公开(公告)号：US20150284351A1

公开(公告)日：2015-10-08

申请号：US14434563

申请日：2013-10-10

申请人： TOPHARMAN SHANGHAI CO., LTD. ,  SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES ,  TOPHARMAN SHANDONG CO., LTD.

发明人： Guan Wang ,  Xiangrui Jiang ,  Xudong Gong ,  Weiming Chen ,  Fuqiang Zhu ,  Rongxia Zhang ,  Xianguo Zhao

IPC分类号： C07D307/33 ,  C07D413/12

CPC分类号： C07D307/33 ,  C07D413/12

摘要： This invention disclose (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone in a single configuration and preparation method and use thereof. The (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone, or a pharmaceutically acceptable salt, an ester, a prodrug or a solvate thereof according to the invention are important intermediates of a variety of anti-viral and anti-tumor active ingredients. A compound obtained from (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone via an acylation reaction can be directly used for preparing various anti-viral and anti-tumor drugs. The Chiral synthesis method and the spontaneous resolution method of the compound of (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone according to the invention have the following advantages: the reaction routes are short and simple with high yield and low cost, which are suitable for industrial application.

摘要翻译： 本发明公开了单一构型的（2R）-2-脱氧-2,2-二取代 - 内酰基-1,4-内酯及其制备方法和用途。 根据本发明的（2R）-2-脱氧-2,2-二取代 - 内酰基-1,4-内酯或其药学上可接受的盐，酯，前药或溶剂化物是各种抗 - 病毒和抗肿瘤活性成分。 通过酰化反应从（2R）-2-脱氧-2,2-二取代 - 内酰基-1,4-内酯获得的化合物可以直接用于制备各种抗病毒和抗肿瘤药物。 根据本发明的（2R）-2-脱氧-2,2-二取代 - 内酰基-1,4-内酯化合物的手性合成方法和自发拆分方法具有以下优点：反应路线短而简单 产量高，成本低，适合工业应用。

公开(公告)号：US09376410B2

公开(公告)日：2016-06-28

申请号：US14434563

申请日：2013-10-10

申请人： TOPHARMAN SHANGHAI CO., LTD. ,  SHANGHAI INSTITUTE OF MATERIA MEDICA , CHINESE ACADEMY OF SCIENCES ,  TOPHARMAN SHANDONG CO., LTD.

发明人： Guan Wang ,  Xiangrui Jiang ,  Xudong Gong ,  Weiming Chen ,  Fuqiang Zhu ,  Rongxia Zhang ,  Xianguo Zhao

IPC分类号： C07D307/00 ,  C07D307/33 ,  C07D413/12

CPC分类号： C07D307/33 ,  C07D413/12

摘要： This invention disclose (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone in a single configuration and preparation method and use thereof. The (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone, or a pharmaceutically acceptable salt, an ester, a prodrug or a solvate thereof according to the invention are important intermediates of a variety of anti-viral and anti-tumor active ingredients. A compound obtained from (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone via an acylation reaction can be directly used for preparing various anti-viral and anti-tumor drugs. The Chiral synthesis method and the spontaneous resolution method of the compound of (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone according to the invention have the following advantages: the reaction routes are short and simple with high yield and low cost, which are suitable for industrial application.

摘要翻译： 本发明公开了单一构型的（2R）-2-脱氧-2,2-二取代 - 内酰基-1,4-内酯及其制备方法和用途。 根据本发明的（2R）-2-脱氧-2,2-二取代 - 内酰基-1,4-内酯或其药学上可接受的盐，酯，前药或溶剂化物是各种抗 - 病毒和抗肿瘤活性成分。 通过酰化反应从（2R）-2-脱氧-2,2-二取代 - 内酰基-1,4-内酯获得的化合物可以直接用于制备各种抗病毒和抗肿瘤药物。 根据本发明的（2R）-2-脱氧-2,2-二取代 - 内酰基-1,4-内酯化合物的手性合成方法和自发拆分方法具有以下优点：反应路线短而简单 产量高，成本低，适合工业应用。

公开(公告)号：US10174011B2

公开(公告)日：2019-01-08

申请号：US15124264

申请日：2015-03-09

申请人： SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES ,  SUZHOU VIGONVITA LIFE SCIENCES CO., LTD. ,  TOPHARMAN SHANDONG CO., LTD.

发明人： Hualiang Jiang ,  Zhen Wang ,  Jianfeng Li ,  Rongxia Zhang ,  Yang He ,  Yongjian Liu ,  Minghao Bi ,  Zheng Liu ,  Guanghui Tian ,  Weiming Chen ,  Feipu Yang ,  Chunhui Wu ,  Yu Wang ,  Xiangrui Jiang ,  Jingjing Yin ,  Guan Wang ,  Jingshan Shen

IPC分类号： C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D495/04 ,  C07D519/00 ,  A61K31/496 ,  A61K31/519 ,  A61K31/4709 ,  A61K31/517 ,  A61K31/538 ,  A61K31/5415 ,  A61K31/55

摘要： The present invention provides a heterocyclic compound represented by the formula (I), its stereoisomers, or a pharmaceutically acceptable salt thereof, pharmaceutical compositions thereof, and their use in preparing a medicament for the prevention and/or treatment of central nervous system disease.

公开(公告)号：US11384073B2

公开(公告)日：2022-07-12

申请号：US17127350

申请日：2020-12-18

申请人： SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES ,  SUZHOU VIGONVITA LIFE SCIENCES CO., LTD. ,  TOPHARMAN SHANGHAI CO., LTD.

发明人： Jingshan Shen ,  Yang He ,  Zhen Wang ,  Jianfeng Li ,  Yongjian Liu ,  Jin Suo ,  Guanghui Tian ,  Weiming Chen ,  Feipu Yang ,  Yu Wang ,  Xiangrui Jiang ,  Rongxia Zhang ,  Hualiang Jiang

IPC分类号： C07D409/12

摘要： The present disclosure relates to a maleate salt of a benzothiophene compound, a crystalline form thereof, and a use thereof. Specifically, the present disclosure relates to a compound represented by formula (I-A), a crystalline form A thereof, a preparation method of a pharmaceutical composition including the same, and a use of the pharmaceutical composition in the preparation of drugs for preventing or treating diseases of the central nervous system. The compound represented by formula (I-A) and the crystalline form A thereof in the present disclosure have excellent physical and chemical properties, high oral bioavailability, excellent drugability, and are well-suited for pharmaceutical preparation, application, and preservation.

公开(公告)号：US10100044B2

公开(公告)日：2018-10-16

申请号：US15030331

申请日：2014-10-20

申请人： SUZHOU VIGONVITA LIFE SCIENCES CO., LTD. ,  TOPHARMAN SHANGHAI CO., LTD. ,  SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

发明人： Zheng Liu ,  Chunhui Wu ,  Yongjian Liu ,  Rongxia Zhang ,  Yang He ,  Guanghui Tian ,  Jingshan Shen

IPC分类号： C07D333/70 ,  C07D409/12 ,  C07D333/54

摘要： The present invention relates to the methods for preparing brexpiprazole, the analogs, key intermediates, and salts thereof, specifically, the present invention relates to a new method for preparing brexpiprazole, the analogs, key intermediates, and salts thereof, and the key intermediates, and salts thereof provided during the preparation. The preparation method has a mild reaction condition, stable intermediate, easy operation, and uses cheap and easy-to-get reagents, thus it saves the synthesis cost, shortens the production cycle, improves the yield and product quality, and is suitable for mass production.

公开(公告)号：US20210309648A1

公开(公告)日：2021-10-07

申请号：US17127350

申请日：2020-12-18

申请人： SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES ,  SUZHOU VIGONVITA LIFE SCIENCES CO., LTD. ,  TOPHARMAN SHANGHAI CO., LTD.

发明人： Jingshan Shen ,  Yang He ,  Zhen Wang ,  Jianfeng Li ,  Yongjian Liu ,  Jin Suo ,  Guanghui Tian ,  Weiming Chen ,  Feipu Yang ,  Yu Wang ,  Xiangrui Jiang ,  Rongxia Zhang ,  Hualiang Jiang

IPC分类号： C07D409/12

摘要： The present disclosure relates to a maleate salt of a benzothiophene compound, a crystalline form thereof, and a use thereof. Specifically, the present disclosure relates to a compound represented by formula (I-A), a crystalline form A thereof, a preparation method of a pharmaceutical composition including the same, and a use of the pharmaceutical composition in the preparation of drugs for preventing or treating diseases of the central nervous system. The compound represented by formula (I-A) and the crystalline form A thereof in the present disclosure have excellent physical and chemical properties, high oral bioavailability, excellent drugability, and are well-suited for pharmaceutical preparation, application, and preservation.

公开(公告)号：US20140046074A1

公开(公告)日：2014-02-13

申请号：US13982733

申请日：2012-01-31

申请人： SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES ,  TOPHARMAN SHANGHAI CO., LTD.

发明人： Qiang Zhang ,  Rongxia Zhang ,  Guanghui Tian ,  Jianfeng Li ,  Fuqiang Zhu ,  Xiangrui Jiang ,  Jingshan Shen

IPC分类号： C07C213/02 ,  C07C59/64 ,  C07C235/34 ,  C07C309/75 ,  C07C309/66 ,  C07C43/225 ,  C07C215/54 ,  C07D263/26 ,  C07C43/23

CPC分类号： C07C235/34 ,  C07C17/16 ,  C07C41/26 ,  C07C43/225 ,  C07C43/23 ,  C07C59/64 ,  C07C59/68 ,  C07C213/02 ,  C07C215/54 ,  C07C217/62 ,  C07C309/66 ,  C07C309/73 ,  C07C309/75 ,  C07D263/26 ,  C07D263/52 ,  Y02P20/582 ,  C07C22/04

摘要： The present invention relates to a (2R, 3R)-3-(3-substituted phenyl)-2-methyl n-pentanamide compounds as shown in the formula I and the preparation method thereof, wherein, the substituents are as defined in the specification, the present invention further relates to a use of the above compounds for the preparation of tapentadol II or its pharmaceutically acceptable salt, and the intermediates involved in the preparation process.

摘要翻译： 本发明涉及式I所示的（2R，3R）-3-（3-取代苯基）-2-甲基正戊酰胺化合物及其制备方法，其中取代基如本说明书中所定义 ，本发明还涉及上述化合物在制备他喷他多II或其药学上可接受的盐中的用途，以及参与制备方法的中间体。

公开(公告)号：US11434226B2

公开(公告)日：2022-09-06

申请号：US16736300

申请日：2020-01-07

申请人： SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES ,  SUZHOU VIGONVITA LIFE SCIENCES CO., LTD. ,  TOPHARMAN SHANGHAI CO., LTD.

发明人： Jingshan Shen ,  Yang He ,  Weiming Chen ,  Jianfeng Li ,  Guanghui Tian ,  Xudong Gong ,  Zhen Wang ,  Rongxia Zhang ,  Yongjian Liu ,  Hualiang Jiang

IPC分类号： C07D403/12 ,  A61K45/06

摘要： The present disclosure relates to a salt of phenyl pyrimidinone compound, a polymorph thereof and a pharmaceutical composition comprising the same and a use thereof, particularly relates to the hydrochlorate of phenyl pyrimidinone compound of following formula (I-A) and a pharmaceutically acceptable polymorph, solvate, hydrate, co-crystal, anhydrous substance, or amorphous form thereof, a pharmaceutical composition and a pharmaceutical unit dosage comprising the same, the preparing method and use thereof.