公开(公告)号：US10351565B2

公开(公告)日：2019-07-16

申请号：US16005366

申请日：2018-06-11

申请人： JANSSEN PHARMACEUTICA NV

发明人： Bart DeCorte ,  Jacob Cornelis Russcher ,  Menno Cornelis Franciscus Monnee

IPC分类号： C07D471/18 ,  C07D451/04 ,  C07D451/12 ,  C07D451/00 ,  C07D451/06 ,  C07D451/10

摘要： The invention provides compounds of Formula 1: and stereoisomers, pharmaceutically acceptable salts and derivatives thereof; and methods of making and using such compounds. The invention includes pharmaceutical compositions containing such compounds, and the use of such compounds in methods of treating conditions, diseases, or disorders.

公开(公告)号：US20180327406A1

公开(公告)日：2018-11-15

申请号：US16043829

申请日：2018-07-24

申请人： JANSSEN PHARMACEUTICA NV

发明人： Bart DeCorte ,  Jacob Cornelis Russcher ,  Menno Cornelis Franciscus Monnee

IPC分类号： C07D471/18 ,  C07D451/00

CPC分类号： C07D471/18 ,  C07D451/00 ,  C07D451/04 ,  C07D451/06 ,  C07D451/10 ,  C07D451/12

摘要： The invention provides compounds of Formula 1: and stereoisomers, pharmaceutically acceptable salts and derivatives thereof; and methods of making and using such compounds. The invention includes pharmaceutical compositions containing such compounds, and the use of such compounds in methods of treating conditions, diseases, or disorders.

公开(公告)号：US20180009807A1

公开(公告)日：2018-01-11

申请号：US15544295

申请日：2016-01-25

申请人： Merck Sharp & Dohme Corp.

发明人： Reynalda K. deJesus ,  Qinghong Fu ,  Jinlong Jiang ,  Haifeng Tang

IPC分类号： C07D471/10 ,  C07D487/10 ,  C07D451/00 ,  A61K31/55 ,  A61K31/435 ,  A61K31/5386 ,  A61K31/46 ,  A61K31/444 ,  C07D498/10 ,  A61K45/06

摘要： The present invention provides compounds of Formula I (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

公开(公告)号：US09751881B2

公开(公告)日：2017-09-05

申请号：US14908222

申请日：2014-07-28

申请人： Merck Sharp & Dohme Corp.

发明人： Haifeng Tang ,  Barbara Pio ,  Jinlong Jiang ,  Alexander Pasternak ,  Shuzhi Dong ,  Ronald Dale Ferguson, II ,  Zack Zhiqiang Guo ,  Harry Chobanian ,  Jessica Frie ,  Yan Guo ,  Zhicai Wu ,  Yang Yu ,  Ming Wang

IPC分类号： C07D471/10 ,  C07D451/00 ,  C07D493/04 ,  C07D498/10 ,  A61K31/435 ,  A61K31/444 ,  A61K31/46 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5386 ,  A61K45/06

CPC分类号： C07D471/10 ,  A61K31/435 ,  A61K31/444 ,  A61K31/46 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5386 ,  A61K45/06 ,  C07D451/00 ,  C07D493/04 ,  C07D498/10

摘要： The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

公开(公告)号：US09550782B2

公开(公告)日：2017-01-24

申请号：US13789376

申请日：2013-03-07

申请人： Medivation Technologies, Inc.

发明人： Andrew Asher Protter ,  Sarvajit Chakravarty ,  Rajendra Parasmal Jain ,  Michael John Green

IPC分类号： A61K31/55 ,  A61K31/444 ,  C07D487/04 ,  A61K45/06 ,  C07D471/04 ,  C07D471/14 ,  C07D471/18 ,  C07D471/22 ,  C07D451/00 ,  C07D455/03

CPC分类号： C07D487/04 ,  A61K31/444 ,  A61K31/55 ,  A61K45/06 ,  C07D451/00 ,  C07D455/03 ,  C07D471/04 ,  C07D471/14 ,  C07D471/18 ,  C07D471/22

摘要： Hydrogenated pyrido[4,3-b]indoles, pyrido[3,4-b]indoles and azepino[4,5-b]indoles are described. The compounds may bind to and are antagonists of the adrenergic receptor α2A. The compounds may also bind to and are an antagonist of the adrenergic receptor α2B; or the compounds are not antagonists of the adrenergic receptor α2B and the compounds are administered in conjunction with a second agent that reduces, or is expected to reduce, blood pressure in an individual. The compounds may find use in therapy, e.g., to regulate blood glucose level, increase insulin secretion and treat diseases or conditions that are, or are expected to be, responsive to an increase in insulin production. Use of the compounds to treat type 2 diabetes is particularly described.

摘要翻译： 描述了氢化吡啶并[4,3-b]吲哚，吡啶并[3,4-b]吲哚和氮杂环[4,5-b]吲哚。 该化合物可以结合肾上腺素能受体α2A并且是拮抗剂。 该化合物还可以结合并且是肾上腺素能受体α2B的拮抗剂; 或者化合物不是肾上腺素能受体α2B的拮抗剂，并且化合物与减少或预期降低个体血压的第二药剂一起施用。 该化合物可用于治疗，例如调节血糖水平，增加胰岛素分泌并治疗对胰岛素产生增加或预期是响应的疾病或病症。 特别描述了化合物治疗2型糖尿病的用途。

公开(公告)号：US09242979B2

公开(公告)日：2016-01-26

申请号：US14605618

申请日：2015-01-26

申请人： Mahmut Bilgic

发明人： Mahmut Bilgic

IPC分类号： C07D491/08 ,  A61K31/44 ,  C07D451/00 ,  C07D333/24 ,  C07D491/18

CPC分类号： C07D333/24 ,  C07D409/14 ,  C07D451/00 ,  C07D491/18

摘要： The present invention relates to methods for synthesizing tiotropium bromide following the scheme: Using the above scheme, tiotropium bromide (compound 6C) is obtained under mild conditions and with high yields.

摘要翻译： 本发明涉及以下方案合成噻托溴铵的方法：使用上述方案，在温和条件下以高收率获得噻托溴铵（化合物6C）。

公开(公告)号：US09051314B2

公开(公告)日：2015-06-09

申请号：US14033234

申请日：2013-09-20

申请人： Medivation Technologies, Inc.

发明人： David T. Hung ,  Andrew Asher Protter ,  Sarvajit Chakravarty ,  Rajendra Parasmal Jain

IPC分类号： A61K31/54 ,  C07D451/00 ,  C07D471/18 ,  C07D471/08

CPC分类号： C07D451/00 ,  C07D471/08 ,  C07D471/18

摘要： This disclosure relates to new compounds that may be used to modulate a histamine receptor in an individual. Novel compounds are described, including new bridged heterocyclic [4,3-b]indole compounds. Pharmaceutical compositions are also provided. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

公开(公告)号：US20150148540A1

公开(公告)日：2015-05-28

申请号：US14605618

申请日：2015-01-26

申请人： Mahmut BILGIC

发明人： Mahmut BILGIC

IPC分类号： C07D451/00

CPC分类号： C07D333/24 ,  C07D409/14 ,  C07D451/00 ,  C07D491/18

摘要： Present invention relates to methods for preparing (1α,2β,4β,5α,7β)-7-[(hydroxidi-2-thienllacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane-bromide.

摘要翻译： 本发明涉及制备（1α，2α，bgr，4α，bα，7α，7α）-7 - [（羟基-2-噻吩并乙酰基）氧基] -9,9-二甲基-3-氧杂-9-氮杂三环[3.3 .1.02,4]壬烷溴化物。

公开(公告)号：US09000005B2

公开(公告)日：2015-04-07

申请号：US13788271

申请日：2013-03-07

申请人： ArQule, Inc.

发明人： Yoshitaka Nakamura ,  Jo Ooyama

IPC分类号： C07D471/06 ,  C07D451/00 ,  C07D453/00 ,  C07D455/00 ,  A61K31/473

CPC分类号： C07D471/06

摘要： The present invention relates to highly-pure pyrroloquinolinyl-pyrrole-2,5-dione and pyrroloquinolinyl-pyrrolidine-2,5-dione, for example, 3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione, 3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione, and pharmaceutically acceptable salts, solvates, and diastereomers thereof. The present invention also relates to methods for preparing highly-pure pyrroloquinolinyl-pyrrole-2,5-dione and pyrroloquinolinyl-pyrrolidine-2,5-dione, for example, 3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione, 3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione, and pharmaceutically acceptable salts, solvates, and diastereomers thereof.

摘要翻译： 本发明涉及高纯度的吡咯并喹啉基 - 吡咯-2,5-二酮和吡咯并喹啉基 - 吡咯烷-2,5-二酮，例如3-（5,6-二氢-4H-吡咯并[3,2,1- ij]喹啉-1-基）-4-（1H-吲哚-3-基）-1H-吡咯-2,5-二酮，3-（5,6-二氢-4H-吡咯并[3,2,1- ij]喹啉-1-基）-4-（1H-吲哚-3-基）吡咯烷-2,5-二酮及其药学上可接受的盐，溶剂化物和非对映异构体。 本发明还涉及制备高纯度的吡咯并喹啉基 - 吡咯-2,5-二酮和吡咯并喹啉基 - 吡咯烷-2,5-二酮的方法，例如3-（5,6-二氢-4H-吡咯并[ 2,1-ij]喹啉-1-基）-4-（1H-吲哚-3-基）-1H-吡咯-2,5-二酮，3-（5,6-二氢-4H-吡咯并[ 2,1-ij]喹啉-1-基）-4-（1H-吲哚-3-基）吡咯烷-2,5-二酮及其药学上可接受的盐，溶剂化物和非对映异构体。

公开(公告)号：US08969402B2

公开(公告)日：2015-03-03

申请号：US13778530

申请日：2013-02-27

申请人： Steven A. Rich

发明人： Steven A. Rich

IPC分类号： A01N43/36 ,  A61K31/40 ,  A01N43/40 ,  A61K31/445 ,  A01N47/10 ,  A61K31/27 ,  C07D207/00 ,  A61K31/137 ,  A61K31/216 ,  C07D207/12 ,  C07D451/00 ,  A61K31/435 ,  A61K31/4015 ,  A61K31/438 ,  A61K31/165 ,  A61K31/407

CPC分类号： A61K31/40 ,  A61K9/0014 ,  A61K9/0053 ,  A61K9/7023 ,  A61K31/137 ,  A61K31/165 ,  A61K31/20 ,  A61K31/201 ,  A61K31/202 ,  A61K31/216 ,  A61K31/27 ,  A61K31/4015 ,  A61K31/407 ,  A61K31/435 ,  A61K31/438 ,  A61K31/439 ,  A61K31/445 ,  C07D207/12 ,  C07D451/00

摘要： A method administers quaternary ammonium anti-cholinergic muscarinic receptor antagonists in combination with acetyl-cholinesterase inhibitors to treat either cognitive impairment or acute delirium. This therapy results in a modification of a cognitive disorder or disease, namely a slow down in the disease progression. In one preferred embodiment, the disease is dementia with Lewy Bodies. New formulations for quaternary ammonium anti-cholinergic muscarinic receptor antagonists are also disclosed.