EA202191890A1 - Ингибиторы pcsk9 и способы их применения - Google Patents

Ингибиторы pcsk9 и способы их применения

Info

Publication number
EA202191890A1
EA202191890A1 EA202191890A EA202191890A EA202191890A1 EA 202191890 A1 EA202191890 A1 EA 202191890A1 EA 202191890 A EA202191890 A EA 202191890A EA 202191890 A EA202191890 A EA 202191890A EA 202191890 A1 EA202191890 A1 EA 202191890A1
Authority
EA
Eurasian Patent Office
Prior art keywords
methods
pcsk9 inhibitors
pcsk9
inhibitors
bind
Prior art date
Application number
EA202191890A
Other languages
English (en)
Inventor
Майкл Х. Серрано-Ву
Брайн К. Хаббард
Вирендар Каушик
Даг Даниелс
Original Assignee
Астразенека Аб
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 Астразенека Аб filed Critical Астразенека Аб
Publication of EA202191890A1 publication Critical patent/EA202191890A1/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D235/30—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
    • C07D253/06—1,2,4-Triazines
    • C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
    • C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D253/075—Two hetero atoms, in positions 3 and 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • C07D271/07—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Настоящее изобретение относится к новому фармакофорному ингибитору PCSK9 и к гетероарильным соединениям, которые связывают белок PCSK9.
EA202191890A 2019-01-18 2020-01-16 Ингибиторы pcsk9 и способы их применения EA202191890A1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201962794239P 2019-01-18 2019-01-18
PCT/US2020/013882 WO2020150474A1 (en) 2019-01-18 2020-01-16 Pcsk9 inhibitors and methods of use thereof

Publications (1)

Publication Number Publication Date
EA202191890A1 true EA202191890A1 (ru) 2022-02-03

Family

ID=71608564

Family Applications (1)

Application Number Title Priority Date Filing Date
EA202191890A EA202191890A1 (ru) 2019-01-18 2020-01-16 Ингибиторы pcsk9 и способы их применения

Country Status (15)

Country Link
US (2) US11603523B2 (ru)
EP (1) EP3911640A4 (ru)
JP (1) JP2022518016A (ru)
KR (1) KR20210116549A (ru)
CN (1) CN113412258A (ru)
AU (2) AU2020209216A1 (ru)
BR (1) BR112021013924A2 (ru)
CA (1) CA3125767A1 (ru)
EA (1) EA202191890A1 (ru)
IL (1) IL284661A (ru)
MA (1) MA54758A (ru)
MX (1) MX2021008661A (ru)
SG (1) SG11202107615TA (ru)
TW (1) TW202042817A (ru)
WO (1) WO2020150474A1 (ru)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3125765A1 (en) * 2019-01-18 2020-07-23 Astrazeneca Ab Pcsk9 inhibitors and methods of use thereof
CN113248501B (zh) * 2021-06-17 2021-10-08 南京韦尔优众医药有限公司 Cly系列化合物及其制备方法和制备药物的用途
CN113735846A (zh) * 2021-10-11 2021-12-03 河北师范大学 一种苯并噻唑衍生物及其医药用途
TW202333563A (zh) * 2021-11-12 2023-09-01 瑞士商諾華公司 用於治療疾病或障礙之二胺基環戊基吡啶衍生物
WO2024062089A1 (en) 2022-09-23 2024-03-28 Astrazeneca Ab Pcsk9 inhibitors and methods of use thereof
WO2024062090A1 (en) 2022-09-23 2024-03-28 Astrazeneca Ab Pcsk9 inhibitors and methods of use thereof
WO2024078620A1 (zh) * 2022-10-14 2024-04-18 上海翰森生物医药科技有限公司 含氮杂环类衍生物抑制剂、其制备方法和应用

Family Cites Families (72)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995035287A1 (en) 1994-06-17 1995-12-28 F.Hoffmann-La Roche Ag N,n'-bis(quinolin-4-yl)-diamine derivatives, their preparation and their use as antimalarials
WO1996018616A1 (en) 1994-12-12 1996-06-20 Merck & Co., Inc. Substituted 2-aminopyridines as inhibitors of nitric oxide synthase
SE9603285D0 (sv) 1996-09-10 1996-09-10 Astra Ab New compounds
US5874438A (en) 1996-10-11 1999-02-23 Bayer Aktiengesellschaft 2,2'-bridged bis-2,4-diaminoquinazolines
US20040138284A1 (en) 2000-02-11 2004-07-15 Matthias Wiesner Indol-3-yl derivatives
GB0014022D0 (en) 2000-06-08 2000-08-02 Novartis Ag Organic compounds
US7179912B2 (en) 2000-09-01 2007-02-20 Icos Corporation Materials and methods to potentiate cancer treatment
EP1217000A1 (en) 2000-12-23 2002-06-26 Aventis Pharma Deutschland GmbH Inhibitors of factor Xa and factor VIIa
RU2345993C2 (ru) 2001-09-21 2009-02-10 Бристол-Маерс Сквибб Компани ЛАКТАМСОДЕРЖАЩЕЕ СОЕДИНЕНИЕ И ЕГО ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА Xa
CA2474239A1 (en) 2002-01-18 2003-07-24 Pharmacia Corporation Substituted pyridazinones as inhibitors of p38
WO2003099276A1 (en) 2002-05-10 2003-12-04 Bristol-Myers Squibb Company 1,1-disubstituted cycloalkyl derivatives as factor xa inhibitors
US20040087590A1 (en) 2002-08-23 2004-05-06 University Of Connecticut Novel biphenyl and biphenyl-like cannabinoids
US20050197350A1 (en) 2003-03-31 2005-09-08 Taisho Pharmaceutical Co., Ltd. Novel quinoline, tetrahydroquinazoline, and pyrimidine derivatives and methods of treatment related to the use thereof
BRPI0409609A (pt) 2003-04-22 2006-04-18 Avanir Pharmaceuticals mediadores do transporte reverso de colesterol para o tratamento da hipercolesterolemia
UY28953A1 (es) * 2004-06-09 2006-01-31 Avanir Pharmaceuticals Derivados heterocíclicos para el tratamiento de hiperlipidemia y enfermedades relacionadas
EP1814551A2 (en) 2004-09-20 2007-08-08 Xenon Pharmaceuticals Inc. Pyridazine derivatives for inhibiting human stearoyl-coa-desaturase
WO2006035967A1 (en) 2004-09-30 2006-04-06 Taisho Pharmaceutical Co., Ltd. Pyridine derivatives and their use as medicaments for treating diseases related to mch receptor
US7381732B2 (en) 2004-10-26 2008-06-03 Bristol-Myers Squibb Company Pyrazolobenzamides and derivatives as factor Xa inhibitors
CA2585490A1 (en) 2004-11-12 2006-05-18 Galapagos Nv Nitrogen heteroaromatic compounds which bind to the active site of protein kinase enzymes
GB0428082D0 (en) 2004-12-22 2005-01-26 Welcome Trust The Ltd Therapeutic compounds
WO2006126081A2 (en) * 2005-05-24 2006-11-30 Pharmacia & Upjohn Company Llc Pyridino [2 , 3-b] pyrazinones as pde-5 inhibitors
EP1890703B1 (en) 2005-06-14 2016-05-11 Taigen Biotechnology Pyrimidine compounds as chemokine receptors inhibitors
US20070203236A1 (en) 2006-01-11 2007-08-30 Smith Jeffrey W Novel antagonists of the human fatty acid synthase thioesterase
JP2007291087A (ja) 2006-03-29 2007-11-08 Taisho Pharmaceut Co Ltd ピリジン誘導体及びその使用に関連する治療法
PL2069312T3 (pl) 2006-07-25 2013-03-29 Cephalon Inc Pochodne pirydazynonu
WO2008046216A1 (en) 2006-10-18 2008-04-24 Methylgene, Inc. Kinase inhibitors and uses thereof
WO2008061796A2 (en) 2006-11-24 2008-05-29 Ac Immune Sa Compounds for the treatment of diseases associated with amyloid or amyloid-like proteins
WO2008072963A1 (en) 2006-12-13 2008-06-19 Givaudan Nederland Services B.V. Flavour modulating derivative of a carboxylic acid and a purine, pyrimidine, nucleoside or nucleotide
CA2703712A1 (en) * 2007-10-26 2009-04-30 Joseph A. Hedrick Anti-pcsk9 and methods for treating lipid and cholesterol disorders
CA2726588C (en) 2008-06-03 2019-04-16 Karl Kossen Compounds and methods for treating inflammatory and fibrotic disorders
WO2010048149A2 (en) 2008-10-20 2010-04-29 Kalypsys, Inc. Heterocyclic modulators of gpr119 for treatment of disease
CN102596946B (zh) 2009-08-05 2015-06-17 港大科桥有限公司 抗病毒化合物及其制备和使用方法
WO2011147199A1 (en) 2010-05-28 2011-12-01 Versitech Limited Compounds and methods for treating viral infections
AU2011259929B2 (en) 2010-06-04 2014-07-31 Kowa Company, Ltd. Optically active dibenzylamine derivative, and manufacturing method for same
US9050334B2 (en) 2010-07-16 2015-06-09 Innov88 Llc MIF inhibitors and their uses
WO2012016133A2 (en) 2010-07-29 2012-02-02 President And Fellows Of Harvard College Ros1 kinase inhibitors for the treatment of glioblastoma and other p53-deficient cancers
WO2012088438A1 (en) 2010-12-22 2012-06-28 Eutropics Pharmaceuticals, Inc. Compositions and methods useful for treating diseases
EP2668162A1 (en) 2011-01-28 2013-12-04 Novartis AG Substituted bi-heteroaryl compounds as cdk9 inhibitors and their uses
EP2696682B1 (en) 2011-04-13 2018-03-21 Innovimmune Biotherapeutics, Inc. Mif inhibitors and their uses
CA2837312A1 (en) 2011-05-26 2012-11-29 Sunovion Pharmaceuticals Inc. Metabotropic glutamate receptor 5 allosteric modulators and methods of use thereof
JP5741850B2 (ja) 2011-09-13 2015-07-01 コニカミノルタ株式会社 光学フィルム、それを含む偏光板および液晶表示装置
JPWO2013137371A1 (ja) 2012-03-15 2015-08-03 興和株式会社 新規ピリミジン化合物及びそれらを含有する医薬
CN107243078A (zh) 2012-05-25 2017-10-13 克塔巴西斯制药有限公司 使前蛋白转化酶枯草溶菌素/kexin 9型（pcsk9）减少的方法
KR102057877B1 (ko) 2012-07-18 2019-12-20 노스 앤드 사우스 브라더 파마시 인베스트먼트 컴파니 리미티드 질소함유 헤테로고리 유도체 및 그의 약물에서의 용도
TWI644899B (zh) 2013-02-04 2018-12-21 健生藥品公司 Ｆｌａｐ調節劑
CA2899954A1 (en) 2013-02-04 2014-08-07 Merck Patent Gmbh Positive allosteric modulators of mglur3
LT2970218T (lt) 2013-03-12 2019-03-12 Vertex Pharmaceuticals Incorporated Dna-pk inhibitoriai
EP2986599A1 (en) * 2013-04-17 2016-02-24 Pfizer Inc. N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases
US9212182B2 (en) 2013-06-12 2015-12-15 Amgen Inc. Bicyclic sulfonamide compounds as sodium channel inhibitors
AR092240A1 (es) 2013-08-26 2015-04-08 Sunshine Lake Pharma Co Ltd Derivados heterociclicos nitrogenados y su aplicacion en farmacos
CN104558685B (zh) 2013-10-24 2017-09-29 中国石油化工股份有限公司 一种磷氮膨胀型阻燃剂及其合成方法
EP3148537B1 (en) 2014-05-30 2018-09-26 Université Paris Descartes Cyclic compounds having a 1,3 diamino-functionality for use in the treatment of hiv infection
TWI744723B (zh) 2014-06-20 2021-11-01 美商基利科學股份有限公司 多環型胺甲醯基吡啶酮化合物之合成
AR102094A1 (es) 2014-09-25 2017-02-01 Araxes Pharma Llc Inhibidores de proteínas kras con una mutación g12c
WO2016054388A1 (en) 2014-10-03 2016-04-07 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Glutaminase inhibitors
JP6771469B2 (ja) 2015-01-20 2020-10-21 ベーリンガー インゲルハイム アニマル ヘルス ユーエスエイ インコーポレイテッド 駆虫性化合物、組成物及びこれらの使用方法
CA3010327A1 (en) 2016-01-20 2017-07-27 Janssen Sciences Ireland Uc Aryl substituted pyrimidines for use in influenza virus infection
DK3429591T3 (da) 2016-03-16 2023-06-19 Kura Oncology Inc Substituerede thieno[2,3-D]pyrimidin-derivater som inhibitorer af Menin-MLL og fremgangsmåder til anvendelse
TW201808888A (zh) 2016-05-05 2018-03-16 嘉來克生命科學有限責任公司 整合應激途徑之調節劑
WO2018106818A1 (en) 2016-12-07 2018-06-14 Kura Oncology, Inc. Methods of promoting beta cell proliferation
WO2018106820A1 (en) 2016-12-07 2018-06-14 Kura Oncology, Inc. Methods of promoting beta cell proliferation
WO2018165718A1 (en) 2017-03-17 2018-09-20 Cardio Therapeutics Pty Ltd Heterocyclic inhibitors of pcsk9
JP2020514388A (ja) 2017-03-24 2020-05-21 クラ オンコロジー，インク． 血液悪性腫瘍およびユーイング肉腫を処置するための方法
AU2018282747B2 (en) 2017-06-14 2024-01-18 Trevena, Inc. Compounds for modulating S1P1 activity and methods of using the same
CN109384712B (zh) 2017-08-14 2021-05-07 北京宽厚医药科技有限公司 靶向nk1受体拮抗剂及其在化疗所致恶心、呕吐治疗中的应用
WO2019079701A1 (en) 2017-10-20 2019-04-25 Dana-Farber Cancer Institute, Inc. HETEROBIFUNCTIONAL COMPOUNDS HAVING IMPROVED SPECIFICITY FOR BRD4 BROMODOMAINE
UY37957A (es) 2017-11-02 2019-05-31 Abbvie Inc Moduladores de la vía de estrés integrada
WO2019111225A1 (en) 2017-12-08 2019-06-13 Avaliv Therapeutics Compounds and methods for the treatment of non‑alcoholic steatohepatitis
IL276082B2 (en) 2018-01-17 2024-01-01 Vertex Pharma DNA-PK inhibitor compounds, preparations containing them and their uses
AU2019257651B2 (en) 2018-04-24 2023-05-25 Vertex Pharmaceuticals Incorporated Pteridinone compounds and uses thereof
US20190374526A1 (en) 2018-06-06 2019-12-12 Merck Sharp & Dohme Corp. Substituted Heterocyclic Compounds as Inhibitors of PRDM9
CA3125765A1 (en) 2019-01-18 2020-07-23 Astrazeneca Ab Pcsk9 inhibitors and methods of use thereof

Also Published As

Publication number Publication date
AU2020209216A1 (en) 2021-08-26
MA54758A (fr) 2022-04-27
IL284661A (en) 2021-08-31
JP2022518016A (ja) 2022-03-11
CA3125767A1 (en) 2020-07-23
BR112021013924A2 (pt) 2021-09-21
US20230407285A1 (en) 2023-12-21
US20200231584A1 (en) 2020-07-23
KR20210116549A (ko) 2021-09-27
EP3911640A4 (en) 2022-10-26
TW202042817A (zh) 2020-12-01
AU2023201972A1 (en) 2023-05-04
EP3911640A1 (en) 2021-11-24
SG11202107615TA (en) 2021-08-30
CN113412258A (zh) 2021-09-17
US11603523B2 (en) 2023-03-14
MX2021008661A (es) 2021-08-19
WO2020150474A1 (en) 2020-07-23

Similar Documents

Publication Publication Date Title
EA202191890A1 (ru) Ингибиторы pcsk9 и способы их применения
EA202091186A1 (ru) ИНГИБИТОРЫ KRas G12C
BR112021024224A2 (pt) Inibidores de tead e usos dos mesmos
EA201490265A1 (ru) Ингибиторы тирозинкиназы брутона
EA201891024A1 (ru) Соединения-ингибиторы tank-связывающей киназы
EA202191892A1 (ru) Ингибиторы pcsk9 и способы их применения
EA201270553A1 (ru) Ингибиторы тирозинкиназы брутона
EA200901313A1 (ru) Ингибиторы тирозинкиназы брутона
EA201690764A1 (ru) Ингибитор грелин-o-ацилтрансферазы
EA202092263A1 (ru) Аминопиридиновые производные в качестве ингибиторов ctps1
EA202092317A1 (ru) Ингибитор белок-белковых взаимодействий фенилтриазольных соединений mll1-wdr5
EA201992137A1 (ru) ПИРИМИДОПИРИМИДИНОНЫ В КАЧЕСТВЕ ИНГИБИТОРОВ КИНАЗЫ Wee-1
MA38828A1 (fr) Anticorps dirigés contre l'inhibiteur des activateurs du plasminogène de type 1 (pai-1) et leurs utilisations
CL2021002656A1 (es) Compuestos de pirrolotriazina, inhibidores selectivos de proteínas quinasas kit y pdgfralfa; composición y uso.
EA202192575A1 (ru) Соединения dbait в сочетании с ингибиторами киназ для лечения рака
EA202090119A1 (ru) Аморфные и кристаллические формы ido-ингибиторов
EA201892051A1 (ru) Фармацевтические композиции для лечения злокачественного новообразования
EA201792247A1 (ru) Ингибиторы деацетилаз гистонов и композиции и способы их применения
EA201890364A1 (ru) СОЕДИНЕНИЯ, ПРИГОДНЫЕ ДЛЯ ИНГИБИРОВАНИЯ ROR-ГАММА-t
EA201790484A1 (ru) Производные тетрагидрохинолина в качестве ингибиторов бромодомена
EA201992302A1 (ru) Соединения, используемые в качестве ингибиторов alcat1
CO2022001860A2 (es) Derivados quinolina como inhibidores de proteína quinasa
EA201892045A1 (ru) ПРОИЗВОДНЫЕ α-ТРУКСИЛЛОВОЙ КИСЛОТЫ И ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ С НИМИ
EA202190989A1 (ru) Новый способ синтеза производных пиперазинил-этокси-бромфенила и их применение в получении содержащих их соединений
EA201590729A1 (ru) Производные 3,4-дизамещенного оксазолидинона и их применение в качестве ингибиторов кальцийактивируемых калиевых каналов