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：US20150105354A1

公开(公告)日：2015-04-16

申请号：US14575418

申请日：2014-12-18

Applicant: Merck Sharp & Dohme Corp. ,  Pharmacopeia, LLC

Inventor： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voigt ,  Corey Strickland ,  Elizabeth M. Smith ,  Andrew W. Stamford ,  William J. Greenlee ,  Robert D. Mazzola, JR. ,  John Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy X.H. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachael C. Hunter

IPC: C07D233/88 ,  C07D401/04 ,  A61K31/4439 ,  C07D405/06 ,  A61K31/4178 ,  C07D401/06 ,  A61K31/454 ,  C07D407/06 ,  C07D403/06 ,  A61K31/5377 ,  C07D235/02 ,  A61K31/4184 ,  A61K31/655 ,  C07D405/14 ,  C07D401/14 ,  A61K31/4545 ,  A61K31/4725 ,  A61K45/06 ,  A61K31/4168

CPC classification number: C07D233/88 ,  A61K31/4168 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/655 ,  A61K45/06 ,  C07D233/46 ,  C07D233/70 ,  C07D235/02 ,  C07D239/22 ,  C07D239/70 ,  C07D271/07 ,  C07D273/00 ,  C07D295/15 ,  C07D401/04 ,  C07D401/06 ,  C07D401/08 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/10 ,  C07D403/12 ,  C07D405/06 ,  C07D405/10 ,  C07D405/14 ,  C07D407/06 ,  C07D409/04 ,  C07D409/06 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06 ,  Y02A50/411

Abstract: Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O)2—, —C(═O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(═N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(═O)— or —C(═NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(═NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes.Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.

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：US09416129B2

公开(公告)日：2016-08-16

申请号：US14433298

申请日：2013-10-14

Applicant: Merck Sharp & Dohme Corp.

Inventor： Eric J. Gilbert ,  Jared N. Cumming ,  Andrew W. Stamford ,  Younong Yu ,  Jack D. Scott ,  Ulrich Iserloh ,  Lingyan Wang ,  John P. Caldwell

IPC: C07D417/14 ,  C07D417/10 ,  C07D417/04 ,  A61K31/549 ,  A61K45/06 ,  C07D495/04

CPC classification number: C07D417/14 ,  A61K31/549 ,  A61K45/06 ,  C07D417/10 ,  C07D495/04

Abstract: In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): (I) and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein the middle ring (referred to herein as “ring B”) of the tricyclic substituent is an optionally substituted 6-membered ring, and each of the remaining variables shown in the formula are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

Abstract translation: 在其许多实施方案中，本发明提供了某些亚氨基噻嗪二氧化物化合物，包括式（I）化合物：（I）及其互变异构体和立体异构体，以及所述化合物，所述互变异构体和所述立体异构体的药学上可接受的盐，其中中环 在本文中作为“环B”）是三环取代基是任选取代的6元环，并且式中所示的各个残基如本文所定义。 本发明的新化合物可用作BACE抑制剂和/或用于治疗和预防与其相关的各种病症。 还公开了包含一种或多种这样的化合物（单独和与一种或多种其它活性剂组合）的药物组合物及其制备和使用方法，包括阿尔茨海默氏病。

公开(公告)号：US20150284379A1

公开(公告)日：2015-10-08

申请号：US14433298

申请日：2013-10-14

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Eric J. Gilbert ,  Jared N. Cumming ,  Andrew W. Stamford ,  Younong Yu ,  Jack D. Scott ,  Ulrich Iserloh ,  Lingyan Wang ,  John P. Caldwell

IPC: C07D417/14 ,  A61K45/06 ,  C07D495/04 ,  A61K31/549 ,  C07D417/10

CPC classification number: C07D417/14 ,  A61K31/549 ,  A61K45/06 ,  C07D417/10 ,  C07D495/04

Abstract: In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): (I) and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein the middle ring (referred to herein as “ring B”) of the tricyclic substituent is an optionally substituted 6-membered ring, and each of the remaining variables shown in the formula are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

Abstract translation: 在其许多实施方案中，本发明提供了某些亚氨基噻嗪二氧化物化合物，包括式（I）化合物：（I）及其互变异构体和立体异构体，以及所述化合物，所述互变异构体和所述立体异构体的药学上可接受的盐，其中中环 在本文中作为“环B”）是三环取代基是任选取代的6元环，并且式中所示的各个残基如本文所定义。 本发明的新化合物可用作BACE抑制剂和/或用于治疗和预防与其相关的各种病症。 还公开了包含一种或多种这样的化合物（单独和与一种或多种其它活性剂组合）的药物组合物及其制备和使用方法，包括阿尔茨海默氏病。