CN111868058A - 一种fgfr抑制剂、其制备方法和在药学上的应用 - Google Patents

一种fgfr抑制剂、其制备方法和在药学上的应用 Download PDF

Info

Publication number
CN111868058A
CN111868058A CN201980019954.8A CN201980019954A CN111868058A CN 111868058 A CN111868058 A CN 111868058A CN 201980019954 A CN201980019954 A CN 201980019954A CN 111868058 A CN111868058 A CN 111868058A
Authority
CN
China
Prior art keywords
deuterium
radical
substituted
cycloalkyl
alkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201980019954.8A
Other languages
English (en)
Other versions
CN111868058B (zh
Inventor
邓海兵
应海燕
喻红平
陈椎
徐耀昌
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abbisko Therapeutics Co Ltd
Original Assignee
Abbisko Therapeutics Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Abbisko Therapeutics Co Ltd filed Critical Abbisko Therapeutics Co Ltd
Publication of CN111868058A publication Critical patent/CN111868058A/zh
Application granted granted Critical
Publication of CN111868058B publication Critical patent/CN111868058B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K31/4353—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
    • A61K31/4375—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 nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • 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
    • A61K31/4985—Pyrazines or piperazines 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
    • A61K31/495—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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

提供一种具有式(I)结构的FGFR抑制剂、其制备方法和在药学上的应用，各取代基的定义如说明书和权利要求书所述。所述系列化合物可广泛应用于制备***、癌症、骨髓增生性疾病、骨骼或软骨细胞紊乱、低磷血症的药物，有望开发成新一代FGFR抑制剂药物。

Description

PCT国内申请，说明书已公开。

Claims (17)

  1. PCT国内申请，权利要求书已公开。
CN201980019954.8A 2018-05-25 2019-05-23 一种fgfr抑制剂、其制备方法和在药学上的应用 Active CN111868058B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201810516734 2018-05-25
CN2018105167343 2018-05-25
PCT/CN2019/088158 WO2019223766A1 (zh) 2018-05-25 2019-05-23 一种fgfr抑制剂、其制备方法和在药学上的应用

Publications (2)

Publication Number Publication Date
CN111868058A true CN111868058A (zh) 2020-10-30
CN111868058B CN111868058B (zh) 2023-06-13

Family

ID=68615694

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201980019954.8A Active CN111868058B (zh) 2018-05-25 2019-05-23 一种fgfr抑制剂、其制备方法和在药学上的应用

Country Status (2)

Country Link
CN (1) CN111868058B (zh)
WO (1) WO2019223766A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116171155A (zh) * 2020-12-08 2023-05-26 上海和誉生物医药科技有限公司 吡啶并[2,3-d]嘧啶-2(1H)-酮衍生物及其制备方法和应用

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102396930B1 (ko) * 2020-01-15 2022-05-12 한국과학기술연구원 피리도[3,4-d]피리미딘 유도체 및 이를 포함하는 치료용 약학 조성물
WO2022037592A1 (zh) * 2020-08-17 2022-02-24 南京明德新药研发有限公司 嘧啶并环类化合物

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1157619A (zh) * 1994-09-07 1997-08-20 卡尔·托马博士公司 嘧啶并[5，4-d]嘧啶，含该化合物的药物，其用途及其制备方法
CN103261167A (zh) * 2010-12-17 2013-08-21 霍夫曼-拉罗奇有限公司 取代的6，6-稠合含氮杂环化合物及其用途
CN109661394A (zh) * 2016-12-19 2019-04-19 上海和誉生物医药科技有限公司 Fgfr4抑制剂、其制备方法与药学上的应用
CN109745325A (zh) * 2017-11-08 2019-05-14 上海翰森生物医药科技有限公司 Fgfr4抑制剂、其制备方法和用途

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RS62233B1 (sr) * 2012-07-11 2021-09-30 Blueprint Medicines Corp Inhibitori receptora fibroblast faktora rasta
CN105307657B (zh) * 2013-03-15 2020-07-10 西建卡尔有限责任公司 杂芳基化合物和其用途
CN110028491B (zh) * 2013-10-25 2022-02-11 缆图药品公司 纤维母细胞生长因子受体抑制剂

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1157619A (zh) * 1994-09-07 1997-08-20 卡尔·托马博士公司 嘧啶并[5，4-d]嘧啶，含该化合物的药物，其用途及其制备方法
CN103261167A (zh) * 2010-12-17 2013-08-21 霍夫曼-拉罗奇有限公司 取代的6，6-稠合含氮杂环化合物及其用途
CN109661394A (zh) * 2016-12-19 2019-04-19 上海和誉生物医药科技有限公司 Fgfr4抑制剂、其制备方法与药学上的应用
CN109745325A (zh) * 2017-11-08 2019-05-14 上海翰森生物医药科技有限公司 Fgfr4抑制剂、其制备方法和用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PAOLO INNOCENTI等: "Expanding the scope of fused pyrimidines as kinase inhibitor scaffolds: synthesis and modification of pyrido[3,4- d]pyrimidines", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116171155A (zh) * 2020-12-08 2023-05-26 上海和誉生物医药科技有限公司 吡啶并[2,3-d]嘧啶-2(1H)-酮衍生物及其制备方法和应用

Also Published As

Publication number Publication date
CN111868058B (zh) 2023-06-13
WO2019223766A1 (zh) 2019-11-28

Similar Documents

Publication Publication Date Title
TWI725266B (zh) Fgfr4抑制劑、其製備方法與藥學上的應用
CN110461841B (zh) 一种具有csf1r抑制活性的氮杂芳基衍生物、其制备方法和应用
CA3032921A1 (en) Heterocyclic compounds as fgfr inhibitors
CN111868058B (zh) 一种fgfr抑制剂、其制备方法和在药学上的应用
CN110546145A (zh) 一种氮杂芳基衍生物、其制备方法和在药学上的应用
JP2023145548A (ja) Ｃｄ７３阻害剤、その製造方法と応用
CN110691775B (zh) 一种具有fgfr4抑制活性的醛基吡啶衍生物、其制备方法和应用
CN110461849B (zh) 一种csf1r抑制剂及其制备方法和应用
WO2021027503A1 (zh) 三环类化合物、其制备方法、中间体及应用
CN111936493B (zh) 一种高选择性FGFRi抑制剂及其制备方法和应用
CN112119064B (zh) Fgfr抑制剂、其制备方法和应用
CN111763217B (zh) 一类噻吩并氮杂环类化合物、制备方法和用途
CN114369097B (zh) 杂芳环类AhR抑制剂
CN116003406A (zh) 杂芳环氮氧化合物及其制备方法和应用

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant