CN110869371A - 7-位取代吡咯并三嗪类化合物或其药学上可用的盐，及其制备方法和用途 - Google Patents

7-位取代吡咯并三嗪类化合物或其药学上可用的盐，及其制备方法和用途 Download PDF

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CN110869371A
CN110869371A CN201880042091.1A CN201880042091A CN110869371A CN 110869371 A CN110869371 A CN 110869371A CN 201880042091 A CN201880042091 A CN 201880042091A CN 110869371 A CN110869371 A CN 110869371A
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alkyl
substituted
substituent
unsubstituted
pharmaceutically acceptable
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CN110869371B (zh
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杨春皓
蒙凌华
向皞月
李京
张希
王祥
谭村
贺茜
丁健
陈奕
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Shanghai Institute of Materia Medica of CAS
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    • 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
    • C07D487/02—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 two hetero rings
    • C07D487/04—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
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • 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
    • 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
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

本发明涉7‑位取代吡咯[2,1‑f][1,2,4]并三嗪类化合物或其药学上可用的盐，及其制备方法和用途。该类化合物显示较好的PI3K抑制活性，能有效地抑制PI3K激酶活性，并且由于7‑位基团的引入，生物利用度等药代动力学性质有较大提高和改善；此外，本发明中的化合物表现出了对PI3Kδ不可预期的高选择性和强抑制活性，因此这些化合物能用来治疗与PI3K通道相关的疾病，尤其是用来抗癌或者治疗肿瘤、白血病及自身免疫性疾病。经过进一步的优化和筛选后，有望研发成为新型的抗肿瘤药物。

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。
CN201880042091.1A 2017-06-23 2018-06-22 7-位取代吡咯并三嗪类化合物或其药学上可用的盐，及其制备方法和用途 Active CN110869371B (zh)

Applications Claiming Priority (3)

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CN2017104934112 2017-06-23
CN201710493411.2A CN109111447A (zh) 2017-06-23 2017-06-23 7-位取代吡咯并三嗪类化合物或其药学上可用的盐，及其制备方法和用途
PCT/CN2018/092419 WO2018233684A1 (zh) 2017-06-23 2018-06-22 7-位取代吡咯并三嗪类化合物或其药学上可用的盐，及其制备方法和用途

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CN110869371A true CN110869371A (zh) 2020-03-06
CN110869371B CN110869371B (zh) 2022-04-15

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CN201880042091.1A Active CN110869371B (zh) 2017-06-23 2018-06-22 7-位取代吡咯并三嗪类化合物或其药学上可用的盐，及其制备方法和用途

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US (1) US11214572B2 (zh)
EP (1) EP3643717B1 (zh)
JP (1) JP6852199B2 (zh)
KR (1) KR102413943B1 (zh)
CN (2) CN109111447A (zh)
AU (1) AU2018287971B9 (zh)
BR (1) BR112019027545A2 (zh)
CA (1) CA3068114C (zh)
ES (1) ES2887629T3 (zh)
PT (1) PT3643717T (zh)
RU (1) RU2745548C1 (zh)
SG (1) SG11201912827TA (zh)
WO (1) WO2018233684A1 (zh)

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MX2022003217A (es) * 2019-09-19 2022-06-29 Totus Medicines Inc Conjugados terapeuticos.
CN111909153B (zh) * 2020-04-16 2021-11-19 山东鲁西药业有限公司 7-碘吡咯并[2,1-f][1,2,4]三嗪-4-胺的合成工艺

Citations (2)

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Publication number Priority date Publication date Assignee Title
CN102675323A (zh) * 2012-06-01 2012-09-19 南京药石药物研发有限公司 吡咯并[2,1-f][1,2,4]三嗪衍生物及其抗肿瘤用途
CN103450204A (zh) * 2012-05-31 2013-12-18 中国科学院上海药物研究所 吡咯[2，1-f][1，2，4]并三嗪类化合物，其制备方法及用途

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DK1761540T3 (en) 2004-05-13 2016-11-21 Icos Corp Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase DELTA
SG175708A1 (en) 2009-05-27 2011-12-29 Genentech Inc Bicyclic pyrimidine pi3k inhibitor compounds selective for p110 delta, and methods of use
AU2012280508A1 (en) 2011-07-01 2013-12-12 Bayer Intellectual Property Gmbh Hydroxymethylaryl-substituted pyrrolotriazines as ALK1 inhibitors
AR091315A1 (es) 2012-03-06 2015-01-28 Boehringer Ingelheim Int Inhibidores de benzodioxano de la produccion de leucotrieno
MA37975B2 (fr) 2012-09-11 2021-03-31 Genzyme Corp Inhibiteurs de synthase de glucosylcéramide
JP6441910B2 (ja) 2013-09-30 2018-12-19 シャンハイ インリ ファーマシューティカル カンパニー リミティド 縮合ピリミジン化合物、中間体、その調製方法、組成物及び使用
CN109641909B (zh) * 2016-06-25 2022-01-11 苏州开拓药业股份有限公司 雷帕霉素信号通路抑制剂的机理靶标及其治疗应用

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CN103450204A (zh) * 2012-05-31 2013-12-18 中国科学院上海药物研究所 吡咯[2，1-f][1，2，4]并三嗪类化合物，其制备方法及用途
CN102675323A (zh) * 2012-06-01 2012-09-19 南京药石药物研发有限公司 吡咯并[2,1-f][1,2,4]三嗪衍生物及其抗肿瘤用途

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CN109111447A (zh) 2019-01-01
EP3643717A1 (en) 2020-04-29
AU2018287971B8 (en) 2021-02-04
BR112019027545A2 (pt) 2020-07-07
JP6852199B2 (ja) 2021-03-31
US11214572B2 (en) 2022-01-04
US20200157110A1 (en) 2020-05-21
CA3068114A1 (en) 2018-12-27
AU2018287971B9 (en) 2021-02-11
CN110869371B (zh) 2022-04-15
RU2745548C1 (ru) 2021-03-26
PT3643717T (pt) 2021-08-31
EP3643717A4 (en) 2020-04-29
KR102413943B1 (ko) 2022-06-27
AU2018287971A8 (en) 2021-02-04
AU2018287971B2 (en) 2020-12-24
JP2020527541A (ja) 2020-09-10
CA3068114C (en) 2022-05-10
SG11201912827TA (en) 2020-01-30
ES2887629T3 (es) 2021-12-23
KR20200015786A (ko) 2020-02-12
AU2018287971A1 (en) 2020-02-13
WO2018233684A1 (zh) 2018-12-27
EP3643717B1 (en) 2021-06-02

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