公开(公告)号：US10526363B2

公开(公告)日：2020-01-07

申请号：US15503776

申请日：2015-08-14

申请人： Merck Sharp & Dohme Corp. ,  Merck Sharp & Dohme Limited ,  John Simon Edwards ,  Peter Richard Mullens ,  Edward Cleator ,  Bryon L. Simmons ,  Courtney K. Maguire ,  Jeremy Peter Scott ,  Nobuyoshi Yasuda ,  Yong-Li Zhong ,  Lisa F. Frey ,  Peter G. Dormer ,  Andrew Brunskill ,  Artis Klapars ,  Pu Qian ,  Yi Zhang ,  Baoqiang Wan ,  Eric Ashley

发明人： John Simon Edwards ,  Peter Richard Mullens ,  Edward Cleator ,  Bryon L. Simmons ,  Courtney K. Maguire ,  Jeremy Peter Scott ,  Nobuyoshi Yasuda ,  Yong-Li Zhong ,  Lisa F. Frey ,  Peter G. Dormer ,  Andrew Brunskill ,  Artis Klapars ,  Pu Qian ,  Yi Zhang ,  Baoqiang Wan ,  Eric Ashley

IPC分类号： C07H19/10 ,  C07F9/58 ,  C07H19/06 ,  C07F9/24 ,  C07F9/6558

摘要： The present invention is directed to Compounds of Formula (I) and salts thereof, wherein R1, R2, R3 and R4 are defined above herein. The present invention is also directed to uses of the compounds of Formula (I) to add phosphoramidate groups onto organic alcohols.

公开(公告)号：US20170275327A1

公开(公告)日：2017-09-28

申请号：US15503776

申请日：2015-08-14

申请人： John Simon EDWARDS ,  Peter Richard MULLENS ,  Edward CLEATOR ,  Bryon L. SIMMONS ,  Courtney K. MAGUIRE ,  Jeremy Peter SCOTT ,  Nobuyoshi YASUDA ,  Yong ZHONG ,  Lisa F. FREY ,  Peter G. DORMER ,  Andrew BRUNSKILL ,  Artis KLAPARS ,  Eric ASHLEY ,  Pu QIAN ,  Yi ZHANG ,  Baoqiang WAN ,  MERCK SHARP & DOHME CORP. ,  MERCK SHARP & DOHME LIMITED

发明人： John Edwards ,  Peter Richard Mullens ,  Ed Cleator ,  Bryon L. Simmons ,  Courtney K. Maguire ,  Jeremy Peter Scott ,  Nobuyoshi Yasuda ,  Yong-Li Zhong ,  Lisa F. Frey ,  Peter G. Dormer ,  Andrew Brunskill ,  Artis Klapars ,  Puneet Qian ,  Yi Zhang ,  Baoqiang Wan

IPC分类号： C07H19/10 ,  C07F9/24 ,  C07F9/58

CPC分类号： C07H19/10 ,  C07F9/242 ,  C07F9/2458 ,  C07F9/2487 ,  C07F9/58 ,  C07F9/65586 ,  C07H19/06

摘要： The present invention is directed to Compounds of Formula (I) and salts thereof, wherein R1, R2, R3 and R4 are defined above herein. The present invention is also directed to uses of the compounds of Formula (I) to add phosphoramidate groups onto organic alcohols.

公开(公告)号：US20130164794A1

公开(公告)日：2013-06-27

申请号：US13817295

申请日：2011-08-08

申请人： John Limanto ,  Gregory Beutner ,  Brendan Grau ,  Jacob Janey ,  Artis Klapars ,  Eric Ashley ,  Hallena R. Strotman ,  Matthew D. Truppo ,  Gregory Hughes ,  Fabien L. Cabirol ,  Anupam Gohel ,  Steven J. Collier ,  Jack Liang ,  Marissa Mock ,  Emily Mundorff ,  Scott Novick ,  Derek Smith

发明人： John Limanto ,  Gregory Beutner ,  Brendan Grau ,  Jacob Janey ,  Artis Klapars ,  Eric Ashley ,  Hallena R. Strotman ,  Matthew D. Truppo ,  Gregory Hughes ,  Fabien L. Cabirol ,  Anupam Gohel ,  Steven J. Collier ,  Jack Liang ,  Marissa Mock ,  Emily Mundorff ,  Scott Novick ,  Derek Smith

IPC分类号： C12N9/10

CPC分类号： C12P13/001 ,  C12N9/1096

摘要： The disclosure provides transaminase polypeptides capable of converting the substrate, 2-(3,4-dimethoxyphenethoxy)cyclohexanone to the trans diastereomer product (1R,2R)-2-(3,4-dimethoxyphenethoxy)cyclohexanamine in at least a 2:1 diastereomeric ratio relative to the cis diastereomer (1R,2S)-2-(3,4-dimethoxyphenethoxy)cyclohexanamine. The disclosure also provides polynucleotides, vectors, host cells, and methods of making and using the transaminase polypeptides in processes for preparing (1R,2R)-2-(3,4-dimethoxyphenethoxy)cyclohexanamine and its analogs, which can product compounds can be further used to prepare the aminocyclohexylether compound, (3R)-1-[(1R,2R)-2-[2-(3,4-dimethoxyphenyl)ethoxy]cyclohexyl]pyrrolidin-3-ol, which is an ion channel blocker.

摘要翻译： 本公开提供能够将底物2-（3,4-二甲氧基苯乙氧基）环己酮转化成至少2:1非对映异构体的反式非对映异构体产物（1R，2R）-2-（3,4-二甲氧基苯乙氧基）环己胺的转氨酶多肽 比例相对于顺式非对映体（1R，2S）-2-（3,4-二甲氧基苯乙氧基）环己胺。 本公开还提供了多核苷酸，载体，宿主细胞，以及在制备（1R，2R）-2-（3,4-二甲氧基苯乙氧基）环己胺及其类似物的方法中制备和使用转氨酶多肽的方法，产物化合物可以是 进一步用于制备作为离子通道阻断剂的氨基环己基醚化合物（3R）-1 - [（1R，2R）-2- [2-（3,4-二甲氧基苯基）乙氧基]环己基]吡咯烷-3-醇。