CN109689645B - 作为nik抑制剂的氰基吲哚啉衍生物 - Google Patents

作为nik抑制剂的氰基吲哚啉衍生物 Download PDF

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CN109689645B
CN109689645B CN201780053613.3A CN201780053613A CN109689645B CN 109689645 B CN109689645 B CN 109689645B CN 201780053613 A CN201780053613 A CN 201780053613A CN 109689645 B CN109689645 B CN 109689645B
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CN109689645A (zh
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I·斯坦斯菲尔德
O·A·G·奎伊罗勒
Y·A·E·里格奈
格哈德·马克斯·格罗斯
埃德加·雅各比
L·米尔波尔
西蒙·理查德·格林
G·海恩德
J·J·库拉戈维斯基
C·马克勒奥德
S·E·马恩
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Janssen Pharmaceutica NV
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    • 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
    • C07D498/04—Ortho-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
    • A61K31/495—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
    • A61K31/5365—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 ortho- or peri-condensed with heterocyclic ring 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
    • A61K31/535—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
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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
    • C07D403/02—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 two hetero rings
    • C07D403/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • 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
    • C07D405/02—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 two hetero rings
    • C07D405/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • 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
    • C07D487/04—Ortho-condensed 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
    • 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
    • C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN201780053613.3A 2016-06-30 2017-06-29 作为nik抑制剂的氰基吲哚啉衍生物 Active CN109689645B (zh)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
EP16177147 2016-06-30
EP16177131 2016-06-30
EP16177142.3 2016-06-30
EP16177142 2016-06-30
EP16177147.2 2016-06-30
EP16177131.6 2016-06-30
PCT/EP2017/066125 WO2018002219A1 (en) 2016-06-30 2017-06-29 Cyanoindoline derivatives as nik inhibitors

Publications (2)

Publication Number Publication Date
CN109689645A CN109689645A (zh) 2019-04-26
CN109689645B true CN109689645B (zh) 2022-06-03

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US (2) US20190119299A1 (enExample)
EP (1) EP3478673B1 (enExample)
JP (1) JP6936814B2 (enExample)
KR (1) KR102587619B1 (enExample)
CN (1) CN109689645B (enExample)
AU (1) AU2017289317B2 (enExample)
ES (1) ES2837157T3 (enExample)
WO (1) WO2018002219A1 (enExample)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI739783B (zh) 2016-01-22 2021-09-21 比利時商健生藥品公司 作為nik抑制劑的新穎的經取代氰基吲哚啉衍生物
US11001569B2 (en) 2016-01-22 2021-05-11 Janssen Pharmaceutica Nv 6-membered heteroaromatic substituted cyanoindoline derivatives as NIK inhibitors
CN109641882B (zh) 2016-06-30 2022-10-28 杨森制药有限公司 作为nik抑制剂的杂芳族衍生物
KR102587619B1 (ko) 2016-06-30 2023-10-11 잔센파마슈티카엔.브이. Nik 억제제로서의 시아노인돌린 유도체
MA56038B1 (fr) 2019-05-31 2024-11-29 Janssen Pharmaceutica Nv Inhibiteurs à petite molécule de kinase induisant nf-kb
JP7633989B2 (ja) * 2019-07-04 2025-02-20 レゴー・ファーマシューティカルズ，インコーポレーテッド Ｈｐｋ１阻害剤およびその使用
TW202304906A (zh) * 2021-04-08 2023-02-01 大陸商杭州阿諾生物醫藥科技有限公司 高活性hpk1激酶抑制劑
CN114380806B (zh) * 2022-03-24 2022-06-10 中国药科大学 2-氨基-4-吲哚基嘧啶类化合物及其制备方法与应用

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WO2003030909A1 (en) * 2001-09-25 2003-04-17 Bayer Pharmaceuticals Corporation 2- and 4-aminopyrimidines n-substtituded by a bicyclic ring for use as kinase inhibitors in the treatment of cancer
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WO2009158011A1 (en) * 2008-06-26 2009-12-30 Amgen Inc. Alkynyl alcohols as kinase inhibitors
WO2010042337A1 (en) * 2008-10-07 2010-04-15 Merck Sharp & Dohme Corp. Novel 6-azaindole aminopyrimidine derivatives having nik inhibitory activity
CN105143223A (zh) * 2013-04-24 2015-12-09 詹森药业有限公司 3-(2-氨基嘧啶-4-基)-5-(3-羟丙炔基)-1h-吡咯并[2,3-c]吡啶衍生物作为nik抑制剂用于治疗癌症
CN105579452A (zh) * 2013-09-26 2016-05-11 詹森药业有限公司 作为NIK抑制剂的新型3-(1H-吡唑-4-基)-1H-吡咯并[2,3-c]吡啶衍生物
CN105579451A (zh) * 2013-09-26 2016-05-11 詹森药业有限公司 作为NIK抑制剂的新型1-(4-嘧啶基)-1H-吡咯并[3,2-c]吡啶衍生物

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* Cited by examiner, † Cited by third party
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WO2002079197A1 (en) * 2001-03-29 2002-10-10 Vertex Pharmaceuticals Incorporated Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases
WO2003030909A1 (en) * 2001-09-25 2003-04-17 Bayer Pharmaceuticals Corporation 2- and 4-aminopyrimidines n-substtituded by a bicyclic ring for use as kinase inhibitors in the treatment of cancer
CN101039919A (zh) * 2004-10-13 2007-09-19 惠氏公司 经n－苯磺酰基取代的苯胺基嘧啶类似物
WO2009158011A1 (en) * 2008-06-26 2009-12-30 Amgen Inc. Alkynyl alcohols as kinase inhibitors
WO2010042337A1 (en) * 2008-10-07 2010-04-15 Merck Sharp & Dohme Corp. Novel 6-azaindole aminopyrimidine derivatives having nik inhibitory activity
CN105143223A (zh) * 2013-04-24 2015-12-09 詹森药业有限公司 3-(2-氨基嘧啶-4-基)-5-(3-羟丙炔基)-1h-吡咯并[2,3-c]吡啶衍生物作为nik抑制剂用于治疗癌症
CN105579452A (zh) * 2013-09-26 2016-05-11 詹森药业有限公司 作为NIK抑制剂的新型3-(1H-吡唑-4-基)-1H-吡咯并[2,3-c]吡啶衍生物
CN105579451A (zh) * 2013-09-26 2016-05-11 詹森药业有限公司 作为NIK抑制剂的新型1-(4-嘧啶基)-1H-吡咯并[3,2-c]吡啶衍生物

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AU2017289317B2 (en) 2021-04-01
CN109689645A (zh) 2019-04-26
AU2017289317A1 (en) 2019-01-17
US11186589B2 (en) 2021-11-30
JP6936814B2 (ja) 2021-09-22
US20210032267A1 (en) 2021-02-04
US20190119299A1 (en) 2019-04-25
ES2837157T3 (es) 2021-06-29
WO2018002219A1 (en) 2018-01-04
CA3027418A1 (en) 2018-01-04
EP3478673A1 (en) 2019-05-08
JP2019524646A (ja) 2019-09-05
KR20190025949A (ko) 2019-03-12
EP3478673B1 (en) 2020-09-16
KR102587619B1 (ko) 2023-10-11

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