WO2024054625A3 - Bifunctional compounds for degrading kras g12d via ubiquitin proteasome pathway - Google Patents

Bifunctional compounds for degrading kras g12d via ubiquitin proteasome pathway Download PDF

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Publication number
WO2024054625A3
WO2024054625A3 PCT/US2023/032284 US2023032284W WO2024054625A3 WO 2024054625 A3 WO2024054625 A3 WO 2024054625A3 US 2023032284 W US2023032284 W US 2023032284W WO 2024054625 A3 WO2024054625 A3 WO 2024054625A3
Authority
WO
WIPO (PCT)
Prior art keywords
kras
degrading
proteasome pathway
ubiquitin proteasome
bifunctional compounds
Prior art date
Application number
PCT/US2023/032284
Other languages
French (fr)
Other versions
WO2024054625A2 (en
Inventor
Yongfeng SUN
Jiping Fu
Haiqiang ZENG
Original Assignee
Nikang Therapeutics, Inc.
Shanghai Blueray Biopharma Co., Ltd.
Nikang Therapeutics (Shanghai) Ltd.
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
Priority claimed from PCT/CN2022/117697 external-priority patent/WO2024050742A1/en
Priority claimed from PCT/CN2023/072897 external-priority patent/WO2024152247A1/en
Application filed by Nikang Therapeutics, Inc., Shanghai Blueray Biopharma Co., Ltd., Nikang Therapeutics (Shanghai) Ltd. filed Critical Nikang Therapeutics, Inc.
Publication of WO2024054625A2 publication Critical patent/WO2024054625A2/en
Publication of WO2024054625A3 publication Critical patent/WO2024054625A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • 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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
    • A61P35/00—Antineoplastic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present disclosure provides certain bifunctional compounds that cause degradation of K- ras G12D via ubiquitin proteasome pathway and are therefore useful for the treatment of diseases mediated by K-ras G12D. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
PCT/US2023/032284 2022-09-08 2023-09-08 Bifunctional compounds for degrading kras g12d via ubiquitin proteasome pathway WO2024054625A2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CNPCT/CN22/117697 2022-09-08
PCT/CN2022/117697 WO2024050742A1 (en) 2022-09-08 2022-09-08 Bifunctional compounds for degrading kras g12d via ubiquitin proteasome pathway
PCT/CN2023/072897 WO2024152247A1 (en) 2023-01-18 Bifunctional compounds for degrading kras g12d via ubiquitin proteasome pathway
CNPCT/CN23/072897 2023-01-18

Publications (2)

Publication Number Publication Date
WO2024054625A2 WO2024054625A2 (en) 2024-03-14
WO2024054625A3 true WO2024054625A3 (en) 2024-04-18

Family

ID=90191765

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2023/032284 WO2024054625A2 (en) 2022-09-08 2023-09-08 Bifunctional compounds for degrading kras g12d via ubiquitin proteasome pathway

Country Status (1)

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WO (1) WO2024054625A2 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019195609A2 (en) * 2018-04-04 2019-10-10 Arvinas Operations, Inc. Modulators of proteolysis and associated methods of use
WO2020142227A1 (en) * 2019-01-03 2020-07-09 The Regents Of The University Of Michigan Estrogen receptor protein degraders
WO2021041671A1 (en) * 2019-08-29 2021-03-04 Mirati Therapeutics, Inc. Kras g12d inhibitors
WO2022173870A1 (en) * 2021-02-09 2022-08-18 Kumquat Biosciences Inc. Heterocyclic compounds and uses thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019195609A2 (en) * 2018-04-04 2019-10-10 Arvinas Operations, Inc. Modulators of proteolysis and associated methods of use
WO2020142227A1 (en) * 2019-01-03 2020-07-09 The Regents Of The University Of Michigan Estrogen receptor protein degraders
WO2021041671A1 (en) * 2019-08-29 2021-03-04 Mirati Therapeutics, Inc. Kras g12d inhibitors
WO2022173870A1 (en) * 2021-02-09 2022-08-18 Kumquat Biosciences Inc. Heterocyclic compounds and uses thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BOND ET AL.: "Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs", ACS CENT. SCI., vol. 6, no. 8, 8 July 2020 (2020-07-08), pages 1367 - 1375, XP055866207, DOI: 10.1021/acscentsci.0c00411 *

Also Published As

Publication number Publication date
WO2024054625A2 (en) 2024-03-14

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