公开(公告)号：US08415347B2

公开(公告)日：2013-04-09

申请号：US12850958

申请日：2010-08-05

申请人： José Maria Cid-Núñez ,  Antonius Adrianus Hendrikus Petrus Megens ,  Andrés Avelino Trabanco-Suárez ,  Mohamed Koukni ,  Georges Joseph Cornelius Hoornaert ,  Frans Josef Cornelius Compernolle ,  Tomasz Kozlecki ,  Hua Mao ,  Sushil Chandra Jha ,  Francisco Javier Fernández-Gadea

发明人： José Maria Cid-Núñez ,  Antonius Adrianus Hendrikus Petrus Megens ,  Andrés Avelino Trabanco-Suárez ,  Mohamed Koukni ,  Georges Joseph Cornelius Hoornaert ,  Frans Josef Cornelius Compernolle ,  Tomasz Kozlecki ,  Hua Mao ,  Sushil Chandra Jha ,  Francisco Javier Fernández-Gadea

IPC分类号： A61K31/5377 ,  A61K31/403 ,  A61K31/496 ,  A61K31/381 ,  A61K31/4985 ,  A61K31/352 ,  A61K31/435 ,  C07D491/044 ,  C07D209/58 ,  C07D413/04 ,  C07D333/80 ,  C07D487/04

CPC分类号： C07D333/80 ,  C07D209/70 ,  C07D221/18 ,  C07D307/93 ,  C07D311/94 ,  C07D487/04 ,  C07D491/04

摘要： This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT2A and 5-HT2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production.The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

摘要翻译： 本发明涉及对5-羟色胺受体，特别是5-HT2A和5-HT2C受体以及对多巴胺受体，特别是多巴胺D2受体和去甲肾上腺素再摄取抑制性质具有结合亲和力的新型取代四环四氢呋喃，吡咯烷和四氢噻吩衍生物，包含 根据本发明的化合物，其用作药物，特别是用于预防和/或治疗一系列精神和神经障碍，特别是某些精神病性，心血管和胃肠功能障碍及其生产方法。 根据本发明的化合物可以由通式（I）表示，并且还包括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-氧化物形式及其前药，其中所有取代基定义为 在权利要求1中。

公开(公告)号：US07799785B2

公开(公告)日：2010-09-21

申请号：US11815726

申请日：2005-12-06

申请人： José Maria Cid-Núñez ,  Antonius Andrianus Hendrikus Petrus Megens ,  Andrés Avelino Trabanco-Suárez ,  Mohamed Koukni ,  Georges Joseph Cornelius Hoornaert ,  Frans Josef Cornelius Compernolle ,  Tomasz Kozlecki ,  Hua Mao ,  Sushil Chandra Jha ,  Francisco Javier Fernández-Gadea

发明人： José Maria Cid-Núñez ,  Antonius Andrianus Hendrikus Petrus Megens ,  Andrés Avelino Trabanco-Suárez ,  Mohamed Koukni ,  Georges Joseph Cornelius Hoornaert ,  Frans Josef Cornelius Compernolle ,  Tomasz Kozlecki ,  Hua Mao ,  Sushil Chandra Jha ,  Francisco Javier Fernández-Gadea

IPC分类号： A61K31/403 ,  A61K31/4985 ,  A61K31/352 ,  A61P3/04 ,  A61P25/00 ,  A61K31/381 ,  A61K31/407 ,  C07D487/04 ,  C07D209/56 ,  C07D491/044

CPC分类号： C07D333/80 ,  C07D209/70 ,  C07D221/18 ,  C07D307/93 ,  C07D311/94 ,  C07D487/04 ,  C07D491/04

摘要： This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT2A and 5-HT2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production.The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

摘要翻译： 本发明涉及对5-羟色胺受体，特别是5-HT2A和5-HT2C受体以及对多巴胺受体，特别是多巴胺D2受体和去甲肾上腺素再摄取抑制性质具有结合亲和力的新型取代四环四氢呋喃，吡咯烷和四氢噻吩衍生物，包含 根据本发明的化合物，其用作药物，特别是用于预防和/或治疗一系列精神和神经障碍，特别是某些精神病性，心血管和胃肠功能障碍及其生产方法。 根据本发明的化合物可以由通式（I）表示，并且还包括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-氧化物形式及其前药，其中所有取代基定义为 在权利要求1中。

公开(公告)号：US20080287450A1

公开(公告)日：2008-11-20

申请号：US11815726

申请日：2005-12-06

申请人： Jose Maria Cid-Nunez ,  Antonius Adrianus Hendrikus Petrus Megens ,  Andres Avelino Trabanco-Suarez ,  Mohamed Koukni ,  Georges Joseph Cornelius Hoornaert ,  Frans Josef Cornelius Compernolle ,  Tomasz Kozlecki ,  Hua Mao ,  Sushil Chandra Jha ,  Francisco Javier Fernandez-Gadea

发明人： Jose Maria Cid-Nunez ,  Antonius Adrianus Hendrikus Petrus Megens ,  Andres Avelino Trabanco-Suarez ,  Mohamed Koukni ,  Georges Joseph Cornelius Hoornaert ,  Frans Josef Cornelius Compernolle ,  Tomasz Kozlecki ,  Hua Mao ,  Sushil Chandra Jha ,  Francisco Javier Fernandez-Gadea

IPC分类号： A61K31/403 ,  C07D487/04 ,  C07D209/56 ,  C07D491/044 ,  A61K31/4985 ,  A61K31/352 ,  A61P3/04 ,  A61P25/00 ,  A61K31/381 ,  A61K31/407 ,  C07D333/50 ,  C07D311/94

CPC分类号： C07D333/80 ,  C07D209/70 ,  C07D221/18 ,  C07D307/93 ,  C07D311/94 ,  C07D487/04 ,  C07D491/04

摘要： This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT2A and 5-HT2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production.The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

摘要翻译： 本发明涉及对5-羟色胺受体，特别是5-HT 2A和5-HT 2C受体具有结合亲和力的新型取代四环四氢呋喃，吡咯烷和四氢噻吩衍生物，并且涉及多巴胺受体 ，特别是多巴胺D2受体和去甲肾上腺素再摄取抑制性质，包含根据本发明的化合物的药物组合物，其作为药物的用途，特别是用于预防和/或治疗一系列精神和神经障碍，特别是 某些精神病，心血管和胃肠功能障碍及其生产过程。 根据本发明的化合物可以由通式（I）表示，并且还包括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-氧化物形式及其前药，其中所有取代基定义为 在权利要求1中。

公开(公告)号：US20090023721A1

公开(公告)日：2009-01-22

申请号：US11915202

申请日：2006-05-24

申请人： Antonius Adrianus Hendrikus Petrus Megens ,  Andres Avelino Trabanco-Suarez ,  Jose Maria Cid-Nunez ,  Hua Mao ,  Sushil Chandra Jha ,  Francisco Javier Fernandez-Gadea ,  Mohamed Koukni ,  Georges Joseph Cornelius Hoornaert ,  Frans Josef Cornelius Compernolle ,  Tomasz Kozlecki

发明人： Antonius Adrianus Hendrikus Petrus Megens ,  Andres Avelino Trabanco-Suarez ,  Jose Maria Cid-Nunez ,  Hua Mao ,  Sushil Chandra Jha ,  Francisco Javier Fernandez-Gadea ,  Mohamed Koukni ,  Georges Joseph Cornelius Hoornaert ,  Frans Josef Cornelius Compernolle ,  Tomasz Kozlecki

IPC分类号： A61K31/4184 ,  C07D235/02 ,  C07D241/36 ,  C07D333/50 ,  A61K31/498 ,  A61K31/35 ,  A61K31/5377 ,  A61P25/00 ,  A61K31/403 ,  A61K31/381 ,  C07D311/02 ,  C07D209/56 ,  C07D413/12

CPC分类号： C07D209/94 ,  C07D221/18 ,  C07D307/93 ,  C07D311/94 ,  C07D333/80 ,  C07D487/04 ,  C07D491/04

摘要： This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT2A and 5-HT2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production.The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

摘要翻译： 本发明涉及对5-羟色胺受体，特别是5-HT2A和5-HT2C受体以及对多巴胺受体，特别是多巴胺D2受体和去甲肾上腺素再摄取抑制性质具有结合亲和力的新型取代四环四氢呋喃，吡咯烷和四氢噻吩衍生物，包含 根据本发明的化合物，其用作药物，特别是用于预防和/或治疗一系列精神和神经障碍，特别是某些精神病性，心血管和胃肠功能障碍及其生产方法。 根据本发明的化合物可以由通式（I）表示，并且还包括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-氧化物形式及其前药，其中所有取代基定义为 在权利要求1中。

公开(公告)号：US06998494B2

公开(公告)日：2006-02-14

申请号：US10496279

申请日：2002-12-02

申请人： Yolande Lydia Lang ,  Bart Petrus Anna Maria Jozef Medaer ,  Georges Joseph Cornelius Hoornaert ,  Thierry Brossette ,  Frans Josef Cornelius Compernolle ,  Michel Joseph Maurice André Guillaume ,  Hua Mao ,  Tomasz Kozlecki

发明人： Yolande Lydia Lang ,  Bart Petrus Anna Maria Jozef Medaer ,  Georges Joseph Cornelius Hoornaert ,  Thierry Brossette ,  Frans Josef Cornelius Compernolle ,  Michel Joseph Maurice André Guillaume ,  Hua Mao ,  Tomasz Kozlecki

IPC分类号： C07D307/93

CPC分类号： C07D307/93

摘要： The present invention concerns processes for the preparation of each of the 4 diastereomers of formula (I) in stereochemically pure form from either of two enantiomerically pure precursors. The tetracyclic ringsystem having trans-fused five and seven membered rings is formed in an acid-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates, the methanamine end-products, the methanamine end-products for use as a medicine, in particular as CNS active medicines.

摘要翻译： 本发明涉及制备式（I）的四种非对映异构体中的每一种的方法，化学式id =“CHEM-US-00001”num =“000

公开(公告)号：US20050228043A1

公开(公告)日：2005-10-13

申请号：US11141612

申请日：2005-05-31

申请人： Yolande Lang ,  Bart Petrus Anna Medaer ,  Georges Hoornaert ,  Thierry Brossette ,  Frans Compernolle ,  Michel Joseph Guillaume ,  Hua Mao ,  Tomasz Kozlecki

发明人： Yolande Lang ,  Bart Petrus Anna Medaer ,  Georges Hoornaert ,  Thierry Brossette ,  Frans Compernolle ,  Michel Joseph Guillaume ,  Hua Mao ,  Tomasz Kozlecki

IPC分类号： A61K31/34 ,  A61K31/343 ,  A61P25/06 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07D307/93

CPC分类号： C07D307/93

摘要： The present invention concerns processes for the preparation of each of the 4 diastereomers of formula (I) in stereochemically pure form from either of two enantiomerically pure precursors. The tetracyclic ringsystem having trans-fused five and seven membered rings is formed in an acid-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates, the methanamine end-products, the methanamine end-products for use as a medicine, in particular as CNS active medicines.

摘要翻译： 本发明涉及从两种对映异构体纯的前体中的任何一种以立体化学纯的形式制备式（I）的4种非对映异构体中的每一种的方法。 在酸催化的环化反应中形成具有反式稠合的五元和七元环的四环体系。 本发明还涉及由此获得的顺式稠合四环醇中间体，甲胺终产物，用作药物的甲胺最终产物，特别是CNS活性药物。

公开(公告)号：US20050014820A1

公开(公告)日：2005-01-20

申请号：US10496279

申请日：2002-12-02

申请人： Yolande Lang ,  Bart Petrus Medaer ,  George Hoornaert ,  Thierry Brossette ,  Frans Compernolle ,  Michel Joseph Guillaume ,  Hua Mao ,  Tomasz Kozlecki

发明人： Yolande Lang ,  Bart Petrus Medaer ,  George Hoornaert ,  Thierry Brossette ,  Frans Compernolle ,  Michel Joseph Guillaume ,  Hua Mao ,  Tomasz Kozlecki

IPC分类号： A61K31/34 ,  A61K31/343 ,  A61P25/06 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07D307/93 ,  C07D307/77

CPC分类号： C07D307/93

摘要： The present invention concerns processes for the preparation of each of the 4 diastereomers of formula (I) in stereochemically pure form from either of two enantiomerically pure precursors. The tetracyclic ringsystem having trans-fused five and seven membered rings is formed in an acid-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates, the methanamine end-products, the methanamine end-products for use as a medicine, in particular as CNS active medicines.

摘要翻译： 本发明涉及从两种对映异构体纯的前体中的任何一种以立体化学纯的形式制备式（I）的4种非对映异构体中的每一种的方法。 在酸催化的环化反应中形成具有反式稠合的五元和七元环的四环体系。 本发明还涉及由此获得的顺式稠合四环醇中间体，甲胺终产物，用作药物的甲胺最终产物，特别是CNS活性药物。

公开(公告)号：US09632098B2

公开(公告)日：2017-04-25

申请号：US13878230

申请日：2011-10-08

申请人： Xiaofeng Zeng ,  Yue Zhang ,  Zhinan Shou ,  Hua Mao ,  Hongbin Sun ,  Jie Qian ,  Yongjun Han ,  Weina Situ

发明人： Xiaofeng Zeng ,  Yue Zhang ,  Zhinan Shou ,  Hua Mao ,  Hongbin Sun ,  Jie Qian ,  Yongjun Han ,  Weina Situ

IPC分类号： G01N33/68 ,  C07K14/705 ,  C07K14/52 ,  C07K16/18 ,  G01N33/564 ,  A61K38/19

CPC分类号： G01N33/6893 ,  A61K38/19 ,  C07K14/52 ,  C07K14/705 ,  C07K16/18 ,  G01N33/564 ,  G01N33/6854 ,  G01N2800/52

摘要： The present application provides compositions and methods useful for detecting and monitoring autoimmune diseases in a human subject. The methods comprise providing a moesin fragment for binding to an anti-moesin autoantibody and contacting the moesin fragment with a sample obtained from the human subject. The moesin fragment comprises the entire N-terminal FERM domain of a human moesin protein. The human subject has or is suspected of having an autoimmune disease such as connective tissue disease, systemic sclerosis, Sjogren's syndrome, or systemic lupus erythematosus.

公开(公告)号：US09296774B2

公开(公告)日：2016-03-29

申请号：US13540609

申请日：2012-07-02

申请人： Hua Mao

发明人： Hua Mao

IPC分类号： A01N43/04 ,  A61K31/70 ,  A01N43/16 ,  A61K31/35 ,  C07H5/04 ,  C07H5/06 ,  C08B37/00 ,  C07H11/04 ,  C07H5/02 ,  C07D493/04

CPC分类号： C07H11/04 ,  C07D493/04 ,  C07H5/02

摘要： A halogenated dideoxy sugar derivative, having the following general structure I wherein X is halogen, R1 and R2 are H or Br; R3 and R4 are OH or OAc. The compounds 1-14 of the current invention has strong inhibition effect on human nasopharyngeal cancer CNE-2Z cells, human lung cancer A549 cells. human colon cancer HT-29 cells, human liver cancer Bel-7402 cells, human rectum cancer cells HCE 8693, human stomach cancer BGC-803 cells, human esophagus cancer CaEs-17 cells, human breast cancer cells MCF-7, human ovarian cancer cells A2780, pancreatic cancer cells PC-3, human bladder cells EJ, human brain glia cells TG-905, human leukemia cells K562, human melanoma M 14 cells and human anaplastic thyroid carcinoma TA-K cells. They can be used to prepare anti-tumor medicament and have significant clinic value.

摘要翻译： 具有以下一般结构I的卤代双脱氧糖衍生物，其中X是卤素，R 1和R 2是H或Br; R3和R4是OH或OAc。 本发明化合物1-14对人鼻咽癌CNE-2Z细胞，人肺癌A549细胞具有强烈的抑制作用。 人结肠癌HT-29细胞，人肝癌Bel-7402细胞，人直肠癌细胞HCE 8693，人胃癌BGC-803细胞，人食管癌CaEs-17细胞，人乳腺癌细胞MCF-7，人卵巢癌 细胞A2780，胰腺癌细胞PC-3，人膀胱细胞EJ，人脑胶质细胞TG-905，人白血病细胞K562，人黑素瘤M14细胞和人间变性甲状腺癌TA-K细胞。 它们可用于制备抗肿瘤药物，具有显着的临床价值。

公开(公告)号：US20130266537A1

公开(公告)日：2013-10-10

申请号：US13878232

申请日：2011-10-08

申请人： Yue Zhang ,  Jun Bao ,  Hua Mao ,  Zhinan Shou ,  Weina Situ

发明人： Yue Zhang ,  Jun Bao ,  Hua Mao ,  Zhinan Shou ,  Weina Situ

IPC分类号： C07K7/08 ,  A61K38/08 ,  A61K38/20 ,  A61K45/06 ,  A61K38/19 ,  C07K7/06 ,  A61K38/10

CPC分类号： A61K39/3955 ,  A61K38/08 ,  A61K38/10 ,  A61K38/191 ,  A61K38/2006 ,  A61K38/204 ,  A61K38/2086 ,  A61K45/06 ,  C07K7/06 ,  C07K7/08 ,  C07K16/18 ,  C07K16/28 ,  C07K2317/73 ,  C07K2317/76 ,  A61K2300/00

摘要： The present application provides compositions and methods useful for treating and diagnosing diseases and disorders associated with moesin activation.