CN113166114B - 作为蛋白质原转换酶枯草杆菌蛋白酶/kexin9型（pcsk9）抑制剂的用于治疗代谢障碍的环状四聚体化合物 - Google Patents

作为蛋白质原转换酶枯草杆菌蛋白酶/kexin9型（pcsk9）抑制剂的用于治疗代谢障碍的环状四聚体化合物 Download PDF

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CN113166114B
CN113166114B CN201980076002.XA CN201980076002A CN113166114B CN 113166114 B CN113166114 B CN 113166114B CN 201980076002 A CN201980076002 A CN 201980076002A CN 113166114 B CN113166114 B CN 113166114B
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methyl
chlorobenzyl
imidazol
chloro
phenoxy
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CN113166114A (zh
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K·布林纳
B·A·德克里斯托弗
A·N·弗莱尔
A·A·戈洛索夫
P·格罗舍
E·Y·刘
J·Y·C·毛
L·G·莫诺维奇
T·J·帕特尔
C·C·桑切斯
苏连胜
杨莉华
郑锐
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Novartis AG
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    • 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
    • C07D471/08—Bridged systems
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
    • C07D211/56—Nitrogen atoms
    • 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
    • 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
    • C07D498/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/12—Cyclic peptides with only normal peptide bonds in the ring
    • C07K5/126—Tetrapeptides

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Obesity (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Hydrogenated Pyridines (AREA)
CN201980076002.XA 2018-11-27 2019-11-26 作为蛋白质原转换酶枯草杆菌蛋白酶/kexin9型（pcsk9）抑制剂的用于治疗代谢障碍的环状四聚体化合物 Active CN113166114B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201862772030P 2018-11-27 2018-11-27
US62/772,030 2018-11-27
US201962924828P 2019-10-23 2019-10-23
US62/924,828 2019-10-23
PCT/IB2019/060201 WO2020110009A1 (en) 2018-11-27 2019-11-26 Cyclic tetramer compounds as proprotein convertase subtilisin/kexin type 9 (pcsk9) inhibitors for the treatment of metabolic disorders

Publications (2)

Publication Number Publication Date
CN113166114A CN113166114A (zh) 2021-07-23
CN113166114B true CN113166114B (zh) 2025-01-03

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US (2) US11026993B2 (https=)
EP (1) EP3887365A1 (https=)
JP (1) JP7577656B2 (https=)
KR (1) KR20210096154A (https=)
CN (1) CN113166114B (https=)
AU (1) AU2019387294B2 (https=)
BR (1) BR112021009857A2 (https=)
CA (1) CA3115960A1 (https=)
CL (1) CL2021001365A1 (https=)
CO (1) CO2021006895A2 (https=)
CR (1) CR20210267A (https=)
CU (1) CU20210043A7 (https=)
DO (1) DOP2021000100A (https=)
EC (1) ECSP21036194A (https=)
IL (1) IL283374A (https=)
JO (1) JOP20210120A1 (https=)
MA (1) MA54284A (https=)
MX (1) MX2021006069A (https=)
PE (1) PE20211658A1 (https=)
PH (1) PH12021551049A1 (https=)
PY (1) PY1998404A (https=)
SG (1) SG11202103807WA (https=)
TW (1) TW202038990A (https=)
UY (1) UY38485A (https=)
WO (1) WO2020110009A1 (https=)

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US11882610B2 (en) * 2020-08-13 2024-01-23 Qualcomm Incorporated Establishing connections using multiple subscriber identity modules via a single communication link
CN114163343A (zh) * 2021-12-10 2022-03-11 许昌学院 含氟氨基酸及衍生物含氟多肽的制备方法以及应用

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CN108239073A (zh) * 2016-12-23 2018-07-03 财团法人生物技术开发中心 化合物、医药组成物及其用途

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JOP20210120A1 (ar) 2021-05-26
CL2021001365A1 (es) 2022-01-14
BR112021009857A2 (pt) 2021-08-17
ECSP21036194A (es) 2021-06-30
US20210252103A1 (en) 2021-08-19
MA54284A (fr) 2022-03-02
TW202038990A (zh) 2020-11-01
CO2021006895A2 (es) 2021-06-10
US20200164024A1 (en) 2020-05-28
JP7577656B2 (ja) 2024-11-05
WO2020110009A1 (en) 2020-06-04
PY1998404A (es) 2021-06-17
SG11202103807WA (en) 2021-06-29
CA3115960A1 (en) 2020-06-04
UY38485A (es) 2020-06-30
US11026993B2 (en) 2021-06-08
DOP2021000100A (es) 2021-06-30
MX2021006069A (es) 2021-07-06
PE20211658A1 (es) 2021-08-24
CN113166114A (zh) 2021-07-23
CU20210043A7 (es) 2022-01-13
JP2022507957A (ja) 2022-01-18
AU2019387294A1 (en) 2021-05-13
CR20210267A (es) 2021-08-16
AU2019387294B2 (en) 2022-09-08
KR20210096154A (ko) 2021-08-04
US11813306B2 (en) 2023-11-14
IL283374A (en) 2021-07-29
PH12021551049A1 (en) 2021-12-06
EP3887365A1 (en) 2021-10-06

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