CN103204825B - 作为蛋白激酶抑制剂的苯并噻唑化合物及其制备方法和用途 - Google Patents

作为蛋白激酶抑制剂的苯并噻唑化合物及其制备方法和用途 Download PDF

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Publication number
CN103204825B
CN103204825B CN201210190520.4A CN201210190520A CN103204825B CN 103204825 B CN103204825 B CN 103204825B CN 201210190520 A CN201210190520 A CN 201210190520A CN 103204825 B CN103204825 B CN 103204825B
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China
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formula
alkyl
hydrogen
compound
cycloalkyl
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CN201210190520.4A
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Chinese (zh)
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CN103204825A (zh
Inventor
田红旗
季聪慧
黄功超
孔丽
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Shanghai Kechow Pharma Inc
Original Assignee
KECHOW PHARMA Inc
TIANJIN BINJIANG PHARMACEUTICAL Inc
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Priority to CN201210190520.4A priority Critical patent/CN103204825B/zh
Application filed by KECHOW PHARMA Inc, TIANJIN BINJIANG PHARMACEUTICAL Inc filed Critical KECHOW PHARMA Inc
Priority to EP13738359.2A priority patent/EP2804855B1/en
Priority to CA2897259A priority patent/CA2897259C/en
Priority to PCT/CN2013/000037 priority patent/WO2013107283A1/en
Priority to NZ627631A priority patent/NZ627631A/en
Priority to JP2014551508A priority patent/JP6077006B2/ja
Priority to HK15103824.9A priority patent/HK1203486B/en
Priority to US14/372,731 priority patent/US9290468B2/en
Priority to AU2013201455A priority patent/AU2013201455B8/en
Publication of CN103204825A publication Critical patent/CN103204825A/zh
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Publication of CN103204825B publication Critical patent/CN103204825B/zh
Priority to US15/050,045 priority patent/US9937158B2/en
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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
    • A61K31/433—Thidiazoles
    • 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
    • A61K31/42—Oxazoles
    • A61K31/423—Oxazoles condensed with carbocyclic 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
    • A61K31/41—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
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
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    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/14—Thiadiazoles; Hydrogenated thiadiazoles condensed with carbocyclic rings or ring systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Emergency Medicine (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Ophthalmology & Optometry (AREA)
  • Vascular Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
CN201210190520.4A 2012-01-17 2012-06-08 作为蛋白激酶抑制剂的苯并噻唑化合物及其制备方法和用途 Active CN103204825B (zh)

Priority Applications (10)

Application Number Priority Date Filing Date Title
CN201210190520.4A CN103204825B (zh) 2012-01-17 2012-06-08 作为蛋白激酶抑制剂的苯并噻唑化合物及其制备方法和用途
AU2013201455A AU2013201455B8 (en) 2012-01-17 2013-01-16 Benzoheterocyclic compounds and use thereof
PCT/CN2013/000037 WO2013107283A1 (en) 2012-01-17 2013-01-16 Benzoheterocyclic compounds and use thereof
NZ627631A NZ627631A (en) 2012-01-17 2013-01-16 Benzoheterocyclic compounds and use thereof
JP2014551508A JP6077006B2 (ja) 2012-01-17 2013-01-16 ベンゾ複素環式化合物およびその使用
HK15103824.9A HK1203486B (en) 2012-01-17 2013-01-16 Benzoheterocyclic compounds and use thereof
EP13738359.2A EP2804855B1 (en) 2012-01-17 2013-01-16 Benzoheterocyclic compounds and use thereof
CA2897259A CA2897259C (en) 2012-01-17 2013-01-16 Benzoheterocyclic compounds and use thereof
US14/372,731 US9290468B2 (en) 2012-01-17 2013-01-16 Benzoheterocyclic compounds and use thereof
US15/050,045 US9937158B2 (en) 2012-01-17 2016-02-22 Benzoheterocyclic compounds and use thereof

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN201210014021.X 2012-01-17
CN201210014021 2012-01-17
CN201210014021X 2012-01-17
CN201210190520.4A CN103204825B (zh) 2012-01-17 2012-06-08 作为蛋白激酶抑制剂的苯并噻唑化合物及其制备方法和用途

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CN103204825A CN103204825A (zh) 2013-07-17
CN103204825B true CN103204825B (zh) 2015-03-04

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CN201210189087.2A Active CN103204827B (zh) 2012-01-17 2012-06-08 作为蛋白激酶抑制剂的苯并噻二唑化合物及其制备方法和用途
CN201210189086.8A Active CN103204822B (zh) 2012-01-17 2012-06-08 作为蛋白激酶抑制剂的苯并噁唑化合物及其制备方法和用途

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CN201210189086.8A Active CN103204822B (zh) 2012-01-17 2012-06-08 作为蛋白激酶抑制剂的苯并噁唑化合物及其制备方法和用途

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US (2) US9290468B2 (cg-RX-API-DMAC10.html)
EP (1) EP2804855B1 (cg-RX-API-DMAC10.html)
JP (1) JP6077006B2 (cg-RX-API-DMAC10.html)
CN (3) CN103204825B (cg-RX-API-DMAC10.html)
CA (1) CA2897259C (cg-RX-API-DMAC10.html)
NZ (1) NZ627631A (cg-RX-API-DMAC10.html)
WO (1) WO2013107283A1 (cg-RX-API-DMAC10.html)

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CN104710417B (zh) * 2013-12-11 2020-09-08 上海科州药物研发有限公司 氮杂吲哚类衍生物及其合成方法
CN105384738B (zh) * 2014-08-21 2017-08-29 上海科州药物研发有限公司 作为蛋白激酶抑制剂的杂环类化合物及其制备方法和用途
CN105859543A (zh) * 2016-05-06 2016-08-17 蚌埠中实化学技术有限公司 一种2,6-二氟-4-溴苯甲酰氯的制备方法
CN111205244B (zh) * 2018-11-22 2023-08-18 上海科技大学 噻唑并环类化合物、其制备方法、中间体和应用
CA3129665A1 (en) 2019-03-21 2020-09-24 Onxeo A dbait molecule in combination with kinase inhibitor for the treatment of cancer
KR20220098759A (ko) 2019-11-08 2022-07-12 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) 키나제 억제제에 대해 내성을 획득한 암의 치료 방법
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
CN113440616A (zh) * 2020-03-25 2021-09-28 上海科州药物研发有限公司 Ras或raf突变型癌症的联合疗法
PE20260035A1 (es) * 2023-02-10 2026-01-09 Shanghai Kechow Pharma Inc Polimorfo como inhibidor de la proteina quinasa mek, metodo de preparacion y uso del mismo
EP4788839A1 (en) 2023-10-03 2026-08-12 Institut National de la Santé et de la Recherche Médicale Methods of prognosis and treatment of patients suffering from melanoma
WO2025242163A1 (zh) * 2024-05-23 2025-11-27 上海科州药物股份有限公司 蛋白激酶mek抑制剂的盐及其用途
WO2025261499A1 (zh) * 2024-06-20 2025-12-26 上海科州药物股份有限公司 蛋白激酶Mek抑制剂苯并噻唑的颗粒药物组合物
CN120463660A (zh) * 2024-09-30 2025-08-12 上海科州药物股份有限公司 大规模制备妥拉美替尼及其中间体的方法

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