公开(公告)号：US08754117B2

公开(公告)日：2014-06-17

申请号：US13752086

申请日：2013-01-28

Applicant: Sunovion Pharmaceuticals Inc.

Inventor： Liming Shao ,  Jianguo Ma

IPC: A61K31/4025 ,  A61K31/40 ,  C07D207/06 ,  C07D207/08 ,  C07D405/04

CPC classification number: C07D207/06 ,  A61K31/40 ,  C07D207/08 ,  C07D207/12 ,  C07D405/04

Abstract: In various embodiments, the present invention provides cycloalkyl pyrrolidine compounds and methods for their use in the treatment and/or prevention of various diseases, conditions and syndromes, including central nervous system (CNS) disorders, such as depression, anxiety, schizophrenia and sleep disorder as well as methods for their synthesis. The invention also relates to pharmaceutical compositions containing the compounds of the invention, as well as methods of inhibiting reuptake of endogenous monoamines, such as dopamine, serotonin and norepinephrine from the synaptic cleft and methods of modulating one or more monoamine transporter.

Abstract translation: 在各种实施方案中，本发明提供环烷基吡咯烷化合物及其用于治疗和/或预防各种疾病，病症和综合征的方法，包括中枢神经系统（CNS）障碍，例如抑郁症，焦虑症，精神分裂症和睡眠障碍 以及它们的合成方法。 本发明还涉及含有本发明化合物的药物组合物，以及抑制内源性单胺如从突触间隙中再摄取多巴胺，5-羟色胺和去甲肾上腺素以及调节一种或多种单胺转运蛋白的方法。

公开(公告)号：US20140121283A1

公开(公告)日：2014-05-01

申请号：US14139339

申请日：2013-12-23

Applicant: Sunovion Pharmaceuticals Inc.

Inventor： Thomas P. JERUSSI ,  Chrisantha H. SENANAYAKE ,  Nandkumar N. BHONGLE

IPC: A61K31/137

CPC classification number: C07C217/74 ,  A61K31/137 ,  A61K31/277 ,  C07B2200/07 ,  C07C213/00 ,  C07C213/02 ,  C07C215/64 ,  C07C2601/14

Abstract: Methods of preparing, and compositions comprising, derivatives of (−)-venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.

Abstract translation: 公开了制备方法和包含（ - ） - 文拉法辛的衍生物的组合物。 还公开了治疗和预防疾病和病症的方法，包括但不限于情感障碍如抑郁，双相和躁狂症，注意力缺陷障碍，具有多动症的注意缺陷障碍，帕金森病，癫痫，脑功能障碍，肥胖症和 体重增加，失禁，痴呆和相关疾病。

公开(公告)号：US08524950B2

公开(公告)日：2013-09-03

申请号：US13333616

申请日：2011-12-21

Applicant: Hang Zhao ,  Stefan G. Koenig ,  Charles P. Vandenbossche ,  Surendra Singh ,  Harold Scott Wilkinson ,  Roger P. Bakale

Inventor： Hang Zhao ,  Stefan G. Koenig ,  Charles P. Vandenbossche ,  Surendra Singh ,  Harold Scott Wilkinson ,  Roger P. Bakale

IPC: C07C321/00 ,  C07C323/00 ,  C07C381/00

CPC classification number: C07C231/14 ,  C07B43/06 ,  C07C209/50 ,  C07C209/62 ,  C07C211/42 ,  C07C231/12 ,  C07C249/08 ,  C07C2602/10

Abstract: This invention provides a convenient method for converting oximes into enamides. The process does not require the use of metallic reagents. Accordingly, it produces the desired compounds without the concomitant production of a large volume of metallic waste. The enamides are useful precursors to amides and amines. The invention provides a process to convert a prochiral enamide into the corresponding chiral amide. In an exemplary process, a chiral amino center is introduced during hydrogenation through the use of a chiral hydrogenation catalyst. In selected embodiments, the invention provides methods of preparing amides and amines that include the 1,2,3,4-tetrahydro-N-alkyl-1-naphthalenamine or 1,2,3,4-tetrahydro-1-naphthalenamine substructure.

Abstract translation: 本发明提供了将肟转化成烯酰胺的方便方法。 该方法不需要使用金属试剂。 因此，它产生所需化合物，而不伴随产生大量的金属废物。 酰胺是酰胺和胺的有用前体。 本发明提供了将前手性烯酰胺转化成相应的手性酰胺的方法。 在示例性方法中，通过使用手性氢化催化剂在氢化期间引入手性氨基中心。 在选择的实施方案中，本发明提供了制备包括1,2,3,4-四氢-N-烷基-1-萘胺或1,2,3,4-四氢-1-萘胺亚结构的酰胺和胺的方法。

公开(公告)号：US08497268B2

公开(公告)日：2013-07-30

申请号：US13483892

申请日：2012-05-30

Applicant: H. Scott Wilkinson ,  Richard Hsia ,  Tushar Misra ,  Kostas Saranteas ,  Patrick Mousaw

Inventor： H. Scott Wilkinson ,  Richard Hsia ,  Tushar Misra ,  Kostas Saranteas ,  Patrick Mousaw

IPC: A61K31/495

CPC classification number: C07D487/04 ,  C07C57/145

Abstract: Maleate salts of (6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine) are provided. The salts are useful to provide blood levels of eszopiclone that are independent of fasting state.

Abstract translation: （6-（5-氯-2-吡啶基）-5 - [（4-甲基-1-哌嗪基）羰氧基] -7-氧代-6,7-二氢-5H-吡咯并[3,4-b ]吡嗪）。 这些盐可用于提供独立于空腹状态的依佐替克的血液水平。

公开(公告)号：US08404670B2

公开(公告)日：2013-03-26

申请号：US13249166

申请日：2011-09-29

Applicant: Milan Chytil ,  Sharon R. Engel ,  Qun Kevin Fang ,  Kerry L. Spear

Inventor： Milan Chytil ,  Sharon R. Engel ,  Qun Kevin Fang ,  Kerry L. Spear

IPC: A61K31/33 ,  A61K31/55

CPC classification number: C07D487/04 ,  C07D471/14

Abstract: Provided herein are fused imidazolyl compounds, methods of synthesis, and methods of use thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders and metabolic disorders. Compounds provided herein inhibit the activity of histamine H3 receptors and modulate the release of various neurotransmitters, such as histamine, acetylcholine, norepinephrine, and dopamine (e.g. at the synapse). Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.

Abstract translation: 本文提供了稠合的咪唑基化合物，合成方法及其使用方法。 本文提供的化合物可用于治疗，预防和/或治疗各种疾病，例如神经障碍和代谢紊乱。 本文提供的化合物抑制组胺H3受体的活性并调节各种神经递质如组胺，乙酰胆碱，去甲肾上腺素和多巴胺（例如在突触）的释放。 本文还提供了含有化合物及其使用方法的药物制剂。

公开(公告)号：US08344030B2

公开(公告)日：2013-01-01

申请号：US13365565

申请日：2012-02-03

Applicant: Thomas Jerussi ,  Qun Kevin Fang ,  Mark G. Currie

Inventor： Thomas Jerussi ,  Qun Kevin Fang ,  Mark G. Currie

IPC: A61K31/135 ,  C07C211/42

CPC classification number: A61K31/135 ,  C07B2200/07 ,  C07C211/42 ,  C07C2602/10

Abstract: Treatment of CNS disorders with (1R,4S)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine; and (1S,4R)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine is disclosed. A process for preparing 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine is also disclosed. The process includes the preparation of all four isomers of N-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl]formamide, which are also useful.

公开(公告)号：US08173829B2

公开(公告)日：2012-05-08

申请号：US12751563

申请日：2010-03-31

Applicant: Craig R. Abolin ,  H. Scott Wilkinson ,  Paul McGlynn ,  William K. McVicar

Inventor： Craig R. Abolin ,  H. Scott Wilkinson ,  Paul McGlynn ,  William K. McVicar

IPC: C07C271/06

CPC classification number: C07C271/28 ,  C07B2200/07 ,  Y10T428/2982

Abstract: The compound of formula (I) is a water-stable, long acting β2-selective adrenoceptor agonist useful as a bronchodilator in the treatment of bronchoconstriction associated with reversible obstructive airways diseases and the like.

Abstract translation: 式（I）化合物是用作治疗与可逆性阻塞性气道疾病等相关的支气管收缩剂的支气管扩张剂的水稳定性长效β2-选择性肾上腺素受体激动剂。

公开(公告)号：US20120108670A1

公开(公告)日：2012-05-03

申请号：US13343118

申请日：2012-01-04

Applicant: Gerald J. TANOURY ,  Chris H. SENANAYAKE ,  Donald W. KESSLER

Inventor： Gerald J. TANOURY ,  Chris H. SENANAYAKE ,  Donald W. KESSLER

IPC: A61K31/137 ,  A61P11/08

CPC classification number: A61K31/205 ,  C07B2200/13 ,  C07C231/24 ,  C07C233/25 ,  C07C233/43

Abstract: A method of preparation of a highly pure salt of R,R-formoterol L-tartrate is disclosed. The process provides the most thermodynamically stable polymorph by recrystallization of a novel polymorph.

Abstract translation: 公开了制备R，R-福莫特醇L-酒石酸盐的高纯度盐的方法。 该方法通过重结晶新型多晶型物提供最热力学稳定的多晶型物。

公开(公告)号：US08097625B2

公开(公告)日：2012-01-17

申请号：US11761235

申请日：2007-06-11

Applicant: Karim Lalji ,  Timothy J. Barberich ,  Judy Caron ,  Thomas Wessel

Inventor： Karim Lalji ,  Timothy J. Barberich ,  Judy Caron ,  Thomas Wessel

IPC: A01N43/58 ,  A01N43/40 ,  A61K31/50 ,  A61K31/497 ,  A61K31/435

CPC classification number: A61K31/4985 ,  A61K31/137 ,  A61K31/138 ,  A61K31/495 ,  A61K31/724 ,  A61K45/06 ,  A61K2300/00

Abstract: One aspect of the present invention relates to pharmaceutical compositions containing two or more active agents that when taken together can be used to treat, e.g., insomnia and/or depression. The first component of the pharmaceutical composition is a GABA receptor modulating compound. The second component of the pharmaceutical composition is a serotonin reuptake inhibitor, a norepinephrine reuptake inhibitor, a 5-HT2A modulator, or dopamine reuptake inhibitor. In certain embodiments, the pharmaceutical composition comprises eszopiclone. In a preferred embodiment, the pharmaceutical composition comprises eszopiclone and fluoxetine. The present invention also relates to a method of treating a sleep abnormality, treating insomnia, treating depression, augmenting antidepressant therapy, eliciting a dose-sparing effect, reducing depression relapse, improving the efficacy of antidepressant therapy or improving the tolerability of antidepressant therapy, comprising co-administering to a patient in need thereof a GABA-receptor-modulating compound; and a SRI, NRI, 5-HT2A modulator or DRI.

Abstract translation: 本发明的一个方面涉及含有两种或更多种活性剂的药物组合物，当它们一起被用于治疗，例如失眠和/或抑郁症时。 药物组合物的第一组分是调节GABA受体的化合物。 药物组合物的第二组分是5-羟色胺再摄取抑制剂，去甲肾上腺素再摄取抑制剂，5-HT2A调节剂或多巴胺再摄取抑制剂。 在某些实施方案中，药物组合物包含依佐匹克。 在优选的实施方案中，药物组合物包含依佐匹克和氟西汀。 本发明还涉及一种治疗睡眠异常，治疗失眠，治疗抑郁症，增强抗抑郁药治疗，引发剂量保留作用，减少抑郁症复发，改善抗抑郁治疗疗效或提高抗抑郁治疗耐受性的方法，包括 向有需要的患者共同施用GABA受体调节化合物; 和SRI，NRI，5-HT2A调节剂或DRI。

公开(公告)号：US20110319380A1

公开(公告)日：2011-12-29

申请号：US12972293

申请日：2010-12-17

Applicant: Larry Wendell Hardy ,  Michele L. R. Heffernan ,  Frank Xinhe Wu ,  Kerry L. Spear ,  Lakshmi D. Saraswat

Inventor： Larry Wendell Hardy ,  Michele L. R. Heffernan ,  Frank Xinhe Wu ,  Kerry L. Spear ,  Lakshmi D. Saraswat

IPC: A61K31/517 ,  C07D417/10 ,  C07D413/04 ,  A61K31/5377 ,  A61P25/18 ,  C07D498/20 ,  C07D487/04 ,  A61P25/00 ,  A61P25/28 ,  C07D239/88 ,  C07D498/04

CPC classification number: C07D239/88 ,  C07D401/14 ,  C07D403/06 ,  C07D405/06 ,  C07D413/04 ,  C07D417/06 ,  C07D471/04 ,  C07D471/14 ,  C07D471/20 ,  C07D487/04 ,  C07D487/08 ,  C07D487/20 ,  C07D491/20 ,  C07D498/04

Abstract: Provided herein are compounds and methods of synthesis thereof. The compounds set forth herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders, neurodegenerative disorders, neuropsychiatric disorders, disorders of cognition, learning or memory, gastrointestinal disorders, lower urinary tract disorder, and cancer. Compounds set forth herein modulate the activity of metabotropic glutamate receptor 5 (mGluR5) in the central nervous system or the periphery. Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.

Abstract translation: 本文提供的化合物及其合成方法。 本文所述的化合物可用于治疗，预防和/或治疗各种疾病，例如神经障碍，神经变性疾病，神经精神障碍，认知障碍，学习或记忆障碍，胃肠道疾病，下尿路障碍和癌症 。 本文所述的化合物调节代谢型谷氨酸受体5（mGluR5）在中枢神经系统或周边的活性。 本文还提供了含有化合物及其使用方法的药物制剂。