公开(公告)号：US20200369657A1

公开(公告)日：2020-11-26

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：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.