CN113166110A - 2-氨基嘧啶类化合物及其应用 - Google Patents

2-氨基嘧啶类化合物及其应用 Download PDF

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CN113166110A
CN113166110A CN201980077663.4A CN201980077663A CN113166110A CN 113166110 A CN113166110 A CN 113166110A CN 201980077663 A CN201980077663 A CN 201980077663A CN 113166110 A CN113166110 A CN 113166110A
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halogen
pharmaceutically acceptable
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CN113166110B (zh
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丁克
丁健
陆小云
耿美玉
李姗
谢华
陈灏
童林江
任小梅
冯芳
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Shanghai Institute of Materia Medica of CAS
Jinan University
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Jinan University
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    • 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
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    • 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
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • 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
    • 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
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    • C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
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    • 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
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Abstract

本发明涉及一种2‑氨基嘧啶类化合物及其应用。该2‑氨基嘧啶类化合物的结构如I所示，该类化合物可以有效抑制EGFR蛋白激酶耐药突变体(如EGFRT790M和EGFRT790M/C797S)的活性，并可以克服现有第三代选择性EGFRT790M小分子抑制剂Osimertinib(AZD9291)，Olmutinib(HM6171)，Rociletinib(CO‑1686)等诱发的非小细胞肺癌等肿瘤病人的临床耐药。

Description

PCT国内申请，说明书已公开。

Claims (24)

  1. PCT国内申请，权利要求书已公开。
CN201980077663.4A 2018-12-12 2019-12-11 2-氨基嘧啶类化合物及其应用 Active CN113166110B (zh)

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CN201811517594 2018-12-12
CN2018115175948 2018-12-12
PCT/CN2019/124686 WO2020119739A1 (zh) 2018-12-12 2019-12-11 2-氨基嘧啶类化合物及其应用

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112292378A (zh) * 2019-05-22 2021-01-29 上海翰森生物医药科技有限公司 含吲哚类衍生物抑制剂、其制备方法和应用
WO2023068858A1 (en) * 2021-10-20 2023-04-27 Hanmi Pharm. Co., Ltd. Therapeutically effective combination of a flt3 inhibitor and a bcl-2 inhibitor for the treatment of acute myeloid leukemia
WO2024087419A1 (zh) * 2022-10-28 2024-05-02 浙大城市学院 一种含氮杂环的硼酸化合物及制备方法和应用

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20200131246A (ko) 2018-02-15 2020-11-23 누베이션 바이오 인크. 키나제 억제제로서의 헤테로시클릭 화합물
CN113264920B (zh) * 2021-05-10 2022-09-02 中国药科大学 一种嘧啶苯并六元环母核的cdk6抑制剂及其制备方法和应用
EP4371983A4 (en) * 2021-07-13 2024-10-09 Korea Res Inst Chemical Tech NOVEL PYRIMIDINE-2,4-DIAMINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITION CONTAINING THEM AS ACTIVE INGREDIENT FOR THE PREVENTION OR TREATMENT OF CANCER

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060183900A1 (en) * 2004-10-29 2006-08-17 Shenlin Huang Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders
US20100105655A1 (en) * 2008-10-29 2010-04-29 Astrazeneca Ab Novel compounds 515
CN101723936A (zh) * 2008-10-27 2010-06-09 上海睿星基因技术有限公司 激酶抑制剂及其在药学中的用途
US20100267707A1 (en) * 2006-06-22 2010-10-21 Merck Sharp & Dohme Corp. Tyrosine Kinase Inhibitors
CN105085489A (zh) * 2014-11-05 2015-11-25 上海页岩科技有限公司 嘧啶或吡啶类化合物、其制备方法和医药用途
US20170121326A1 (en) * 2015-10-28 2017-05-04 Northwestern University Substituted aromatic n-heterocyclic compounds as inhibitors of mitogen-activated protein kinase interacting kinase 1 (mnk1) and 2 (mnk2)
WO2017200016A1 (ja) * 2016-05-17 2017-11-23 公益財団法人がん研究会 Ｅｇｆｒ－ｔｋｉ耐性を獲得した肺癌の治療薬
CN107382974A (zh) * 2017-06-08 2017-11-24 扬州市三药制药有限公司 一种嘧啶胺类化合物作为周期蛋白依赖性激酶4/6抑制剂的应用
WO2019190259A1 (ko) * 2018-03-30 2019-10-03 한미약품 주식회사 상피세포 성장인자 수용체 돌연변이 저해 효과를 갖는 신규 설폰아마이드 유도체

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060183900A1 (en) * 2004-10-29 2006-08-17 Shenlin Huang Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders
US20100267707A1 (en) * 2006-06-22 2010-10-21 Merck Sharp & Dohme Corp. Tyrosine Kinase Inhibitors
CN101723936A (zh) * 2008-10-27 2010-06-09 上海睿星基因技术有限公司 激酶抑制剂及其在药学中的用途
US20100105655A1 (en) * 2008-10-29 2010-04-29 Astrazeneca Ab Novel compounds 515
CN105085489A (zh) * 2014-11-05 2015-11-25 上海页岩科技有限公司 嘧啶或吡啶类化合物、其制备方法和医药用途
US20170121326A1 (en) * 2015-10-28 2017-05-04 Northwestern University Substituted aromatic n-heterocyclic compounds as inhibitors of mitogen-activated protein kinase interacting kinase 1 (mnk1) and 2 (mnk2)
WO2017200016A1 (ja) * 2016-05-17 2017-11-23 公益財団法人がん研究会 Ｅｇｆｒ－ｔｋｉ耐性を獲得した肺癌の治療薬
CN107382974A (zh) * 2017-06-08 2017-11-24 扬州市三药制药有限公司 一种嘧啶胺类化合物作为周期蛋白依赖性激酶4/6抑制剂的应用
WO2019190259A1 (ko) * 2018-03-30 2019-10-03 한미약품 주식회사 상피세포 성장인자 수용체 돌연변이 저해 효과를 갖는 신규 설폰아마이드 유도체

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ACS: "RN1335498-99-1", 《STN》 *
R.B.西尔弗曼编，郭宗儒主译: "《有机药物化学》", 31 January 2008, 化学工业出版社 生物•医药出版分社 *
平丽红等编: "《实用治疗药物学》", 31 March 2018 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112292378A (zh) * 2019-05-22 2021-01-29 上海翰森生物医药科技有限公司 含吲哚类衍生物抑制剂、其制备方法和应用
CN112292378B (zh) * 2019-05-22 2024-02-06 上海翰森生物医药科技有限公司 含吲哚类衍生物抑制剂、其制备方法和应用
WO2023068858A1 (en) * 2021-10-20 2023-04-27 Hanmi Pharm. Co., Ltd. Therapeutically effective combination of a flt3 inhibitor and a bcl-2 inhibitor for the treatment of acute myeloid leukemia
WO2024087419A1 (zh) * 2022-10-28 2024-05-02 浙大城市学院 一种含氮杂环的硼酸化合物及制备方法和应用

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