via administration of the compounds, pro-drugs, N-oxides and/or pharmaceutically acceptable salts are also disclosed.

公开(公告)号：US06218383B1

公开(公告)日：2001-04-17

申请号：US09130498

申请日：1998-08-07

Applicant: Merouane Bencherif

Inventor： Merouane Bencherif

IPC: A61K3155

CPC classification number: A61K45/06 ,  A61K31/465 ,  A61K31/4706 ,  A61K2300/00

Abstract: A pharmaceutical composition incorporates a pharmaceutically effective amount of at least two components, one of those components being a nicotinic compound capable of interacting with nicotinic cholinergic receptors (e.g., a nicotinic agonist, such as E-metanicotine) and one of those components being an acetylcholinesterase inhibitor (e.g., tacrine). The pharmaceutical composition is useful for treating CNS disorders, such as Alzheimer's disease.

Abstract translation: 药物组合物包含药学上有效量的至少两种组分，其中一种组分是能够与烟碱性胆碱能受体（例如，烟碱型激动剂，例如E-间苯三酚）相互作用的烟碱化合物，其中一种组分是乙酰胆碱酯酶 抑制剂（如他克林）。 该药物组合物可用于治疗CNS疾病如阿尔茨海默病。

公开(公告)号：US5824692A

公开(公告)日：1998-10-20

申请号：US364977

申请日：1995-01-06

Applicant: Patrick Michael Lippiello ,  Merouane Bencherif ,  William Scott Caldwell ,  Gary Maurice Dull

Inventor： Patrick Michael Lippiello ,  Merouane Bencherif ,  William Scott Caldwell ,  Gary Maurice Dull

IPC: A61K31/44 ,  A61K31/4406 ,  A61K31/505 ,  C07D213/65 ,  C07D239/26

CPC classification number: C07D239/26 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/505 ,  C07D213/65

Abstract: Patients susceptible to or suffering from central nervous system disorders (e.g., neurodegenerative diseases including presenile dementia, senile dementia of the Alzeimer's type, and Parkinsonism including Parkinson's disease) are treated by administering an effective amount of an aryl substituted aliphatic compound, an aryl substituted olefinic amine compound or an aryl substituted acetylenic compound. Exemplary compounds are (E)-4-(5-pyrimidinyl)-3-butene-1-amine, (E)-4-�3-(5-methoxypyridin)yl!-3-butene-1-amine, (E)-N-methyl-4-(5-pyrimidinyl)-3-butene-1-amine, (E)-N-methyl-4-�3-(5-methoxypyrindin)yl!-3-butene-1-amine, (Z)-metanicotine, N-methyl-(3-pyridinyl)-butane-1-amine, N-methyl-4-(3-pyridinyl)-3-butyne-1-amine and (E)-N-methyl-4-�3-(6-methylpyrindin)yl!-3-butene-1-amine.

Abstract translation: 通过施用有效量的芳基取代的脂族化合物，芳基取代的烯属化合物来治疗患有中枢神经系统疾病（例如，老年性痴呆，阿尔茨海默型老年性痴呆和帕金森病的神经变性疾病）和患有帕金森综合征的帕金森病的患者 胺化合物或芳基取代的炔属化合物。 示例性化合物是（E）-4-（5-嘧啶基）-3-丁烯-1-胺，（E）-4- [3-（5-甲氧基吡啶）基] -3-丁烯-1-胺，（E ）-N-甲基-4-（5-嘧啶基）-3-丁烯-1-胺，（E）-N-甲基-4- [3-（5-甲氧基吡啶）基] -3-丁烯-1-胺 ，（Z） - 间苯胺，N-甲基 - （3-吡啶基） - 丁烷-1-胺，N-甲基-4-（3-吡啶基）-3-丁炔-1-胺和（E）-N-甲基 -4- [3-（6-甲基吡啶）基] -3-丁烯-1-胺。

公开(公告)号：US08476296B2

公开(公告)日：2013-07-02

申请号：US12740970

申请日：2010-01-25

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

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

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

CPC classification number: A61K31/444 ,  C07D453/02

Abstract: 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).

Abstract translation: 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：US20090068642A1

公开(公告)日：2009-03-12

申请号：US11387619

申请日：2006-03-23

Applicant: Merouane Bencherif ,  Ronald J. Lukas ,  Sharon Rae Letchworth ,  Vladimir Grinevich

Inventor： Merouane Bencherif ,  Ronald J. Lukas ,  Sharon Rae Letchworth ,  Vladimir Grinevich

IPC: C12Q1/68 ,  C12N5/08

CPC classification number: C07K14/70571

Abstract: Nicotinic acetylcholine receptors (nAChRs) comprising the α6 receptor subunit; nucleic acids, including vectors, comprising subunit incoding sequences; cells expressing the nAChRs of the invention; and methods of screening compounds are provided.

Abstract translation: 包含α6受体亚单位的烟碱乙酰胆碱受体（nAChR） 核酸，包括载体，其包含亚单位编码序列; 表达本发明的nAChR的细胞; 并提供了筛选化合物的方法。

公开(公告)号：US20090048290A1

公开(公告)日：2009-02-19

申请号：US12184312

申请日：2008-08-01

Applicant: Merouane Bencherif ,  Lisa Benson ,  Gary Maurice Dull ,  Nikolai Fedorov ,  Gregory J. Gatto ,  John Genus ,  Kristen G. Jordan ,  Jacob Mathew ,  Anatoly A. Mazurov ,  Lan Miao ,  Julio A. Munoz ,  Inigo Pfeiffer ,  Sondra Pfeiffer ,  Teresa Y. Phillips

Inventor： Merouane Bencherif ,  Lisa Benson ,  Gary Maurice Dull ,  Nikolai Fedorov ,  Gregory J. Gatto ,  John Genus ,  Kristen G. Jordan ,  Jacob Mathew ,  Anatoly A. Mazurov ,  Lan Miao ,  Julio A. Munoz ,  Inigo Pfeiffer ,  Sondra Pfeiffer ,  Teresa Y. Phillips

IPC: A61K31/439 ,  C07D453/02 ,  A61P25/00 ,  A61P29/00

CPC classification number: C07D453/02 ,  A61K31/439

Abstract: The present invention relates to (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide, novel salt forms thereof, methods for its preparation, novel intermediates, and methods for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central and autonomic nervous systems.

Abstract translation: 本发明涉及（2S，3R）-N-（2 - （（3-吡啶基）甲基）-1-氮杂双环[2.2.2]辛-3-基）苯并呋喃-2-甲酰胺，其新的盐形式， 其制备方法，新型中间体和用于治疗各种病症和障碍的方法，包括与中枢神经系统和自主神经系统的功能障碍相关的方法。

公开(公告)号：US06979695B2

公开(公告)日：2005-12-27

申请号：US10263083

申请日：2002-10-02

Applicant: William S. Caldwell ,  Gary M. Dull ,  Balwinder S. Bhatti ,  Srishailkumar B. Hadimani ,  Haeil Park ,  Jared M. Wagner ,  Peter A. Crooks ,  Patrick M. Lippiello ,  Merouane Bencherif

Inventor： William S. Caldwell ,  Gary M. Dull ,  Balwinder S. Bhatti ,  Srishailkumar B. Hadimani ,  Haeil Park ,  Jared M. Wagner ,  Peter A. Crooks ,  Patrick M. Lippiello ,  Merouane Bencherif

IPC: A61K31/44 ,  A61K31/505 ,  A61P25/28 ,  C07D213/38 ,  C07D213/61 ,  C07D213/65 ,  C07D213/73 ,  C07D239/26 ,  A61K31/4427

CPC classification number: C07D239/26 ,  A61K31/44 ,  A61K31/505 ,  C07D213/38 ,  C07D213/61 ,  C07D213/65 ,  C07D213/73 ,  C07D403/06

Abstract: The present invention generally relates to nicotinic compounds, in the form of aryl substituted olefinic compounds, as well as pro-drug, N-oxide, metabolite and pharmaceutically acceptable salt forms thereof. Methods of modulating neurotransmitter release via administration of the compounds, pro-drugs, N-oxides and/or pharmaceutically acceptable salts are also disclosed.

Abstract translation: 本发明一般涉及以芳基取代的烯属化合物形式的烟碱化合物，以及前药，N-氧化物，代谢产物和药学上可接受的盐形式。 还公开了通过施用化合物，前药，N-氧化物和/或药学上可接受的盐调节神经递质释放的方法。

公开(公告)号：US5731314A

公开(公告)日：1998-03-24

申请号：US364978

申请日：1995-01-06

Applicant: Merouane Bencherif ,  Patrick Michael Lippiello ,  William Scott Caldwell ,  Gary Maurice Dull

Inventor： Merouane Bencherif ,  Patrick Michael Lippiello ,  William Scott Caldwell ,  Gary Maurice Dull

IPC: A61K31/44 ,  A61K31/4406 ,  A61K31/505 ,  C07D213/65 ,  C07D239/26 ,  A61K31/435

CPC classification number: C07D239/26 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/505 ,  C07D213/65

Abstract: Patients susceptible to or suffering from Tourette's syndrome are treated by administering an effective amount of an aryl substituted aliphatic compound, an aryl substituted olefinic amine compound or an aryl substituted acetylenic compound. Exemplary compounds are (E)-4-(5-pyrimidinyl)-3-butene-1-amine, (E)-4-�3-(5-methoxypyridin)yl!-3-butene-1-amine, (E)-N-methyl-4-(5-pyrimidinyl)-3-butene-1-amine, (E)-N-methyl-4-�3-(5-methoxypyrindin)yl!-3-butene-1-amine, (Z)-metanicotine, (E)-metanicotine, N-methyl-(3-pyridinyl)-butane-1-amine, N-methyl-4-(3-pyridinyl)-3-butyne-1-amine and (E)-N-methyl-4-�3-(6-methylpyrindin)yl!-3-butene-1-amine.

Abstract translation: 通过施用有效量的芳基取代的脂肪族化合物，芳基取代的烯属胺化合物或芳基取代的炔属化合物来治疗易受感染或患有Tourette综合征的患者。 示例性化合物是（E）-4-（5-嘧啶基）-3-丁烯-1-胺，（E）-4- [3-（5-甲氧基吡啶）基] -3-丁烯-1-胺，（E ）-N-甲基-4-（5-嘧啶基）-3-丁烯-1-胺，（E）-N-甲基-4- [3-（5-甲氧基吡啶）基] -3-丁烯-1-胺 ，（Z） - 间苯胺，（E） - 间苯胺，N-甲基 - （3-吡啶基） - 丁烷-1-胺，N-甲基-4-（3-吡啶基）-3-丁炔-1-胺和（ E）-N-甲基-4- [3-（6-甲基嘧啶）基] -3-丁烯-1-胺。

公开(公告)号：US5510355A

公开(公告)日：1996-04-23

申请号：US301288

申请日：1994-09-06

Applicant: Merouane Bencherif ,  Patrick M. Lippiello ,  William S. Caldwell

Inventor： Merouane Bencherif ,  Patrick M. Lippiello ,  William S. Caldwell

IPC: C07D401/04 ,  A61K31/435 ,  A61K31/439 ,  A61K31/44 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/465 ,  A61P21/02 ,  C07D453/02

CPC classification number: A61K31/439 ,  A61K31/435 ,  A61K31/44 ,  A61K31/444 ,  A61K31/465

Abstract: Compounds such as 5-chloronicotine, 5-fluoronornicotine, anabaseine, 5-fluoroanabaseine, 2-acetoxymethylquinuclidine or!2-(3-pyridyl)-quinuclidine are useful as locally acting and highly selective muscle relaxants. Each compound, when administered intravenously, acts to bind to musculoskeletal nicotinic receptor sites in a reversible manner causing transient depolarization, and hence provides for reversible muscle relaxation to a patient during anesthesia.

Abstract translation: 化合物例如[5-氯烟碱，5-氟降烟碱，阿那霉素，5-氟尿嘧啶，2-乙酰氧基甲基奎宁环或2-（3-吡啶基） - 奎宁环可用作局部作用和高度选择性的肌肉松弛剂。 当静脉内施用时，每种化合物以可逆方式结合肌肉骨骼烟碱受体，引起瞬时去极化，因此在麻醉期间为患者提供可逆的肌肉松弛。