WO2024259310A3 - Passive permeable pcsk9 antagonist compounds - Google Patents

Passive permeable pcsk9 antagonist compounds Download PDF

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Publication number
WO2024259310A3
WO2024259310A3 PCT/US2024/034113 US2024034113W WO2024259310A3 WO 2024259310 A3 WO2024259310 A3 WO 2024259310A3 US 2024034113 W US2024034113 W US 2024034113W WO 2024259310 A3 WO2024259310 A3 WO 2024259310A3
Authority
WO
WIPO (PCT)
Prior art keywords
compounds
passive
permeable
antagonist compounds
pcsk9
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2024/034113
Other languages
French (fr)
Other versions
WO2024259310A2 (en
Inventor
Abbas M. Walji
Harold B. Wood
Yuhua Huang
Thomas Joseph Tucker
Yi-Heng Chen
Mark W. Embrey
Fa-Xiang Ding
Jennifer HANISAK
Charles Lee Jayne
Chengwei WU
Jennifer Marie JOHNSTON
Shawn P. Walsh
Zhongxiang Sun
Danila Branca
Stefania Colarusso
Anilkumar G. Nair
Michael Man-Chu Lo
Peter Orth
Sookhee Nicole Ha
Liangqin Guo
Ling Tong
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Sharp and Dohme LLC
Original Assignee
Merck Sharp and 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 and Dohme LLC filed Critical Merck Sharp and Dohme LLC
Priority to EP24824271.1A priority Critical patent/EP4727552A2/en
Publication of WO2024259310A2 publication Critical patent/WO2024259310A2/en
Publication of WO2024259310A3 publication Critical patent/WO2024259310A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains four or more hetero rings
    • 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
    • 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
    • C07D498/22—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 four or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Obesity (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Compounds of Formula (I), or a pharmaceutically acceptable salt thereof are disclosed (I), where A, B, R1, R2, R3, R4 and R5 are as defined herein. These compounds are antagonists of PCSK9 and have high passive (or intrinsic) permeability such that may be used without a permeability enhancing agent. Also described are pharmaceutical compositions comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g., atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.
PCT/US2024/034113 2023-06-15 2024-06-14 Passive permeable pcsk9 antagonist compounds Ceased WO2024259310A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP24824271.1A EP4727552A2 (en) 2023-06-15 2024-06-14 Passive permeable pcsk9 antagonist compounds

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202363508454P 2023-06-15 2023-06-15
US63/508,454 2023-06-15
US202363517742P 2023-08-04 2023-08-04
US63/517,742 2023-08-04

Publications (2)

Publication Number Publication Date
WO2024259310A2 WO2024259310A2 (en) 2024-12-19
WO2024259310A3 true WO2024259310A3 (en) 2025-01-16

Family

ID=93852845

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/034113 Ceased WO2024259310A2 (en) 2023-06-15 2024-06-14 Passive permeable pcsk9 antagonist compounds

Country Status (2)

Country Link
EP (1) EP4727552A2 (en)
WO (1) WO2024259310A2 (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019246387A1 (en) * 2018-06-21 2019-12-26 Ra Pharmaceuticals, Inc. Cyclic peptides for pcsk9 inhibition
WO2019246352A1 (en) * 2018-06-21 2019-12-26 Merck Sharp & Dohme Corp. Pcsk9 antagonist bicyclo-compounds
WO2019246349A1 (en) * 2018-06-21 2019-12-26 Merck Sharp & Dohme Corp. Pcsk9 antagonist compounds

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019246387A1 (en) * 2018-06-21 2019-12-26 Ra Pharmaceuticals, Inc. Cyclic peptides for pcsk9 inhibition
WO2019246352A1 (en) * 2018-06-21 2019-12-26 Merck Sharp & Dohme Corp. Pcsk9 antagonist bicyclo-compounds
WO2019246349A1 (en) * 2018-06-21 2019-12-26 Merck Sharp & Dohme Corp. Pcsk9 antagonist compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ZHANG ET AL.: "Identification of a Small Peptide That Inhibits PCSK9 Protein Binding to the Low Density Lipoprotein Receptor", THE JOURNAL OF BIOLOGICAL CHEMISTRY ., vol. 289, no. 2, 2014, pages 942 - 955, XP055546006, DOI: 10.1074/jbc.M113.514067 *

Also Published As

Publication number Publication date
EP4727552A2 (en) 2026-04-22
WO2024259310A2 (en) 2024-12-19

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