公开(公告)号：US20120083483A1

公开(公告)日：2012-04-05

申请号：US13260684

申请日：2010-03-25

申请人： Craig A. Coburn ,  John A. McCauley ,  Steven W. Ludmerer ,  Kun Liu ,  Joseph P. Vacca ,  Hao Wu ,  Bin Hu ,  Richard Soll ,  Fei Sun ,  Xinghai Wang ,  Man Yan ,  Chengren Zhang ,  Mingwei Zheng ,  Bin Zhong ,  Jian Zhu

发明人： Craig A. Coburn ,  John A. McCauley ,  Steven W. Ludmerer ,  Kun Liu ,  Joseph P. Vacca ,  Hao Wu ,  Bin Hu ,  Richard Soll ,  Fei Sun ,  Xinghai Wang ,  Man Yan ,  Chengren Zhang ,  Mingwei Zheng ,  Bin Zhong ,  Jian Zhu

IPC分类号： A61K31/553

CPC分类号： C07D498/04 ,  A61K31/4025 ,  A61K31/404 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5365 ,  A61K31/5377 ,  A61K31/5383 ,  A61K31/553 ,  A61K38/05 ,  A61K38/06 ,  A61K45/06 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D487/04 ,  C07D498/10 ,  C07K5/06 ,  C07K5/08

摘要： The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5A inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5A activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

摘要翻译： 本发明涉及可用作丙型肝炎病毒（HCV）NS5A抑制剂，这种化合物的合成以及这些化合物用于抑制HCV NS5A活性用于治疗或预防HCV感染的用途的式（I）化合物和 抑制基于细胞的系统中的HCV病毒复制和/或病毒生产。

公开(公告)号：US08871759B2

公开(公告)日：2014-10-28

申请号：US13260684

申请日：2010-03-25

申请人： Craig A. Coburn ,  Steven W. Ludmerer ,  Kun Liu ,  Hao Wu ,  Richard Soll ,  Bin Zhong ,  Jian Zhu

发明人： Craig A. Coburn ,  Steven W. Ludmerer ,  Kun Liu ,  Hao Wu ,  Richard Soll ,  Bin Zhong ,  Jian Zhu

IPC分类号： A61K31/5365 ,  C07D413/14

CPC分类号： C07D498/04 ,  A61K31/4025 ,  A61K31/404 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5365 ,  A61K31/5377 ,  A61K31/5383 ,  A61K31/553 ,  A61K38/05 ,  A61K38/06 ,  A61K45/06 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D487/04 ,  C07D498/10 ,  C07K5/06 ,  C07K5/08

摘要： The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5A inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5A activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

摘要翻译： 本发明涉及可用作丙型肝炎病毒（HCV）NS5A抑制剂，这种化合物的合成以及这些化合物用于抑制HCV NS5A活性用于治疗或预防HCV感染的用途的式（I）化合物和 抑制基于细胞的系统中的HCV病毒复制和/或病毒生产。

公开(公告)号：US20140199264A1

公开(公告)日：2014-07-17

申请号：US14005430

申请日：2012-03-16

申请人： Craig A. Coburn ,  Stuart B. Rosenblum ,  Joseph A. Kozlowski ,  Richard Soll ,  Hao Wu ,  Bin Hu ,  Bin Zhong ,  Dahai Wang ,  Changmao Shen ,  Fei Sun

发明人： Craig A. Coburn ,  Stuart B. Rosenblum ,  Joseph A. Kozlowski ,  Richard Soll ,  Hao Wu ,  Bin Hu ,  Bin Zhong ,  Dahai Wang ,  Changmao Shen ,  Fei Sun

IPC分类号： A61K31/5383 ,  A61K45/06 ,  A61K31/4178 ,  C07D498/06 ,  C07D493/06

CPC分类号： A61K31/5383 ,  A61K31/4178 ,  A61K45/06 ,  C07D491/06 ,  C07D493/06 ,  C07D498/06

摘要： The present invention relates to novel Tetracyclic Xanthene Derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, Y1, Y2, Z, Ra, Rb, R1a, R1b and R2 are as defined herein. The present invention also relates to compositions comprising at least one Tetracyclic Xanthene Derivative, and methods of using the Tetracyclic Xanthene Derivatives for treating or preventing HCV infection in a patient.

摘要翻译： 本发明涉及式（I）的新型四环Xanthene衍生物及其药学上可接受的盐，其中A，Y1，Y2，Z，Ra，Rb，R1a，R1b和R2如本文所定义。 本发明还涉及包含至少一种四环Xanthene衍生物的组合物，以及使用四环Xanthene衍生物治疗或预防患者HCV感染的方法。

公开(公告)号：US09504690B2

公开(公告)日：2016-11-29

申请号：US14005430

申请日：2012-03-16

申请人： Craig A. Coburn ,  Stuart B. Rosenblum ,  Joseph A. Kozlowski ,  Richard Soll ,  Hao Wu ,  Bin Hu ,  Bin Zhong ,  Dahai Wang ,  Changmao Shen ,  Fei Sun

发明人： Craig A. Coburn ,  Stuart B. Rosenblum ,  Joseph A. Kozlowski ,  Richard Soll ,  Hao Wu ,  Bin Hu ,  Bin Zhong ,  Dahai Wang ,  Changmao Shen ,  Fei Sun

IPC分类号： A61K31/535 ,  A61K31/5383 ,  C07D491/06 ,  C07D498/06 ,  A61K31/4178 ,  A61K45/06 ,  C07D493/06

CPC分类号： A61K31/5383 ,  A61K31/4178 ,  A61K45/06 ,  C07D491/06 ,  C07D493/06 ,  C07D498/06

摘要： The present invention relates to novel Tetracyclic Xanthene Derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, Y1, Y2, Z, Ra, Rb, R1a, R1b and R2 are as defined herein. The present invention also relates to compositions comprising at least one Tetracyclic Xanthene Derivative, and methods of using the Tetracyclic Xanthene Derivatives for treating or preventing HCV infection in a patient.

公开(公告)号：US20190175602A1

公开(公告)日：2019-06-13

申请号：US16326039

申请日：2017-08-14

申请人： Wensheng Yu ,  LING Tong ,  Joseph A. Koziowski ,  Craig: A Coburn ,  De-yi J. Yang ,  Deyou Sha ,  Jae-Hun. Kim ,  Michael Dwyer ,  Kartik M. Keertikar ,  Bin Hu ,  Bin Zhong ,  Jinglai Hao ,  Dahai Wang

发明人： Wensheng Yu ,  LING Tong ,  Joseph A. Koziowski ,  Craig: A Coburn ,  De-yi J. Yang ,  Deyou Sha ,  Jae-Hun. Kim ,  Michael Dwyer ,  Kartik M. Keertikar ,  Bin Hu ,  Bin Zhong ,  Jinglai Hao ,  Dahai Wang

IPC分类号： A61K31/5365 ,  C07D498/04 ,  A61P31/14 ,  A61K31/4995 ,  C07D519/00

摘要： The present invention relates to novel Heterocycle-Substituted Tetracyclic Compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, A′, R2 R3 and R5 are as defined herein. The present invention also relates to compositions comprising at least one Heterocycle-Substituted Tetra-cyclic Compound, and methods of using the Heterocycle-Substituted Tetracyclic Compounds for treating or preventing HCV infection in a patient.

公开(公告)号：US20170073354A1

公开(公告)日：2017-03-16

申请号：US15124635

申请日：2015-03-06

申请人： Jurgen SCHULZ ,  Peter D. WILLIAMS ,  John A. MCCAULEY ,  Christopher J. BUNGARD ,  David Jonathan BENNETT ,  Sherman T. WADDELL ,  Gregori J. MORRIELLO ,  Lehua CHANG ,  Michael P. DWYER ,  Katharine M. HOLLOWAY ,  Alejandro CRESPO ,  Xin-Jie CHU ,  Catherine WISCOUNT ,  Marie H. LOUGHRAN ,  Jesse J. MANIKOWSKI ,  Kartik M. KEERTIKAR ,  Bin HU ,  Bin ZHONG ,  Tao JI ,  Merck Sharp & Dohme Corp. ,  MSD R&D (China) Co., Ltd.

发明人： Peter D. Williams ,  John A. McCauley ,  Christopher J. Bungard ,  David Jonathan Bennett ,  Sherman T. Waddell ,  Gregori J. Morriello ,  Lehua Chang ,  Michael P. Dwyer ,  M. Katharine Holloway ,  Alejandro Crespo ,  Xin-Jie Chu ,  Catherine Wiscount ,  H. Marie Loughran ,  Jesse J. Manikowski ,  Jurgen Schulz ,  Kartik M. Keertikar ,  Bin Hu ,  Bin Zhong ,  Tao Ji

IPC分类号： C07D513/08 ,  A61K31/554 ,  A61K45/06

CPC分类号： C07D513/08 ,  A61K31/554 ,  A61K45/06

摘要： The present invention is directed to compounds of Formula I pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.

摘要翻译： 本发明涉及含有该化合物的式I药物组合物的化合物及其在抑制HIV蛋白酶，抑制HIV复制，预防HIV感染，HIV感染治疗和预防， 治疗和延迟艾滋病的发病或进展。

公开(公告)号：US20190185486A1

公开(公告)日：2019-06-20

申请号：US16326043

申请日：2017-08-14

申请人： Wensheng Yu ,  Joseph A. Kozlowski ,  Ling Tong ,  Craig A. Cobum ,  Bin Hu ,  Bin Zhong ,  Jinglai Hao ,  Dahai Wang

发明人： Wensheng Yu ,  Joseph A. Kozlowski ,  Ling Tong ,  Craig A. Cobum ,  Bin Hu ,  Bin Zhong ,  Jinglai Hao ,  Dahai Wang

IPC分类号： C07D498/04 ,  A61K31/5365 ,  A61K31/496 ,  A61K45/06 ,  A61P31/14

摘要： The present invention relates to novel Chromane-Substituted Tetracyclic Compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, A′, R2 R3, R4 and R5 are as defined herein. The present invention also relates to compositions comprising a Chromane-Substituted Tetracyclic Compound, and methods of using the Chromane-Substituted Tetracyclic Compounds for treating or preventing HCV infection in a patient.

公开(公告)号：US20170217940A1

公开(公告)日：2017-08-03

申请号：US15104584

申请日：2014-12-15

申请人： Joseph KOZLOWSKI ,  Craig COBURN ,  Wensheng YU ,  Bin HU ,  Bin ZHONG ,  Jinglai HAO ,  Dahai WANG ,  Tao JI ,  MERCL SHARP & DOHME CORP.

发明人： Joseph Kozlowski ,  Craig Coburn ,  Wensheng Yu ,  Ling Tong ,  Bin Hu ,  Bin Zhong ,  Jinglai Hao ,  Dahai Wang ,  Tao Ji

IPC分类号： C07D405/14 ,  A61K31/4178 ,  A61K31/7072 ,  A61K45/06 ,  A61K31/4985

CPC分类号： C07D405/14 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4985 ,  A61K31/7072 ,  A61K45/06 ,  C07D493/04 ,  A61K2300/00

摘要： The present invention relates to novel Fused Tetracyclic Heterocyclic Compounds of Formula I: (I), wherein A, A′, R2A, R2B, R7, R8, R9, and R10 are defined herein. The compounds and their pharmaceutically acceptable salts are useful for the prophylaxis or treatment of infection by HCV and the prophylaxis, treatment, or delay in the onset of disease caused by HCV. The present invention also relates to pharmaceutical compositions comprising at least one Fused Tetracyclic Heterocyclic Compound, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines, and methods of using the Fused Tetracyclic Heterocyclic Compounds for treating or preventing HCV infection in a patient.

公开(公告)号：US09828365B2

公开(公告)日：2017-11-28

申请号：US15104584

申请日：2014-12-15

申请人： MERCK SHARP & DOHME CORP. ,  Joseph Kozlowski ,  Craig Coburn ,  Wensheng Yu ,  Ling Tong ,  Bin Hu ,  Bin Zhong ,  Jinglai Hao ,  Dahai Wang ,  Tao Ji

发明人： Joseph Kozlowski ,  Craig Coburn ,  Wensheng Yu ,  Ling Tong ,  Bin Hu ,  Bin Zhong ,  Jinglai Hao ,  Dahai Wang ,  Tao Ji

IPC分类号： C07D493/04 ,  C07D405/14 ,  A61K45/06 ,  A61K31/4985 ,  A61K31/7072 ,  A61K31/4178

CPC分类号： C07D405/14 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4985 ,  A61K31/7072 ,  A61K45/06 ,  C07D493/04 ,  A61K2300/00

摘要： The present invention relates to novel Fused Tetracyclic Heterocyclic Compounds of Formula I: (I), wherein A, A′, R2A, R2B, R7, R8, R9, and R10 are defined herein. The compounds and their pharmaceutically acceptable salts are useful for the prophylaxis or treatment of infection by HCV and the prophylaxis, treatment, or delay in the onset of disease caused by HCV. The present invention also relates to pharmaceutical compositions comprising at least one Fused Tetracyclic Heterocyclic Compound, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines, and methods of using the Fused Tetracyclic Heterocyclic Compounds for treating or preventing HCV infection in a patient.

公开(公告)号：US20080102497A1

公开(公告)日：2008-05-01

申请号：US11619314

申请日：2007-01-03

申请人： Dominic Wong ,  Arun Kumar Uppalanchi ,  Xiangdong Gan ,  Bin Zhong

发明人： Dominic Wong ,  Arun Kumar Uppalanchi ,  Xiangdong Gan ,  Bin Zhong

IPC分类号： C12P19/04 ,  C12P19/02 ,  C12N9/32

CPC分类号： C12P19/14 ,  C12P19/20 ,  C12P19/22

摘要： Provided herein are methods of increasing the enzymatic rate of hydrolysis of starch substrates. In certain embodiments the method comprises contacting a starch substrate with one or more amylase family enzymes in the presence of greater than 0.001 mM manganese ions. In certain embodiments, the method comprises contacting a starch substrate with one or more glucoamylase and/or β-amylase enzymes in the presence of greater than 0.001 mM calcium ions (Ca++). In certain embodiments, the method comprises contacting the starch substrate with a β-amylase in the presence of greater than 0.001 mM manganese ion, calcium ion, magnesium ion (Mg++), strontium ion (Sr++), barium ion (Ba++) or any combination of said metal ions. In certain embodiments the method comprises contacting the starch substrate with a glucoamylase in the presence of greater than 0.001 mM manganese ion, calcium ion, lithium ion (Li+), potassium ion (K+), or any combination of said metal ions. Also provided herein are compositions and kits for hydrolyzing starch.

摘要翻译： 本文提供了增加淀粉底物的酶水解速率的方法。 在某些实施方案中，该方法包括在大于0.001mM锰离子的存在下使淀粉底物与一种或多种淀粉酶家族酶接触。 在某些实施方案中，该方法包括在大于0.001mM钙离子（Ca ++）的存在下使淀粉底物与一种或多种葡糖淀粉酶和/或β-淀粉酶接触。 在某些实施方案中，该方法包括在大于0.001mM的锰离子，钙离子，镁离子（Mg ++），锶离子（Sr < SUP + ++），钡离子（Ba ++）或所述金属离子的任何组合。 在某些实施方案中，所述方法包括在大于0.001mM的锰离子，钙离子，锂离子（Li +）和/或离子（K +）的存在下使淀粉底物与葡糖淀粉酶接触， / SUP>）或所述金属离子的任何组合。 本文还提供用于水解淀粉的组合物和试剂盒。