CN115298175B - 可用作免疫抑制剂的大环pad4抑制剂 - Google Patents

可用作免疫抑制剂的大环pad4抑制剂 Download PDF

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Publication number
CN115298175B
CN115298175B CN202180022507.5A CN202180022507A CN115298175B CN 115298175 B CN115298175 B CN 115298175B CN 202180022507 A CN202180022507 A CN 202180022507A CN 115298175 B CN115298175 B CN 115298175B
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substituted
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alkylene
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pharmaceutically acceptable
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CN115298175A (zh
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K·恩古
C·阿南齐亚托
J·V·杜西亚
D·S·加德纳
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Bristol Myers Squibb Co
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    • 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
    • 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
    • C07D471/22—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 systems contains four or more hetero rings
    • 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
    • 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
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • C07D487/04—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
    • C07D487/22—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 four or more hetero rings
    • 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
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN202180022507.5A 2020-02-06 2021-02-05 可用作免疫抑制剂的大环pad4抑制剂 Active CN115298175B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202062970832P 2020-02-06 2020-02-06
US62/970,832 2020-02-06
PCT/US2021/016698 WO2021158840A1 (en) 2020-02-06 2021-02-05 Macrocyclic pad4 inhibitors useful as immunosuppressant

Publications (2)

Publication Number Publication Date
CN115298175A CN115298175A (zh) 2022-11-04
CN115298175B true CN115298175B (zh) 2024-05-07

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US (1) US12492202B2 (https=)
EP (1) EP4100405A1 (https=)
JP (1) JP7711073B2 (https=)
KR (1) KR20220137694A (https=)
CN (1) CN115298175B (https=)
WO (1) WO2021158840A1 (https=)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021158840A1 (en) 2020-02-06 2021-08-12 Bristol-Myers Squibb Company Macrocyclic pad4 inhibitors useful as immunosuppressant
TW202140477A (zh) 2020-02-12 2021-11-01 美商必治妥美雅史谷比公司 雜環ｐａｄ４抑制劑
WO2021222353A1 (en) 2020-04-30 2021-11-04 Gilead Sciences, Inc. Macrocyclic inhibitors of peptidylarginine deiminases
TW202233174A (zh) 2020-12-22 2022-09-01 美商基利科學股份有限公司 肽基精胺酸去亞胺酶之抑制劑
WO2022140390A1 (en) 2020-12-22 2022-06-30 Gilead Sciences, Inc. Inhibitors of peptidylarginine deiminases
KR20260041867A (ko) 2023-07-21 2026-03-27 브리스톨-마이어스 스큅 컴퍼니 Pad4 조정제의 시트룰린화 및 활성을 평가하는 방법
WO2026020127A2 (en) 2024-07-19 2026-01-22 Bristol-Myers Squibb Company Methods of assessing citrullination and activity of pad2 modulators

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104470919A (zh) * 2012-07-26 2015-03-25 葛兰素集团有限公司 作为pad4抑制剂的2-(氮杂吲哚-2-基)苯并咪唑
CN108601770A (zh) * 2015-12-09 2018-09-28 帕德罗科治疗公司 Pad4的氮杂-苯并咪唑抑制剂
CN109069869A (zh) * 2015-12-09 2018-12-21 帕德罗科治疗公司 双环pad4抑制剂
CN109790162A (zh) * 2016-07-27 2019-05-21 帕德罗科治疗公司 Pad4的共价抑制剂

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20180005250A (ko) * 2015-05-21 2018-01-15 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 Pad4 억제제로서의 벤조이미다졸 유도체
CA3015482A1 (en) 2016-02-23 2017-08-31 Padlock Therapeutics, Inc. Heteroaryl inhibitors of pad4
US11026937B2 (en) 2016-09-12 2021-06-08 Padlock Therapeutics, Inc. Heteroaryl inhibitors of PAD4
MX2021001471A (es) 2018-08-08 2021-04-28 Bristol Myers Squibb Co Benzimidazoles sustituidos como inhibidores de peptidil arginina deiminasa 4 (pad4).
JP7447080B2 (ja) 2018-08-08 2024-03-11 ブリストル－マイヤーズ スクイブ カンパニー Ｐａｄ４阻害剤としての置換チエノピロール
MX2021001565A (es) 2018-08-08 2021-04-19 Bristol Myers Squibb Co Inhibidores tipo indol y azaindol de enzimas peptidil arginina deiminasas (pad).
US20220348562A1 (en) 2018-08-08 2022-11-03 Bristol-Myers Squibb Company Benzimidazole inhibitors of pad enzymes
WO2021158840A1 (en) 2020-02-06 2021-08-12 Bristol-Myers Squibb Company Macrocyclic pad4 inhibitors useful as immunosuppressant
TW202140477A (zh) 2020-02-12 2021-11-01 美商必治妥美雅史谷比公司 雜環ｐａｄ４抑制劑

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104470919A (zh) * 2012-07-26 2015-03-25 葛兰素集团有限公司 作为pad4抑制剂的2-(氮杂吲哚-2-基)苯并咪唑
CN108601770A (zh) * 2015-12-09 2018-09-28 帕德罗科治疗公司 Pad4的氮杂-苯并咪唑抑制剂
CN109069869A (zh) * 2015-12-09 2018-12-21 帕德罗科治疗公司 双环pad4抑制剂
CN109790162A (zh) * 2016-07-27 2019-05-21 帕德罗科治疗公司 Pad4的共价抑制剂

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WO2021158840A1 (en) 2021-08-12
JP7711073B2 (ja) 2025-07-22
US20230203039A1 (en) 2023-06-29
KR20220137694A (ko) 2022-10-12
EP4100405A1 (en) 2022-12-14
US12492202B2 (en) 2025-12-09
CN115298175A (zh) 2022-11-04
JP2023512557A (ja) 2023-03-27

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