CA3154942A1 - Small molecule degraders of helios and methods of use - Google Patents

Small molecule degraders of helios and methods of use Download PDF

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Publication number
CA3154942A1
CA3154942A1 CA3154942A CA3154942A CA3154942A1 CA 3154942 A1 CA3154942 A1 CA 3154942A1 CA 3154942 A CA3154942 A CA 3154942A CA 3154942 A CA3154942 A CA 3154942A CA 3154942 A1 CA3154942 A1 CA 3154942A1
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CA
Canada
Prior art keywords
group
aryl
alkyl
cycloalkyl
heteroaryl
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Pending
Application number
CA3154942A
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English (en)
French (fr)
Inventor
Nathanael S. Gray
Hu Liu
Tinghu Zhang
Lyn Howard Jones
Jianwei Che
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Dana Farber Cancer Institute Inc
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Individual
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Publication of CA3154942A1 publication Critical patent/CA3154942A1/en
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    • 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
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07D419/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms
    • C07D419/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms 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
    • 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
    • C07D487/08—Bridged 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
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-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
    • 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
    • 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
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
CA3154942A 2019-10-30 2020-10-29 Small molecule degraders of helios and methods of use Pending CA3154942A1 (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201962928139P 2019-10-30 2019-10-30
US62/928,139 2019-10-30
US202063035272P 2020-06-05 2020-06-05
US63/035,272 2020-06-05
US202063047411P 2020-07-02 2020-07-02
US63/047,411 2020-07-02
PCT/US2020/057930 WO2021087093A1 (en) 2019-10-30 2020-10-29 Small molecule degraders of helios and methods of use

Publications (1)

Publication Number Publication Date
CA3154942A1 true CA3154942A1 (en) 2021-05-06

Family

ID=75715607

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3154942A Pending CA3154942A1 (en) 2019-10-30 2020-10-29 Small molecule degraders of helios and methods of use

Country Status (16)

Country Link
US (1) US20230002397A1 (https=)
EP (1) EP4051386A4 (https=)
JP (1) JP7720833B2 (https=)
KR (1) KR20220092920A (https=)
CN (1) CN114650868A (https=)
AU (1) AU2020374957A1 (https=)
BR (1) BR112022007867A2 (https=)
CA (1) CA3154942A1 (https=)
CL (1) CL2022001111A1 (https=)
CR (1) CR20220234A (https=)
DO (1) DOP2022000091A (https=)
IL (1) IL292173A (https=)
MX (1) MX2022005232A (https=)
PE (1) PE20221457A1 (https=)
PH (1) PH12022550980A1 (https=)
WO (1) WO2021087093A1 (https=)

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* Cited by examiner, † Cited by third party
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CR20220234A (es) * 2019-10-30 2022-07-19 Dana Farber Cancer Inst Inc Degradadores de moléculas pequeñas de helios y procedimientos de uso
AU2020387392B2 (en) 2019-11-19 2025-09-11 Bristol-Myers Squibb Company Compounds useful as inhibitors of Helios protein
US20230271940A1 (en) * 2020-08-03 2023-08-31 Novartis Ag Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
IL301690A (en) * 2020-10-16 2023-05-01 Dana Farber Cancer Inst Inc Piperidinyl small molecule degraders of helios and methods of use
EP4452415B1 (en) 2021-12-22 2026-02-25 Gilead Sciences, Inc. Ikaros zinc finger family degraders and uses thereof
CN118401512A (zh) * 2021-12-24 2024-07-26 苏州开拓药业股份有限公司 一种具有酰亚胺骨架的多蛋白降解剂
CN116640122A (zh) * 2022-02-16 2023-08-25 苏州国匡医药科技有限公司 Ikzf2降解剂及包含其的药物组合物和用途
CA3253296A1 (en) 2022-03-17 2023-09-21 Gilead Sciences, Inc. Zinc Finger Degradation Agents of the Ikaros Family and Their Uses
WO2023183540A1 (en) * 2022-03-25 2023-09-28 Regents Of The University Of Michigan Ikzf2 degraders and uses thereof
WO2023201012A1 (en) * 2022-04-15 2023-10-19 Regents Of The University Of Michigan Ikzf2 degraders and uses thereof
CN119013270A (zh) * 2022-04-29 2024-11-22 西藏海思科制药有限公司 一种含氮杂环衍生物及其组合物和药学上的应用
EP4570792A1 (en) * 2022-08-10 2025-06-18 Gluetacs Therapeutics (Shanghai) Co., Ltd. Compound based on isoindoline-substituted glutarimide backbone and use thereof
WO2024073871A1 (en) * 2022-10-04 2024-04-11 Biofront Ltd Gspt1 degraders, compositions comprising the degrader, and methods of using the same
JP2025537123A (ja) * 2022-11-11 2025-11-14 ニカング セラピューティクス， インコーポレイテッド ユビキチンプロテアソーム経路を介してサイクリン依存性キナーゼ２を分解するための２，５－置換ピリミジン誘導体を含有する二官能性化合物
WO2024109918A1 (zh) * 2022-11-24 2024-05-30 西藏海思科制药有限公司 一种gspt1降解剂及其在医药上的应用
WO2024222918A1 (zh) * 2023-04-28 2024-10-31 中国药科大学 一种苯并六元杂环类gspt1蛋白降解剂及其应用
WO2025011624A1 (en) * 2023-07-11 2025-01-16 Etern Biopharma (Shanghai) Co., Ltd. Bifunctional compounds for androgen receptor degradation and methods of use
CN121532386A (zh) * 2023-07-28 2026-02-13 杭州中美华东制药有限公司 具有蛋白降解作用的芳胺类化合物
WO2025097092A1 (en) * 2023-11-02 2025-05-08 Neomorph, Inc. Substituted 3-(5-(4-hydroxypiperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and 3-(2-(4-hydroxypiperidin-4-yl)-5-oxo-5,7-dihydro-6h-pyrrolo[3,4-b]pyridin-6-yl)piperidine-2,6-dione derivatives and uses thereof
WO2025245178A1 (en) * 2024-05-21 2025-11-27 Innovo Therapeutics, Inc. Pak4, cstf2, or cstf2t protein degraders, pharmaceutical compositions, and therapeutic applications

Family Cites Families (12)

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Publication number Priority date Publication date Assignee Title
AU2012268036B2 (en) * 2011-06-06 2017-04-06 THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF STATE OF THE DEPARTMENT OF VETERANS AFFAIRS Methods of inhibiting muscle atrophy
TWI793151B (zh) * 2017-08-23 2023-02-21 瑞士商諾華公司 3-(1-氧異吲哚啉-2-基)之氫吡啶-2,6-二酮衍生物及其用途
JP7585034B2 (ja) * 2017-10-18 2024-11-18 ノバルティス アーゲー 選択的タンパク質分解のための組成物及び方法
EP3924055B1 (en) * 2019-02-15 2024-04-03 Novartis AG Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
CN113490528B (zh) * 2019-02-15 2024-12-03 诺华股份有限公司 3-(1-氧代-5-(哌啶-4-基)异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途
WO2020168172A1 (en) * 2019-02-15 2020-08-20 Zamboni Chem Solutions Inc. Conjugate compounds for the degradation of raf
CR20220234A (es) * 2019-10-30 2022-07-19 Dana Farber Cancer Inst Inc Degradadores de moléculas pequeñas de helios y procedimientos de uso
KR20220147109A (ko) * 2020-02-27 2022-11-02 노파르티스 아게 키메라 항원 수용체 발현 세포의 제조 방법
CN115916199A (zh) * 2020-06-23 2023-04-04 诺华股份有限公司 包含3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物的给药方案
IL301690A (en) * 2020-10-16 2023-05-01 Dana Farber Cancer Inst Inc Piperidinyl small molecule degraders of helios and methods of use
CN117355299A (zh) * 2021-04-29 2024-01-05 尼奥莫夫公司 取代的2-(2,6-二氧代哌啶-3-基)-5-(1-哌啶-4-基)异吲哚啉-1,3-二酮衍生物及其用途
CA3209633A1 (en) * 2021-04-29 2022-11-03 Tinghu Zhang Phthalimido cereblon complex binders and transcription factor degraders and methods of use

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DOP2022000091A (es) 2022-08-31
MX2022005232A (es) 2022-06-08
CR20220234A (es) 2022-07-19
EP4051386A4 (en) 2024-05-22
CN114650868A (zh) 2022-06-21
JP2023500611A (ja) 2023-01-10
PH12022550980A1 (en) 2023-10-09
IL292173A (en) 2022-06-01
WO2021087093A1 (en) 2021-05-06
CL2022001111A1 (es) 2022-11-18
JP7720833B2 (ja) 2025-08-08
PE20221457A1 (es) 2022-09-21
EP4051386A1 (en) 2022-09-07
AU2020374957A1 (en) 2022-04-28
US20230002397A1 (en) 2023-01-05
BR112022007867A2 (pt) 2022-07-12
KR20220092920A (ko) 2022-07-04

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