公开(公告)号：US11091493B2

公开(公告)日：2021-08-17

申请号：US16914138

申请日：2020-06-26

申请人： Merck Sharp & Dohme Corp.

发明人： Feng Xu ,  Zhuqing Liu ,  Richard Desmond ,  Jeonghan Park ,  Alexei Kalinin ,  Birgit Kosjek ,  Hallena Strotman ,  Hongmei Li ,  Johannah Moncecchi

IPC分类号： C07D487/04 ,  C07D207/08 ,  C07C215/30 ,  C07D207/12 ,  C12P17/10

摘要： The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KED) biocatalyst enzymes and methods of using the biocatalysts.

公开(公告)号：US10287289B2

公开(公告)日：2019-05-14

申请号：US14776366

申请日：2014-03-12

申请人： Merck Sharp & Dohme Corp.

发明人： Feng Xu ,  Zhuqing Liu ,  Richard Desmond ,  Jeonghan Park ,  Alexei Kalinin ,  Birgit Kosjek ,  Hallena Strotman ,  Hongmei Li ,  Johannah Moncecchi

IPC分类号： C12P17/10 ,  C12P7/22 ,  C12N9/02 ,  C12N15/09 ,  C07D487/04 ,  C07D207/08 ,  C07C215/30 ,  C07D207/12

摘要： The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts.

公开(公告)号：US10150959B2

公开(公告)日：2018-12-11

申请号：US14771511

申请日：2014-03-12

申请人： Merck Sharp & Dohme Corp.

发明人： Matthew D. Truppo ,  Hongmei Li ,  Johannah R. Moncecchi ,  Hallena Strotman

IPC分类号： C12N9/04 ,  C12N11/08 ,  C12P7/02 ,  C12P7/22

摘要： The invention is directed to immobilized ketoreductases and methods of making and using them. Enzymes are protein molecules which serve to accelerate the chemical reactions of living cells (often by several orders of magnitude). Without enzymes, most biochemical reactions would be too slow to even carry out life processes. Enzymes display great specificity and are not permanently modified by their participation in reactions. Since they are not changed during the reactions, enzymes can be cost effectively used as catalysts for a desired chemical transformation.

公开(公告)号：US20170145014A1

公开(公告)日：2017-05-25

申请号：US14776366

申请日：2014-03-12

申请人： Merck Sharp & Dohme Corp.

发明人： Feng Xu ,  Zhuqing Liu ,  Richard Desmond ,  Jeonghan Park ,  Alexei Kalinin ,  Birgit Kosjek ,  Hallena Strotman ,  Hongmei Li ,  Johannah Moncecchi

IPC分类号： C07D487/04 ,  C07C215/30 ,  C12P17/10 ,  C07D207/12

CPC分类号： C07D487/04 ,  C07C215/30 ,  C07D207/08 ,  C07D207/12 ,  C12P17/10

摘要： The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of 1-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts.

公开(公告)号：US10696681B2

公开(公告)日：2020-06-30

申请号：US16298467

申请日：2019-03-11

申请人： Merck Sharp & Dohme Corp.

发明人： Feng Xu ,  Zhuqing Liu ,  Richard Desmond ,  Jeonghan Park ,  Alexei Kalinin ,  Birgit Kosjek ,  Hallena Strotman ,  Hongmei Li ,  Johannah Moncecchi

IPC分类号： C07D487/04 ,  C07D207/08 ,  C07C215/30 ,  C07D207/12 ,  C12P17/10

摘要： The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts.

公开(公告)号：US20190194211A1

公开(公告)日：2019-06-27

申请号：US16298467

申请日：2019-03-11

申请人： Merck Sharp & Dohme Corp.

发明人： Feng Xu ,  Zhuqing Liu ,  Richard Desmond ,  Jeonghan Park ,  Alexei Kalinin ,  Birgit Kosjek ,  Hallena Strotman ,  Hongmei Li ,  Johannah Moncecchi

IPC分类号： C07D487/04 ,  C12P17/10 ,  C07D207/08 ,  C07C215/30 ,  C07D207/12

摘要： The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts.

公开(公告)号：US11649243B2

公开(公告)日：2023-05-16

申请号：US17399274

申请日：2021-08-11

申请人： Merck Sharp & Dohme Corp.

发明人： Feng Xu ,  Zhuqing Liu ,  Richard Desmond ,  Jeonghan Park ,  Alexei Kalinin ,  Birgit Kosjek ,  Hallena Strotman ,  Hongmei Li ,  Johannah Moncecchi

IPC分类号： C07D487/04 ,  C07D207/08 ,  C07C215/30 ,  C07D207/12 ,  C12P17/10

CPC分类号： C07D487/04 ,  C07C215/30 ,  C07D207/08 ,  C07D207/12 ,  C12P17/10

摘要： The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts.

公开(公告)号：US09725464B2

公开(公告)日：2017-08-08

申请号：US15032552

申请日：2014-10-24

申请人： MERCK SHARP & DOHME CORP.

发明人： Ian Mangion ,  Cheng-yi Chen ,  Ingyu Jeon ,  Yonggang Chen ,  Hongmei Li ,  Hoa N. Nguyen ,  Peter E. Maligres ,  Artis Klapars ,  Ilia Zavialov ,  Nobuyoshi Yasuda

IPC分类号： C07D498/04 ,  C07D403/04 ,  C07C215/50 ,  C07F5/02 ,  C07C213/02

CPC分类号： C07D498/04 ,  C07C213/02 ,  C07C215/50 ,  C07D403/04 ,  C07F5/025

摘要： The present invention is directed to a process for preparing Tetracyclic Heterocycle Compounds of formula (I): which are useful as HCV NS5A inhibitors. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

公开(公告)号：US20160257698A1

公开(公告)日：2016-09-08

申请号：US15032552

申请日：2014-10-24

申请人： Merck Sharp & Dohme Corp.

发明人： Ian Mangion ,  Cheng-yi Chen ,  Ingyu Jeon ,  Yonggang Chen ,  Hongmei Li ,  Hoa N. Nguyen ,  Peter E. Maligres ,  Artis Klapars ,  Ilia Zavialov ,  Nobuyoshi Yasuda

IPC分类号： C07D498/04 ,  C07D403/04 ,  C07C213/02

CPC分类号： C07D498/04 ,  C07C213/02 ,  C07C215/50 ,  C07D403/04 ,  C07F5/025

摘要： The present invention is directed to a process for preparing Tetracyclic Heterocycle Compounds of formula (I): which are useful as HCV NS5A inhibitors. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

摘要翻译： 本发明涉及制备式（I）的四环杂环化合物的方法：其可用作HCV NS5A抑制剂。 本发明还涉及可用作制备式（I）化合物的合成中间体的化合物。

公开(公告)号：US20160053251A1

公开(公告)日：2016-02-25

申请号：US14771511

申请日：2014-03-12

申请人： Merck Sharp & Dohme Corp.

发明人： Matthew D. Truppo ,  Hongmei Li ,  Johannah R. Moncecchi ,  Hallena Strotman

IPC分类号： C12N11/08 ,  C12N9/04 ,  C12P7/22

CPC分类号： C12N11/08 ,  C12N9/0006 ,  C12P7/02 ,  C12P7/22

摘要： The invention is directed to immobilized ketoreductases and methods of making and using them. Enzymes are protein molecules which serve to accelerate the chemical reactions of living cells (often by several orders of magnitude). Without enzymes, most biochemical reactions would be too slow to even carry out life processes. Enzymes display great specificity and are not permanently modified by their participation in reactions. Since they are not changed during the reactions, enzymes can be cost effectively used as catalysts for a desired chemical transformation.

摘要翻译： 本发明涉及固定的酮还原酶及其制备和使用方法。 酶是蛋白质分子，用于加速活细胞的化学反应（通常是几个数量级）。 没有酶，大多数生物化学反应将太慢，甚至不能进行生命过程。 酶显示出极大的特异性，并且不被参与反应永久地改变。 由于它们在反应期间没有改变，因此可以成本有效地使用酶作为所需化学转化的催化剂。