CN112789087B - Pad酶的苯并咪唑抑制剂 - Google Patents

Pad酶的苯并咪唑抑制剂 Download PDF

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CN112789087B
CN112789087B CN201980064964.3A CN201980064964A CN112789087B CN 112789087 B CN112789087 B CN 112789087B CN 201980064964 A CN201980064964 A CN 201980064964A CN 112789087 B CN112789087 B CN 112789087B
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CN112789087A (zh
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K·恩古
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Bristol Myers Squibb Co
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    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4192—1,2,3-Triazoles
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
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    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
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    • A61K31/425—Thiazoles
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    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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    • 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
    • A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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    • 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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    • 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
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    • C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
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    • 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

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  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
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  • Oncology (AREA)
  • Immunology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN201980064964.3A 2018-08-08 2019-08-07 Pad酶的苯并咪唑抑制剂 Active CN112789087B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862715845P 2018-08-08 2018-08-08
US62/715,845 2018-08-08
PCT/US2019/045459 WO2020033514A1 (en) 2018-08-08 2019-08-07 Benzimidazole inhibitors of pad enzymes

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CN112789087A CN112789087A (zh) 2021-05-11
CN112789087B true CN112789087B (zh) 2024-08-13

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US (1) US20220348562A1 (https=)
EP (1) EP3833439B1 (https=)
JP (1) JP7434281B2 (https=)
KR (1) KR20210042933A (https=)
CN (1) CN112789087B (https=)
ES (1) ES2956090T3 (https=)
WO (1) WO2020033514A1 (https=)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3833671B1 (en) 2018-08-08 2022-08-24 Bristol-Myers Squibb Company Substituted thienopyrroles as pad4 inhibitors
AU2019319835A1 (en) 2018-08-08 2021-03-25 Bristol-Myers Squibb Company Indole and azaindole inhibitors of PAD enzymes
EP4100405A1 (en) 2020-02-06 2022-12-14 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
EP4143189A1 (en) * 2020-04-30 2023-03-08 Gilead Sciences, Inc. Macrocyclic inhibitors of peptidylarginine deiminases
TW202241884A (zh) 2020-12-22 2022-11-01 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
WO2022140428A2 (en) 2020-12-22 2022-06-30 Gilead Sciences, Inc. Inhibitors of peptidylarginine deiminases
WO2025024265A1 (en) 2023-07-21 2025-01-30 Bristol-Myers Squibb Company Methods of assessing citrullination and activity of pad4 modulators
WO2026020127A2 (en) 2024-07-19 2026-01-22 Bristol-Myers Squibb Company Methods of assessing citrullination and activity of pad2 modulators

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001021634A1 (en) * 1999-09-21 2001-03-29 Lion Bioscience Ag Benzimidazole derivatives and combinatorial libraries thereof
WO2010051245A1 (en) * 2008-11-03 2010-05-06 Merck Sharp & Dohme Corp. Benzimidazole and aza-benzimidazole carboxamides
WO2017100594A1 (en) * 2015-12-09 2017-06-15 Padlock Therapeutics, Inc. Bicyclic inhibitors of pad4
WO2017147102A1 (en) * 2016-02-23 2017-08-31 Padlock Therapeutics, Inc. Heteroaryl inhibitors of pad4
CN107849015A (zh) * 2015-05-21 2018-03-27 葛兰素知识产权发展有限公司 作为pad4抑制剂的苯并咪唑衍生物

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RS55684B1 (sr) * 2012-07-26 2017-07-31 Glaxo Group Ltd 2-(azaindol-2-il)benzimidazoli kao pad4 inhibitori
AR107030A1 (es) * 2015-12-09 2018-03-14 Padlock Therapeutics Inc Inhibidores aza-bencimidazol de pad4
KR102398941B1 (ko) * 2016-07-27 2022-05-17 패들락 테라퓨틱스, 인코포레이티드 Pad4의 공유결합성 억제제
CN107311933B (zh) 2017-06-28 2020-12-22 中国人民解放军军事医学科学院毒物药物研究所 一类苯并咪唑衍生物，及其制备方法和用途

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001021634A1 (en) * 1999-09-21 2001-03-29 Lion Bioscience Ag Benzimidazole derivatives and combinatorial libraries thereof
WO2010051245A1 (en) * 2008-11-03 2010-05-06 Merck Sharp & Dohme Corp. Benzimidazole and aza-benzimidazole carboxamides
CN107849015A (zh) * 2015-05-21 2018-03-27 葛兰素知识产权发展有限公司 作为pad4抑制剂的苯并咪唑衍生物
WO2017100594A1 (en) * 2015-12-09 2017-06-15 Padlock Therapeutics, Inc. Bicyclic inhibitors of pad4
WO2017147102A1 (en) * 2016-02-23 2017-08-31 Padlock Therapeutics, Inc. Heteroaryl inhibitors of pad4

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KR20210042933A (ko) 2021-04-20
EP3833439B1 (en) 2023-07-12
ES2956090T3 (es) 2023-12-13
CN112789087A (zh) 2021-05-11
JP7434281B2 (ja) 2024-02-20
JP2021534104A (ja) 2021-12-09
WO2020033514A1 (en) 2020-02-13
US20220348562A1 (en) 2022-11-03
EP3833439A1 (en) 2021-06-16

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