公开(公告)号：US11008313B2

公开(公告)日：2021-05-18

申请号：US16334605

申请日：2017-09-15

Applicant: Merck Sharp & Dohme Corp.

Inventor： Jason Eugene Imbriglio ,  Whitney Lane Petrilli ,  Yusheng Xiong ,  Zhe Feng ,  Hyewon Youm ,  Wonsuk Chang ,  Rui Liang ,  Zhijian Lu ,  Jerry Andrew Taylor ,  Scott B. Hoyt

IPC: C07D417/12 ,  G01N33/58

Abstract: The present invention relates to PCSK9 allosteric binding compounds of Formula I: (Formula (I)) and pharmaceutically acceptable salts thereof, wherein X1, X2, Y, R1, R2, RA, RB and n are as defined herein. The present invention also relates to compositions which comprise an allosteric binding compound of the invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The invention further relates, inter alia, to methods for inducing PCSK9 protein degradation in a subject, and methods for treating atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions, comprising administering to a subject an effective amount of a compound or a pharmaceutically acceptable salt of the invention. The invention also provides a means for the in vitro labeling, detection and/or quantification of PCSK9 in biological samples.

公开(公告)号：US10759825B2

公开(公告)日：2020-09-01

申请号：US15886568

申请日：2018-02-01

Applicant: Merck Sharp & Dohme Corp.

Inventor： Michael D. Altman ,  Brian Andresen ,  Wonsuk Chang ,  Matthew Lloyd Childers ,  Jared N. Cumming ,  James P. Jewell ,  Jongwon Lim ,  Alan B. Northrup ,  Ryan D. Otte ,  Benjamin Wesley Trotter ,  Quang T. Truong ,  Shawn P. Walsh ,  Kake Zhao

IPC: A01N43/04 ,  A61K31/70 ,  C07H21/04 ,  C07H21/02 ,  A61K39/39 ,  C07H19/20 ,  C07H19/23 ,  C07H21/00 ,  A61P35/00 ,  A61K31/7064 ,  A61K31/7084 ,  A61K31/708 ,  A61K31/706 ,  A61K31/7076

Abstract: A class of polycyclic compounds of general formula (I), of general formula (I′), or of general formula (I″), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3, R4, R4a, R5, R6, R6a, R7, R7a, R8, and R8a are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.

公开(公告)号：US10738074B2

公开(公告)日：2020-08-11

申请号：US15752144

申请日：2016-08-11

Applicant: Merck Sharp & Dohme Corp. ,  Michael D. Altman ,  Brian Andresen ,  Wonsuk Chang ,  Matthew Lloyd Childers ,  Jared N. Cumming ,  Andrew Marc Haidle ,  Timothy J. Henderson ,  James P. Jewell ,  Min Lu ,  Alan B. Northrup ,  Ryan D. Otte ,  Tony Siu ,  Benjamin Wesley Trotter ,  Quang T. Truong

Inventor： Michael D. Altman ,  Brian Andresen ,  Wonsuk Chang ,  Matthew Lloyd Childers ,  Jared N. Cumming ,  Andrew Marc Haidle ,  Timothy J. Henderson ,  James P. Jewell ,  Min Lu ,  Alan B. Northrup ,  Ryan D. Otte ,  Tony Siu ,  Benjamin Wesley Trotter ,  Quang T. Truong

IPC: A01N43/04 ,  A61K31/70 ,  C07H21/04 ,  C07H21/02 ,  A61K39/39 ,  C07H19/20 ,  C07H19/23 ,  C07H21/00 ,  A61P35/00 ,  A61K31/7064 ,  A61K31/7084 ,  A61K31/708 ,  A61K31/706 ,  A61K31/7076

Abstract: A class of polycyclic compounds of general formula (II), of general formula (II′), or of general formula (II″), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3a, R4, R4a, R5, R6, R6a, R7, R7a, R8, and R8a are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.

公开(公告)号：US10414747B2

公开(公告)日：2019-09-17

申请号：US15722093

申请日：2017-10-02

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Michael D. Altman ,  Brandon D. Cash ,  Wonsuk Chang ,  Jared N. Cumming ,  Andrew M. Haidle ,  Timothy J. Henderson ,  James P. Jewell ,  Matthew A. Larsen ,  Rui Liang ,  Jongwon Lim ,  Min Lu ,  Ryan D. Otte ,  Tony Siu ,  Benjamin Wesley Trotter ,  Sriram Tyagarajan

IPC: C07D333/60 ,  C07D333/62 ,  C07D409/12 ,  C07D498/04

Abstract: Compounds of general formula (Ia), compounds of general formula (Ia′), compounds of general formula (Ib), compounds of general formula (Ib′), compounds of general formula (I), compounds of general formula (I′), and their pharmaceutically acceptable salts, wherein R1, R2, R3, R4, R5, R6, R8, R9, X1, X2, and X3 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds of the disclosure.