CN109983016A - 嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途 - Google Patents

嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途 Download PDF

Info

Publication number
CN109983016A
CN109983016A CN201780071569.9A CN201780071569A CN109983016A CN 109983016 A CN109983016 A CN 109983016A CN 201780071569 A CN201780071569 A CN 201780071569A CN 109983016 A CN109983016 A CN 109983016A
Authority
CN
China
Prior art keywords
compound
substituted
cancer
alkyl
aryl
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
CN201780071569.9A
Other languages
English (en)
Other versions
CN109983016B (zh
Inventor
张翱
丁健
谢华
宋子兰
薛宇
童林江
耿美玉
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.)
Shanghai Institute of Materia Medica of CAS
Original Assignee
Shanghai Institute of Materia Medica of CAS
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 Shanghai Institute of Materia Medica of CAS filed Critical Shanghai Institute of Materia Medica of CAS
Publication of CN109983016A publication Critical patent/CN109983016A/zh
Application granted granted Critical
Publication of CN109983016B publication Critical patent/CN109983016B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/14—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
    • A61K31/519—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
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • C07D487/12—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 three hetero rings
    • C07D487/14—Ortho-condensed systems

Abstract

本发明涉及一种嘧啶并[5,4‑b]吲嗪或嘧啶并[5,4‑b]吡呤化合物、其制备方法及用途。本发明的化合物在分子水平及细胞水平对于BTK的抑制活性均较好。重要的是，本发明的化合物对普通人B淋巴瘤细胞Ramos细胞活性较低，对BTK敏感的人弥漫大B淋巴瘤TMD8细胞具有高活性，这表明这种结构类型化合物的选择性较高，脱靶及相应的副作用较低，是一类具有开发潜力的BTK选择性抑制剂。

Description

PCT国内申请，说明书已公开。

Claims (10)

  1. PCT国内申请，权利要求书已公开。
CN201780071569.9A 2016-11-24 2017-11-24 嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途 Active CN109983016B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201611045301.1A CN108101905A (zh) 2016-11-24 2016-11-24 嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途
CN2016110453011 2016-11-24
PCT/CN2017/112729 WO2018095398A1 (zh) 2016-11-24 2017-11-24 嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途

Publications (2)

Publication Number Publication Date
CN109983016A true CN109983016A (zh) 2019-07-05
CN109983016B CN109983016B (zh) 2022-02-01

Family

ID=62194774

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201611045301.1A Pending CN108101905A (zh) 2016-11-24 2016-11-24 嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途
CN201780071569.9A Active CN109983016B (zh) 2016-11-24 2017-11-24 嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN201611045301.1A Pending CN108101905A (zh) 2016-11-24 2016-11-24 嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途

Country Status (9)

Country Link
US (1) US10829491B2 (zh)
EP (1) EP3546460B1 (zh)
JP (1) JP6804647B2 (zh)
KR (1) KR102359993B1 (zh)
CN (2) CN108101905A (zh)
AU (1) AU2017366529B2 (zh)
CA (1) CA3044889C (zh)
RU (1) RU2721774C1 (zh)
WO (1) WO2018095398A1 (zh)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3108065A1 (en) 2018-07-31 2020-02-06 Loxo Oncology, Inc. Spray-dried dispersions, formulations, and polymorphs of (s)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1h-pyrazole-4-carboxamide
AU2020242287A1 (en) 2019-03-21 2021-09-02 INSERM (Institut National de la Santé et de la Recherche Médicale) A Dbait molecule in combination with kinase inhibitor for the treatment of cancer
US20220204518A1 (en) * 2019-04-24 2022-06-30 Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences Pyrimido[5,4-b]pyrrolizin compound, optical isomer thereof, preparation method therefor and use thereof
WO2021037188A1 (zh) * 2019-08-29 2021-03-04 中国科学院上海药物研究所 嘧啶并[5,4-b]吡呤化合物的制药用途
WO2021057796A1 (zh) * 2019-09-29 2021-04-01 深圳市塔吉瑞生物医药有限公司 取代的稠合三环衍生物及其组合物及用途
WO2021089791A1 (en) 2019-11-08 2021-05-14 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the treatment of cancers that have acquired resistance to kinase inhibitors
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
CN114478548A (zh) * 2020-10-23 2022-05-13 上海润石医药科技有限公司 一种布鲁顿酪氨酸激酶抑制剂的用途
CN114478547A (zh) * 2020-10-23 2022-05-13 上海润石医药科技有限公司 固体形式的布鲁顿酪氨酸激酶抑制剂化合物及其用途
CN113024556B (zh) * 2021-04-01 2022-03-01 中国科学技术大学 一种含吲哚骨架的稠环化合物的制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104125959A (zh) * 2011-11-03 2014-10-29 霍夫曼-拉罗奇有限公司 作为btk活性的抑制剂的杂芳基吡啶酮和氮杂-吡啶酮化合物
CN104136438A (zh) * 2012-02-23 2014-11-05 大鹏药品工业株式会社 喹啉基吡咯并嘧啶基稠环化合物或其盐
CN105073752A (zh) * 2013-02-22 2015-11-18 大鹏药品工业株式会社 制备三环化合物的方法以及可通过所述制备方法制备的三环化合物
CN105358546A (zh) * 2013-06-25 2016-02-24 百时美施贵宝公司 用作激酶抑制剂的经取代的四氢咔唑及咔唑甲酰胺化合物

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2081039C1 (ru) * 1994-08-04 1997-06-10 Давид Моисеевич Ихельсон Конвейерная установка
CA2450777C (en) * 2001-08-10 2013-04-09 Novartis Ag Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia
KR101315610B1 (ko) * 2006-09-22 2013-10-10 파마시클릭스, 인코포레이티드 브루톤 티로신 키나제 억제제
CA2874756C (en) * 2007-03-28 2018-05-29 Pharmacyclics, Inc. Inhibitors of bruton's tyrosine kinase
ES2660418T3 (es) * 2008-07-16 2018-03-22 Pharmacyclics Llc Inhibidores de la tirosina quinasa de Bruton para el tratamiento de tumores sólidos
ES2950569T3 (es) * 2011-07-19 2023-10-11 Merck Sharp & Dohme (S)-4-(8-amino-3-(1-(but-2-inoil)pirrolidin-2-il)imidazo[1,5-a]pirazin-1-il)-2-metoxi-n-(piridin-2-il)benzamida como inhibidor de la Btk
US9266895B2 (en) * 2012-09-10 2016-02-23 Principia Biopharma Inc. Substituted pyrazolo[3,4-d]pyrimidines as kinase inhibitors
US9650386B2 (en) * 2013-08-22 2017-05-16 Taiho Pharmaceutical Co., Inc. Quinoline-substituted compound
WO2015057992A1 (en) * 2013-10-16 2015-04-23 Izumi Raquel Btk inhibitors for hematopoietic mobilization
WO2017064558A1 (ja) * 2015-10-14 2017-04-20 大鵬薬品工業株式会社 新規免疫賦活化剤
EP3371189A1 (en) * 2015-11-06 2018-09-12 Acerta Pharma B.V. Imidazopyrazine inhibitors of bruton's tyrosine kinase
JP2018002644A (ja) * 2016-06-30 2018-01-11 大鵬薬品工業株式会社 （Ｓ）−Ｎ−（４−アミノ−５−（キノリン−３−イル）−６，７，８，９−テトラヒドロピリミド［５，４−ｂ］インドリジン−８−イル）アクリルアミドの結晶
JP2018002662A (ja) * 2016-07-01 2018-01-11 大鵬薬品工業株式会社 キノリルピロロピリミジル縮合環化合物を合成するために有用な中間体
JOP20190073A1 (ar) * 2016-10-31 2019-04-07 Taiho Pharmaceutical Co Ltd مثبط انتقائي لمستقبل عامل نمو بشروي (egfr) لطافر إدخال exon 20

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104125959A (zh) * 2011-11-03 2014-10-29 霍夫曼-拉罗奇有限公司 作为btk活性的抑制剂的杂芳基吡啶酮和氮杂-吡啶酮化合物
CN104136438A (zh) * 2012-02-23 2014-11-05 大鹏药品工业株式会社 喹啉基吡咯并嘧啶基稠环化合物或其盐
CN105073752A (zh) * 2013-02-22 2015-11-18 大鹏药品工业株式会社 制备三环化合物的方法以及可通过所述制备方法制备的三环化合物
CN105358546A (zh) * 2013-06-25 2016-02-24 百时美施贵宝公司 用作激酶抑制剂的经取代的四氢咔唑及咔唑甲酰胺化合物

Also Published As

Publication number Publication date
RU2721774C1 (ru) 2020-05-22
AU2017366529A1 (en) 2019-07-11
JP6804647B2 (ja) 2020-12-23
CA3044889A1 (en) 2018-05-31
EP3546460A4 (en) 2019-12-18
CN108101905A (zh) 2018-06-01
EP3546460B1 (en) 2020-07-08
WO2018095398A1 (zh) 2018-05-31
EP3546460A1 (en) 2019-10-02
US10829491B2 (en) 2020-11-10
JP2020503266A (ja) 2020-01-30
CN109983016B (zh) 2022-02-01
AU2017366529B2 (en) 2021-08-19
CA3044889C (en) 2021-08-03
KR20190080951A (ko) 2019-07-08
KR102359993B1 (ko) 2022-02-07
US20190292183A1 (en) 2019-09-26

Similar Documents

Publication Publication Date Title
CN109983016A (zh) 嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途
US9890168B2 (en) 2,4-disubstituted 7H-pyrrolo[2,3-d]pyrimidine derivative, preparation method and medicinal use thereof
CN103012399B (zh) 7-氧代吡啶并嘧啶类化合物及其药用组合物和应用
WO2016070816A1 (zh) 嘧啶或吡啶类化合物、其制备方法和医药用途
WO2016026445A1 (zh) 作为fgfr激酶抑制剂的吲唑类化合物及其制备和应用
CN106467541A (zh) 取代喹诺酮类衍生物或其药学上可接受的盐或立体异构体及其药用组合物和应用
ES2660215T3 (es) Potenciador de efecto antitumoral que comprende un compuesto de imidazooxazina
JPWO2015022926A1 (ja) 新規な縮合ピリミジン化合物又はその塩
US11267815B2 (en) Class of amino-substituted nitrogen-containing fused ring compounds, preparation method therefor, and use thereof
KR102426138B1 (ko) ＰＩ3Ｋ, ｍＴＯＲ 저해제로서 융합된 퀴놀린 화합물
ES2911040T3 (es) Nuevos derivados de heteroaril amida como inhibidores selectivos de histona deacetilasa 1 y 2 (HDAC1/2)
JP2016501251A (ja) がんの治療のための新規二環フェニル−ピリジン／ピラジン
CN105705493A (zh) 喹唑啉衍生物、其制备方法、药物组合物和应用
CN102300847A (zh) Ppar激动剂组合物及其使用方法
CN103214481B (zh) 新型咪唑并[1,2-a]吡啶类化合物、其制备方法、包含此类化合物的药物组合物及其用途
CN112313207B (zh) 一种氰基取代吡啶及氰基取代嘧啶类化合物、制备方法及其应用
US9458106B2 (en) Phenyl-pyridine/pyrazine amides for the treatment of cancer
CN103965213A (zh) 7,8-二氢-6H-[1,4]噁嗪[3,2-g]喹唑啉类衍生物及其制备方法和用途
CN103965211A (zh) 含喹唑啉结构的三环类衍生物及其制备方法和用途
WO2023024545A1 (zh) Fgfr4抑制剂、组合物及其在药物制备中的用途
AU2018278283B2 (en) Pyridoquinazoline derivatives useful as protein kinase inhibitors
AU2018278284A1 (en) Carboxylic acid derivatives of pyridoquinazolines useful as protein kinase inhibitors
KR20230163335A (ko) 헤테로아릴 유도체 화합물 및 이의 용도
CN115894381A (zh) 一种2,4,5-三取代嘧啶类化合物及其制备方法和用途
TW202246259A (zh) 吡唑醯胺衍生物

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
EE01 Entry into force of recordation of patent licensing contract

Application publication date: 20190705

Assignee: Shanghai Runshi Pharmaceutical Technology Co., Ltd.

Assignor: Shanghai Institute of Pharmaceutical Research, Chinese Academy of Sciences

Contract record no.: X2019990000139

Denomination of invention: Pyrimidino [5,4-b] indozine or pyrimidino [5,4-b] methotrexate compound, its preparation method and Application

License type: Exclusive License

Record date: 20191024

EE01 Entry into force of recordation of patent licensing contract
GR01 Patent grant
GR01 Patent grant