BR112020025274A8 - Compostos antagonistas de pcsk9 - Google Patents

Compostos antagonistas de pcsk9

Info

Publication number
BR112020025274A8
BR112020025274A8 BR112020025274A BR112020025274A BR112020025274A8 BR 112020025274 A8 BR112020025274 A8 BR 112020025274A8 BR 112020025274 A BR112020025274 A BR 112020025274A BR 112020025274 A BR112020025274 A BR 112020025274A BR 112020025274 A8 BR112020025274 A8 BR 112020025274A8
Authority
BR
Brazil
Prior art keywords
compounds
pcsk9
antagonist compounds
pcsk9 antagonist
formula
Prior art date
Application number
BR112020025274A
Other languages
English (en)
Other versions
BR112020025274A2 (pt
Inventor
B Wood Harold
B Josien Hubert
Joseph Tucker Thomas
Dawn Kerekes Angela
Tong Ling
M Walji Abbas
G Nair Anilkumar
Ding Fa-Xiang
Bianchi Elisabetta
Branca Danila
Wu Chengwei
Xiong Yusheng
Nicole Ha Sookhee
Liu Jian
Babu Boga Sobhana
Original Assignee
Merck Sharp & Dohme
Merck Sharp & Dohme Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Sharp & Dohme, Merck Sharp & Dohme Llc filed Critical Merck Sharp & Dohme
Publication of BR112020025274A2 publication Critical patent/BR112020025274A2/pt
Publication of BR112020025274A8 publication Critical patent/BR112020025274A8/pt

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/64Cyclic peptides containing only normal peptide links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/06Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/6454Dibasic site splicing serine proteases, e.g. kexin (3.4.21.61); furin (3.4.21.75) and other proprotein convertases
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21Serine endopeptidases (3.4.21)
    • C12Y304/21061Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • General Chemical & Material Sciences (AREA)
  • Obesity (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Steroid Compounds (AREA)

Abstract

COMPOSTOS ANTAGONISTAS DE PCSK9. São revelados compostos de Fórmula I, (I) ou um sal dos mesmos: onde A, B, D, X, R1, R2 e R8 são como definidos na presente invenção, cujos compostos têm propriedades para antagonizar PCSK9. Descreve-se também formulações farmacêuticas compreendendo os compostos de Fórmula I ou sais do mesmo, e métodos para tratar doenças cardiovasculares e condições relacionadas à atividade de PCSK9, por exemplo, aterosclerose, hipercolesterolemia, doença cardíaca coronária, síndrome metabólica, síndrome coronariana aguda, ou doenças cardiovasculares e condições cardiometabólicas relacionadas.
BR112020025274A 2018-06-21 2019-06-20 Compostos antagonistas de pcsk9 BR112020025274A8 (pt)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862687913P 2018-06-21 2018-06-21
US62/687,913 2018-06-21
PCT/US2019/038155 WO2019246349A1 (en) 2018-06-21 2019-06-20 Pcsk9 antagonist compounds

Publications (2)

Publication Number Publication Date
BR112020025274A2 BR112020025274A2 (pt) 2021-03-09
BR112020025274A8 true BR112020025274A8 (pt) 2023-02-14

Family

ID=67263083

Family Applications (1)

Application Number Title Priority Date Filing Date
BR112020025274A BR112020025274A8 (pt) 2018-06-21 2019-06-20 Compostos antagonistas de pcsk9

Country Status (25)

Country Link
US (2) US11427616B2 (pt)
EP (1) EP3810626A1 (pt)
JP (2) JP7112531B2 (pt)
KR (1) KR20210024035A (pt)
CN (1) CN112313243A (pt)
AR (1) AR115597A1 (pt)
AU (2) AU2019290163C1 (pt)
BR (1) BR112020025274A8 (pt)
CA (1) CA3102629A1 (pt)
CL (2) CL2020003257A1 (pt)
CO (1) CO2021000456A2 (pt)
CR (1) CR20210031A (pt)
DO (1) DOP2020000250A (pt)
EA (1) EA202190086A1 (pt)
EC (1) ECSP21003643A (pt)
GE (1) GEP20237506B (pt)
IL (1) IL279363A (pt)
JO (1) JOP20190150A1 (pt)
MA (1) MA52967A (pt)
MX (1) MX2020013726A (pt)
NI (1) NI202000101A (pt)
PE (1) PE20211584A1 (pt)
PH (1) PH12020552187A1 (pt)
SG (1) SG11202012451WA (pt)
WO (1) WO2019246349A1 (pt)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100558932B1 (ko) * 2005-04-21 2006-03-10 주식회사 엠제이스마트 테크놀러지 다공성 세라믹 분리막 제조방법과, 이에 의해 제조되어진 다공성 세라믹 분리막
DK2968443T3 (da) 2013-03-15 2021-12-06 Protagonist Therapeutics Inc Hepcidinanaloger og anvendelser deraf
WO2015176035A1 (en) 2014-05-16 2015-11-19 Protagonist Therapeutics, Inc. α4β7 INTEGRIN THIOETHER PEPTIDE ANTAGONISTS
EP3169403B1 (en) 2014-07-17 2024-02-14 Protagonist Therapeutics, Inc. Oral peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory bowel diseases
EP3749345A4 (en) 2018-02-08 2022-04-06 Protagonist Therapeutics, Inc. CONJUGATED HEPCIDIN MIMETICS
WO2019246352A1 (en) 2018-06-21 2019-12-26 Merck Sharp & Dohme Corp. Pcsk9 antagonist bicyclo-compounds
US11814445B2 (en) 2018-06-21 2023-11-14 Ra Pharmaceuticals, Inc. Cyclic polypeptides for PCSK9 inhibition
US11814444B2 (en) 2018-06-21 2023-11-14 Ra Pharmaceuticals, Inc. Cyclic polypeptides for PCSK9 inhibition
WO2020009805A2 (en) 2018-06-21 2020-01-09 Merck Sharp & Dohme Corp. Cyclic polypeptides for pcsk9 inhibition
EP3810196A4 (en) 2018-06-21 2022-05-04 Merck Sharp & Dohme Corp. CYCLIC POLYPEPTIDES FOR INHIBITION OF PCSK9
JOP20190150A1 (ar) 2018-06-21 2019-12-21 Merck Sharp & Dohme مركبات مناهضة لـ pcsk9
TW202123960A (zh) * 2019-08-30 2021-07-01 美商默沙東藥廠 Pcsk9拮抗劑化合物
EP4076492A4 (en) * 2019-12-20 2024-01-17 Merck Sharp & Dohme Llc PCSK9 ANTAGONIST COMPOUNDS
WO2021146441A1 (en) 2020-01-15 2021-07-22 Janssen Biotech, Inc. Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases
TW202237167A (zh) 2020-11-20 2022-10-01 比利時商健生藥品公司 介白素-23受體之肽抑制劑組合物
US11932705B2 (en) 2020-12-18 2024-03-19 Merck Sharp & Dohme Llc Cyclic polypeptides for PCSK9 inhibition
AU2022330007A1 (en) * 2021-08-19 2024-02-15 Merck Sharp & Dohme Llc Compounds for treating conditions related to pcsk9 activity
US20230406885A1 (en) 2022-06-15 2023-12-21 Merck Sharp & Dohme Llc Cyclic peptides for trapping interleukin-1 beta

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4393046A (en) 1981-01-30 1983-07-12 Merck & Co., Inc. Combination of thiopeptin and other related sulfur-containing cyclic polypeptide antibiotics with rumen-active diimides to improve ruminant feed efficiency
DE3841520A1 (de) 1988-12-09 1990-06-13 Hoechst Ag Enzymhemmende harnstoffderivate von dipeptiden, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung
US5104869A (en) 1989-10-11 1992-04-14 American Cyanamid Company Renin inhibitors
US5114937A (en) 1989-11-28 1992-05-19 Warner-Lambert Company Renin inhibiting nonpeptides
US5095119A (en) 1990-03-08 1992-03-10 American Home Products Corporation Renin inhibitors
DE69819311T2 (de) 1997-03-07 2004-07-29 Metabasis Therapeutics Inc., San Diego Neue benzimidazol inhibitoren der fructose-1,6-bisphosphatase
WO1998039344A1 (en) 1997-03-07 1998-09-11 Metabasis Therapeutics, Inc. Novel purine inhibitors of fructose-1,6-bisphosphatase
AU6691798A (en) 1997-03-07 1998-09-22 Metabasis Therapeutics, Inc. Novel indole and azaindole inhibitors of fructose-1,6-bisphosphatase
NZ510308A (en) 1998-09-09 2003-06-30 Metabasis Therapeutics Inc Heteroaromatic alkylene substituted phosphonate derivatives useful as inhibitors of Fructose 1,6-bisphosphatase
DE60128475T2 (de) 2000-07-25 2008-02-07 Merck & Co., Inc. N-substituierte indole mit anwendung in der behandlung von diabetes
WO2002060388A2 (en) 2001-01-30 2002-08-08 Merck & Co., Inc. Acyl sulfamides for treatment of obesity, diabetes and lipid disorders
AR040241A1 (es) 2002-06-10 2005-03-23 Merck & Co Inc Inhibidores de la 11-beta-hidroxiesteroide deshidrogrenasa 1 para el tratamiento de la diabetes obesidad y dislipidemia
JP4377815B2 (ja) 2002-08-29 2009-12-02 メルク エンド カムパニー インコーポレーテッド 抗糖尿病活性を有するインドール類
CA2495915A1 (en) 2002-08-29 2004-03-11 Merck & Co., Inc. Indoles having anti-diabetic activity
US7319170B2 (en) 2003-01-17 2008-01-15 Merck & Co., Inc. N-cyclohexylaminocarbonyl benzensulfonmide derivatives
CN101636179B (zh) 2006-11-07 2012-10-10 默沙东公司 Pcsk9拮抗剂
KR101404781B1 (ko) 2007-06-28 2014-06-12 가부시키가이샤 한도오따이 에네루기 켄큐쇼 반도체 장치의 제조 방법
JP2010531307A (ja) 2007-06-28 2010-09-24 メルク フロスト カナダ リミテツド Gpr105活性のアンタゴニストとしての置換縮合ピリミジン
WO2009042053A2 (en) 2007-09-21 2009-04-02 Merck & Co., Inc. Neuromedin u receptor agonists and uses thereof
UY32690A (es) 2009-06-08 2011-01-31 Astrazeneca Ab Péptidos específicos para receptores de melanocortina
WO2011037791A1 (en) 2009-09-25 2011-03-31 Merck Sharp & Dohme Corp. Antagonists of pcsk9
CA2813049A1 (en) 2010-09-23 2012-03-29 The Trustees Of The University Of Pennsylvania Modified compstatin with improved stability and binding properties
MY169485A (en) 2010-12-28 2019-04-15 Cadila Healthcare Ltd Heterocyclic compounds suitable for the treatment of dyslipidemia
EP2721063A4 (en) 2011-06-20 2015-01-14 Hoffmann La Roche PCSK9 BINDING POLYPEPTIDES AND METHOD OF USE THEREOF
PE20150041A1 (es) 2011-10-27 2015-01-28 Massachusetts Inst Technology Derivados de aminoacidos funcionalizados en la terminal n capaces de formar microesferas encapsuladoras de farmaco
WO2013138340A1 (en) 2012-03-13 2013-09-19 Tensive Controls Inc. Melanocortin analogs having enhanced activity and transport
ES2755104T3 (es) 2012-05-17 2020-04-21 Ra Pharmaceuticals Inc Inhibidores peptídicos y peptidomiméticos
BR112015021681A2 (pt) 2013-03-14 2017-11-14 Daiichi Sankyo Co Ltd proteínas de ligação para pcsk9
AU2014237312B2 (en) * 2013-03-15 2019-03-28 Shifa Biomedical Corporation Anti-proprotein convertase subtilisin kexin type 9 (anti-PCSK9) compounds and methods of using the same in the treatment and/or prevention of cardiovascular diseases
WO2016119067A1 (en) 2015-01-30 2016-08-04 Pronasci Inc. Peptides derived from human pcsk9 catalytic domain and uses there of for promoting ldl-r activity
WO2017181061A1 (en) 2016-04-15 2017-10-19 Ra Pharmaceuticals, Inc. Ras binding peptides and methods of use
AU2017281332A1 (en) 2016-06-24 2018-12-20 F. Hoffmann-La Roche Ag Compositions and methods for treating cardiovascular disease
WO2018053517A1 (en) 2016-09-19 2018-03-22 The Texas A&M University System Inhibitors of ldlr-pcsk9 protein-protein interaction and methods of their use
CN107158002B (zh) * 2017-07-01 2020-06-16 维亚生物科技(上海)有限公司 苄撑巴比妥类化合物在作为pcsk9拮抗剂和降低低密度脂蛋白中的应用
WO2019246352A1 (en) 2018-06-21 2019-12-26 Merck Sharp & Dohme Corp. Pcsk9 antagonist bicyclo-compounds
JOP20190150A1 (ar) 2018-06-21 2019-12-21 Merck Sharp & Dohme مركبات مناهضة لـ pcsk9
US11814445B2 (en) 2018-06-21 2023-11-14 Ra Pharmaceuticals, Inc. Cyclic polypeptides for PCSK9 inhibition
US11814444B2 (en) 2018-06-21 2023-11-14 Ra Pharmaceuticals, Inc. Cyclic polypeptides for PCSK9 inhibition
EP3810196A4 (en) 2018-06-21 2022-05-04 Merck Sharp & Dohme Corp. CYCLIC POLYPEPTIDES FOR INHIBITION OF PCSK9
WO2020009805A2 (en) 2018-06-21 2020-01-09 Merck Sharp & Dohme Corp. Cyclic polypeptides for pcsk9 inhibition
TW202123960A (zh) 2019-08-30 2021-07-01 美商默沙東藥廠 Pcsk9拮抗劑化合物

Also Published As

Publication number Publication date
JOP20190150A1 (ar) 2019-12-21
AU2022259744A1 (en) 2022-12-01
MA52967A (fr) 2021-04-28
CL2022000027A1 (es) 2022-08-19
US20230159592A1 (en) 2023-05-25
CO2021000456A2 (es) 2021-01-29
AU2019290163C1 (en) 2022-11-03
CN112313243A (zh) 2021-02-02
BR112020025274A2 (pt) 2021-03-09
SG11202012451WA (en) 2021-01-28
AU2019290163A1 (en) 2021-01-07
IL279363A (en) 2021-01-31
WO2019246349A8 (en) 2021-02-04
DOP2020000250A (es) 2021-02-28
AU2019290163B2 (en) 2022-08-04
JP2021522311A (ja) 2021-08-30
JP2022141879A (ja) 2022-09-29
GEP20237506B (en) 2023-05-25
CA3102629A1 (en) 2019-12-26
NI202000101A (es) 2021-05-28
AR115597A1 (es) 2021-02-03
MX2020013726A (es) 2021-03-02
WO2019246349A1 (en) 2019-12-26
US11427616B2 (en) 2022-08-30
ECSP21003643A (es) 2021-02-26
KR20210024035A (ko) 2021-03-04
JP7112531B2 (ja) 2022-08-03
PE20211584A1 (es) 2021-08-18
CR20210031A (es) 2021-02-11
PH12020552187A1 (en) 2021-07-26
TW202019950A (zh) 2020-06-01
CL2020003257A1 (es) 2021-07-23
US20190389909A1 (en) 2019-12-26
EA202190086A1 (ru) 2021-05-18
EP3810626A1 (en) 2021-04-28

Similar Documents

Publication Publication Date Title
BR112020025274A8 (pt) Compostos antagonistas de pcsk9
BR112014018990A8 (pt) Derivados de ácido benzotiazol-6-il acético e seu uso para tratamento de uma infecção
BR112015021027A8 (pt) compostos terapêuticos, seus usos, e composições farmacêuticas
BR112017024933A8 (pt) Alvocidib produce com a bioavailabilidade aumentada
EA201892207A1 (ru) Индолкарбоксамидные соединения
BR112016016844A2 (pt) Compostos heterocíclicos
BR112017022544A2 (pt) ?composto, composição, e, método para tratamento de infecção por hiv?.
BRPI0818533B8 (pt) composto, composição farmacêutica, uso de um composto, e, processo para a preparação de um composto
BR112017023740A2 (pt) ?forma sólida de um composto, processo para a preparação de uma forma sólida, composição farmacêutica, método para o tratamento ou prevenção de doenças e utilização de uma forma sólida?
BR112019000589A2 (pt) pirimidina carboxamidas como inibidores da enzima vanina-1
BR112016030730A8 (pt) composto
BR112018002689A2 (pt) composto, composição útil e método para tratamento de infecção por hiv
BR112018070536A2 (pt) composto, composição farmacêutica, combinação, uso de um composto ou um sal farmaceuticamente aceitável do mesmo, e, método de tratamento de uma doença ou condição
BR112018006545A2 (pt) ?composto, composição farmacêutica, combinação, uso de um composto, e, método para tratamento de uma doença ou condição?
BR112019000897A2 (pt) sal de adição de ácido, composição farmacêutica, uso do sal de adição de ácido ou da composição farmacêutica, e, método para prevenção, tratamento ou atenuação de um distúrbio de fibrose de tecido ou órgão.
BR112018013033A2 (pt) compostos de indolinonas e seu uso no tratamentod de doenças fibróticas
EA201890532A1 (ru) Новые аннелированные бензамиды
BR112014029439A2 (pt) derivados de ácido salicílico, sal farmaceuticamente aceitável dos mesmos, composição dos mesmos e método de uso dos mesmos
BR112022000782A2 (pt) Composto, composição farmacêutica, processo para preparar um composto, composto intermediário, e, uso de um composto, ou de um sal farmaceuticamente aceitável ou solvato do mesmo, ou de uma composição farmacêutica
BR112022006572A2 (pt) Inibidores orais do fator d do complemento
CL2021001968A1 (es) Sales de sulcardina
BR112018070514A2 (pt) composto, composição farmacêutica, combinação, uso de um composto ou um sal farmaceuticamente aceitável do mesmo, e, método de tratamento de uma doença ou condição
BR112022005706A2 (pt) Inibidores de 1,6-naftiridina substituída de cdk5
BR112019007631A2 (pt) inibidores de bromodomínios
BR112018003181A2 (pt) composto, composição, e, método para tratar infecção por hiv

Legal Events

Date Code Title Description
B350 Update of information on the portal [chapter 15.35 patent gazette]
B25F Entry of change of name and/or headquarter and transfer of application, patent and certif. of addition of invention: change of name on requirement

Owner name: MERCK SHARP AND DOHME CORP. (US)

Free format text: A FIM DE ATENDER A ALTERACAO DE NOME REQUERIDA ATRAVES DA PETICAO NO 870220065319, DE 25/07/2022, E NECESSARIO COMPLEMENTAR O VALOR DA GUIA DE RECOLHIMENTO, VISTO QUE TRATA-SE DE UMA TRANSFERENCIA POR INCORPORACAO E NAO DE UMA ALTERACAO DE NOME. ALEM DISSO, E PRECISO APRESENTAR A GUIA DE CUMPRIMENTO DE EXIGENCIA.

B25A Requested transfer of rights approved

Owner name: MERCK SHARP AND DOHME LLC (US)

B25E Requested change of name of applicant rejected

Owner name: MERCK SHARP AND DOHME LLC (US)

Free format text: INDEFERIDO O PEDIDO DE ALTERACAO DE NOME CONTIDO NA PETICAO 870220065319 DE 25/07/2022, EM VIRTUDE DE NAO SE TRATAR DE UMA ALTERACAO DE NOME E SIM DE UMA TRANSFERENCIA DE TITULAR QUE JA FOI PUBLICADA.