CN111201225A - 作为mek抑制剂的类香豆素环类化合物及其应用 - Google Patents

作为mek抑制剂的类香豆素环类化合物及其应用 Download PDF

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Publication number
CN111201225A
CN111201225A CN201880041369.3A CN201880041369A CN111201225A CN 111201225 A CN111201225 A CN 111201225A CN 201880041369 A CN201880041369 A CN 201880041369A CN 111201225 A CN111201225 A CN 111201225A
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compound
reaction
pharmaceutically acceptable
crude product
added
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CN111201225B (zh
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毛庆华
吴成德
黄勇
龚珍
黎健
陈曙辉
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CStone Pharmaceuticals Shanghai Co Ltd
CStone Pharmaceuticals Suzhou Co Ltd
KEYSTONE
CStone Pharmaceuticals
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CStone Pharmaceuticals Shanghai Co Ltd
CStone Pharmaceuticals Suzhou Co Ltd
KEYSTONE
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    • 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
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A61K31/37—Coumarins, e.g. psoralen
    • 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
    • A61K31/4353—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
    • A61K31/436—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 six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

一类作为MEK抑制剂的类香豆素环类化合物和包含此类化合物的药物组合物，以及它们在制备治疗MEK相关疾病的药物的应用。具体公开了式(Ⅰ)所示化合物及其药学上可接受的盐或其互变异构体。

Description

PCT国内申请，说明书已公开。

Claims (25)

  1. PCT国内申请，权利要求书已公开。
CN201880041369.3A 2017-06-23 2018-06-22 作为mek抑制剂的类香豆素环类化合物及其应用 Active CN111201225B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
CN201710488401 2017-06-23
CN201710488401X 2017-06-23
CN2018105965875 2018-06-11
CN201810596587 2018-06-11
PCT/CN2018/092457 WO2018233696A1 (zh) 2017-06-23 2018-06-22 作为mek抑制剂的类香豆素环类化合物及其应用

Publications (2)

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CN111201225A true CN111201225A (zh) 2020-05-26
CN111201225B CN111201225B (zh) 2021-11-05

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US (1) US11021486B2 (zh)
EP (1) EP3643308B1 (zh)
JP (1) JP6774578B2 (zh)
KR (1) KR102580179B1 (zh)
CN (1) CN111201225B (zh)
AU (1) AU2018289864B2 (zh)
BR (1) BR112019027292A2 (zh)
CA (1) CA3067941C (zh)
ES (1) ES2876293T3 (zh)
IL (1) IL271550B (zh)
MX (1) MX2019015431A (zh)
RU (1) RU2742234C1 (zh)
SA (1) SA519410865B1 (zh)
SG (1) SG11201912997TA (zh)
TW (1) TWI801394B (zh)
WO (1) WO2018233696A1 (zh)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112912380B (zh) * 2018-12-21 2023-08-11 基石药业（苏州）有限公司 一种mek抑制剂的晶型、无定形及其应用
LV15600A (lv) * 2020-05-18 2021-11-20 Latvijas Organiskās Sintēzes Institūts Kurkumīna dihidropiridonu atvasinājumi ar pretvēža aktivitāti
KR20230172548A (ko) * 2021-04-16 2023-12-22 이케나 온콜로지, 인코포레이티드 Mek 억제제 및 이의 용도
CN116036080B (zh) * 2023-04-03 2023-06-06 江西省林业科学院 吡喃并吡啶酮类化合物在制备治疗肝癌药物中的应用

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WO2008127274A2 (en) * 2006-09-22 2008-10-23 Ptc Therapeutics, Inc. Heterocyclic inhibitors of bacterial peptidyl trna hydrolase and uses thereof
CN102964326A (zh) * 2012-11-06 2013-03-13 北京大学 具有mek抑制功能的化合物及其制备方法与应用
CN105153142A (zh) * 2014-06-03 2015-12-16 复旦大学 香豆素母核的呋咱衍生物及抗肿瘤活性
CN105287509A (zh) * 2014-08-01 2016-02-03 陶建臣 一种mek激酶抑制剂
JP2016155776A (ja) * 2015-02-24 2016-09-01 学校法人兵庫医科大学 抗腫瘍効果増強剤および抗腫瘍剤

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AU763669B2 (en) * 1998-09-29 2003-07-31 Wyeth Holdings Corporation Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors
AR059339A1 (es) 2006-02-09 2008-03-26 Chugai Pharmaceutical Co Ltd Derivados de la cumarina para trastornos proliferativos de celulas, composicion farmaceutica y agente terapeutico que los contiene
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CN102137843A (zh) 2008-07-01 2011-07-27 健泰科生物技术公司 作为mek激酶抑制剂的异吲哚酮衍生物及其使用方法
US20140228418A1 (en) 2011-05-23 2014-08-14 Synta Pharmaceuticals Corp. Combination therapy of hsp90 inhibitory compounds with mek inhibitors
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WO2008127274A2 (en) * 2006-09-22 2008-10-23 Ptc Therapeutics, Inc. Heterocyclic inhibitors of bacterial peptidyl trna hydrolase and uses thereof
CN102964326A (zh) * 2012-11-06 2013-03-13 北京大学 具有mek抑制功能的化合物及其制备方法与应用
CN105153142A (zh) * 2014-06-03 2015-12-16 复旦大学 香豆素母核的呋咱衍生物及抗肿瘤活性
CN105287509A (zh) * 2014-08-01 2016-02-03 陶建臣 一种mek激酶抑制剂
JP2016155776A (ja) * 2015-02-24 2016-09-01 学校法人兵庫医科大学 抗腫瘍効果増強剤および抗腫瘍剤

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Also Published As

Publication number Publication date
IL271550B (en) 2021-03-25
CN111201225B (zh) 2021-11-05
MX2019015431A (es) 2021-03-30
KR20200015787A (ko) 2020-02-12
KR102580179B1 (ko) 2023-09-18
AU2018289864B2 (en) 2022-03-31
TW201904973A (zh) 2019-02-01
IL271550A (en) 2020-02-27
WO2018233696A1 (zh) 2018-12-27
BR112019027292A2 (pt) 2020-07-21
AU2018289864A1 (en) 2020-02-06
CA3067941C (en) 2020-08-18
US11021486B2 (en) 2021-06-01
US20200148695A1 (en) 2020-05-14
SG11201912997TA (en) 2020-01-30
EP3643308A4 (en) 2020-04-29
TWI801394B (zh) 2023-05-11
EP3643308A1 (en) 2020-04-29
SA519410865B1 (ar) 2022-07-25
CA3067941A1 (en) 2018-12-27
ES2876293T3 (es) 2021-11-12
EP3643308B1 (en) 2021-05-19
JP6774578B2 (ja) 2020-10-28
RU2742234C1 (ru) 2021-02-03
JP2020524705A (ja) 2020-08-20

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