公开(公告)号：US09732111B2

公开(公告)日：2017-08-15

申请号：US14443922

申请日：2013-11-14

Applicant: Merck Sharp & Dohme Corp.

Inventor： Frank Bennett ,  Yuhua Huang ,  Lingyan Wang ,  Stephane L. Bogen ,  Angela D. Kerekes ,  Vinay M. Girijavallabhan ,  Gabor Butora ,  Quang Truong ,  Ian Davies ,  Ann E. Weber

IPC: A01N43/04 ,  A61K31/70 ,  C07H19/10 ,  A61K45/06 ,  A61K31/7072 ,  C07H19/06 ,  C07H19/067 ,  C07H19/09 ,  C07H19/11 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7068

CPC classification number: C07H19/10 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7072 ,  A61K45/06 ,  C07H19/06 ,  C07H19/067 ,  C07H19/09 ,  C07H19/11

Abstract: The present invention relates to 2′-Alkynyl Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein B, X, R1, R2, R3 and R4 are as defined herein. The present invention also relates to compositions comprising at least one 2′-Alkynyl Substituted Nucleoside Derivative, and methods of using the 2′-Alkynyl Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.

公开(公告)号：US20170197964A1

公开(公告)日：2017-07-13

申请号：US15323985

申请日：2015-07-09

Applicant: Merck Sharp & Dohme Corp.

Inventor： Alexander Pasternak ,  Ian Davies ,  Fa-Xiang Ding ,  Jinglong Jiang ,  Shuzhi Dong ,  Xin Gu

IPC: C07D471/10 ,  A61K31/444 ,  A61K45/06 ,  A61K31/438

CPC classification number: C07D471/10 ,  A61K31/438 ,  A61K31/444 ,  A61K45/06

Abstract: 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：US20160045526A1

公开(公告)日：2016-02-18

申请号：US14436687

申请日：2013-10-11

Applicant: Merck Sharp & Dohme Corp.

Inventor： Vinay Girijavallabhan ,  Stephane Bogen ,  Weidong Pan ,  Qun Dang ,  Ian Davies

IPC: A61K31/706 ,  A61K31/7056 ,  A61K45/06 ,  C07H7/06

CPC classification number: A61K31/706 ,  A61K31/7056 ,  A61K38/21 ,  A61K45/06 ,  C07D487/04 ,  C07H7/06 ,  A61K2300/00

Abstract: 2′-disubstituted substituted nucleoside derivatives of formula (I) and pharmaceutically acceptable salts thereof are disclosed: (1), wherein A is N3 or NH2 and X, Y, R1, R2, R3, R4, R5 and R18 are as defined herein. Compositions comprising at least one 2′-disubstituted nucleoside derivative, and methods of using the 2′-disubstituted nucleoside derivatives for treating or preventing HCV infection in a patient are disclosed.

Abstract translation: 公开了式（I）的2'-二取代取代的核苷衍生物及其药学上可接受的盐：（1）其中A是N 3或NH 2，X，Y，R 1，R 2，R 3，R 4，R 5和R 18如本文所定义 。 公开了包含至少一种2'-二取代核苷衍生物的组合物，以及使用2'-二取代核苷衍生物治疗或预防患者HCV感染的方法。

公开(公告)号：US09926317B2

公开(公告)日：2018-03-27

申请号：US15323985

申请日：2015-07-09

Applicant: Merck Sharp & Dohme Corp.

Inventor： Alexander Pasternak ,  Ian Davies ,  Fa-Xiang Ding ,  Jinglong Jiang ,  Shuzhi Dong ,  Xin Gu

IPC: C07D471/10 ,  A61K31/438 ,  A61K31/444 ,  A61K45/06

CPC classification number: C07D471/10 ,  A61K31/438 ,  A61K31/444 ,  A61K45/06

Abstract: 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：US20160122380A1

公开(公告)日：2016-05-05

申请号：US14899008

申请日：2014-06-16

Applicant: Merck Sharp & Dohme Corp.

Inventor： Stephane Bogen ,  Vinay Girijavallabhan ,  Quang Truong ,  Ping Chen ,  Frank Bennett ,  Angela Kerekes ,  Qun Dang ,  David B. Olsen ,  Ian Davies

IPC: C07H19/10 ,  A61K45/06 ,  A61K31/7072

CPC classification number: C07H19/10 ,  A61K31/661 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7072 ,  A61K45/06 ,  C07F9/65586 ,  C07F9/65744 ,  C07H19/11 ,  A61K2300/00

Abstract: The present invention relates to Cyclic Phosphonate Substituted Nucleoside Derivatives of Formula (I): (structure) and pharmaceutically acceptable salts thereof, wherein B, X, R1, R2 and R3 are as defined herein, as well as to compositions and methods of using the Cyclic Phosphonate Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.

Abstract translation: 本发明涉及式（I）的环磷酸酯取代的核苷衍生物：（结构）及其药学上可接受的盐，其中B，X，R 1，R 2和R 3如本文所定义，以及使用 用于治疗或预防患者HCV感染的环磷酸酯取代的核苷衍生物。

公开(公告)号：US10131674B2

公开(公告)日：2018-11-20

申请号：US15524872

申请日：2015-11-05

Applicant: Merck Sharp & Dohme Corp.

Inventor： Daniel A. DiRocco ,  Ian Davies ,  Feng Peng ,  Mark McLaughlin ,  Louis-Charles Campeau ,  Yingju Xu

IPC: C07D498/04 ,  B01J31/18 ,  B01J35/00

Abstract: The present invention is directed to a process for preparing Substituted Indole Compounds of Formula (I): wherein R1, R2, R3 and R4 are as defined herein. These indole compounds are useful as synthetic intermediates for making inhibitors of HCV NS5A.

公开(公告)号：US20170334926A1

公开(公告)日：2017-11-23

申请号：US15524872

申请日：2015-11-05

Applicant: Daniel A. DIROCCO ,  Ian DAVIES ,  Feng PENG ,  Mark MCLAUGHLIN ,  Louis-Charles CAMPEAU ,  Yingju XU ,  Merck Sharp & Dohme Corp.

Inventor： Daniel A . DiRocco ,  Ian Davies ,  Feng Peng ,  Mark McLaughlin ,  Louis-Charles Campeau ,  Yingju Xu

IPC: C07D498/04 ,  B01J31/18 ,  B01J35/00

CPC classification number: C07D498/04 ,  B01J31/00 ,  B01J31/181 ,  B01J35/004 ,  B01J2231/766 ,  B01J2531/827

Abstract: The present invention is directed to a process for preparing Substituted Indole Compounds of Formula (I): wherein R1, R2, R3 and R4 are as defined herein. These indole compounds are useful as synthetic intermediates for making inhibitors of HCV NS5A.

公开(公告)号：US09242988B2

公开(公告)日：2016-01-26

申请号：US14436697

申请日：2013-10-11

Applicant: Merck Sharp & Dohme Corp.

Inventor： Vinay Girijavallabhan ,  Stephane Bogen ,  Weidong Pan ,  Qun Dang ,  Ian Davies

IPC: C07H19/12 ,  C07H19/23 ,  A61K31/7052 ,  A61P31/14 ,  C07D487/04 ,  A61K38/21 ,  A61K45/06 ,  A61K31/7056 ,  A61K31/706 ,  A61K47/48 ,  C07F9/6561 ,  C07F9/6574

CPC classification number: C07D487/04 ,  A61K31/7056 ,  A61K31/706 ,  A61K38/212 ,  A61K45/06 ,  A61K47/48215 ,  A61K47/60 ,  C07F9/65616 ,  C07F9/65744 ,  A61K2300/00

Abstract: Compounds of Formula (I) are disclosed, wherein R1, R2, R3, R4, R5, and R18 are defined herein. The compounds encompassed by Formula (I) include compounds which are HCV NS5B inhibitors and other compounds which can be metabolized in vivo to HCV NS5B inhibitors. 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 compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

Abstract translation: 公开了式（I）的化合物，其中R 1，R 2，R 3，R 4，R 5和R 18在本文中定义。 由式（I）包括的化合物包括HCV NS5B抑制剂和可以在体内被代谢为HCV NS5B抑制剂的其它化合物。 该化合物及其药学上可接受的盐可用于预防或治疗HCV的感染以及由HCV引起的疾病发作的预防，治疗或延迟。 化合物及其盐可以用作药物组合物中的成分，任选与其它抗病毒剂，免疫调节剂，抗生素或疫苗组合使用。

公开(公告)号：US20150299243A1

公开(公告)日：2015-10-22

申请号：US14443922

申请日：2013-11-14

Applicant: Frank BENNETT ,  Yuhua HUANG ,  Lingyan WANG ,  Stephane L. BOGEN ,  Angela D. KEREKES ,  Vinay M. GIRIJAVALLABHAN ,  Gabor BUTORA ,  Quang TRUONG ,  Ian DAVIES ,  Anne E. WEBER ,  MERCK SHARP & DOHME CORP.

Inventor： Frank Bennett ,  Yuhua Huang ,  Lingyan Wang ,  Stephane L. Bogen ,  Angela D. Kerekes ,  Vinay M. Girijavallabhan M. Girijavallabhan ,  Gabor Butora ,  Quang Truong ,  Ian Davies ,  Ann E. Weber

IPC: C07H19/10 ,  A61K31/7072 ,  A61K45/06 ,  C07H19/06

CPC classification number: C07H19/10 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7072 ,  A61K45/06 ,  C07H19/06 ,  C07H19/067 ,  C07H19/09 ,  C07H19/11

Abstract: The present invention relates to 2′-Alkynyl Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein B, X, R1, R2, R3 and R4 are as defined herein. The present invention also relates to compositions comprising at least one 2′-Alkynyl Substituted Nucleoside Derivative, and methods of using the 2′-Alkynyl Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.

Abstract translation: 本发明涉及式（I）的2'-炔炔基取代的核苷衍生物及其药学上可接受的盐，其中B，X，R 1，R 2，R 3和R 4如本文所定义。 本发明还涉及包含至少一种2'-炔基取代的核苷衍生物的组合物，以及使用2'-炔基取代的核苷衍生物治疗或预防患者HCV感染的方法。

公开(公告)号：US10208064B2

公开(公告)日：2019-02-19

申请号：US15323989

申请日：2015-07-09

Applicant: MERCK SHARP & DOHME CORP. ,  Alexander Pasternak ,  Ian Davies ,  Fa-Xiang Ding ,  Jinlong Jiang ,  Shuzhi Dong ,  Xin Gu ,  Takao Suzuki ,  Joseph P. Vacca ,  Zhifa Pu ,  Shouning Xu

Inventor： Alexander Pasternak ,  Ian Davies ,  Fa-Xiang Ding ,  Jinlong Jiang ,  Shuzhi Dong ,  Xin Gu ,  Takao Suzuki ,  Joseph P. Vacca ,  Zhifa Pu ,  Shouning Xu

IPC: C07D513/10 ,  C07D519/00 ,  A61K45/06 ,  A61K31/435 ,  A61K31/4745 ,  A61K31/4375

Abstract: 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.