CN110520416A - 多取代吡啶酮类衍生物、其制备方法及其医药用途 - Google Patents
多取代吡啶酮类衍生物、其制备方法及其医药用途 Download PDFInfo
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- CN110520416A CN110520416A CN201880024273.6A CN201880024273A CN110520416A CN 110520416 A CN110520416 A CN 110520416A CN 201880024273 A CN201880024273 A CN 201880024273A CN 110520416 A CN110520416 A CN 110520416A
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- Prior art keywords
- heteroaryl
- aryl
- alkyl
- cycloalkyl
- heterocyclyl
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- 239000003112 inhibitor Substances 0.000 claims abstract description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 207
- 125000000217 alkyl group Chemical group 0.000 claims description 178
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 169
- 125000001072 heteroaryl group Chemical group 0.000 claims description 168
- 125000003118 aryl group Chemical group 0.000 claims description 167
- 239000000203 mixture Substances 0.000 claims description 140
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- 229910052736 halogen Inorganic materials 0.000 claims description 96
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- 125000004043 oxo group Chemical group O=* 0.000 claims description 70
- 125000000304 alkynyl group Chemical group 0.000 claims description 62
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- 125000003342 alkenyl group Chemical group 0.000 claims description 54
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 28
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
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- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 10
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- 238000007112 amidation reaction Methods 0.000 claims description 7
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- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
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- JEVCWSUVFOYBFI-UHFFFAOYSA-N cyanyl Chemical compound N#[C] JEVCWSUVFOYBFI-UHFFFAOYSA-N 0.000 claims 1
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- 125000003396 thiol group Chemical class [H]S* 0.000 claims 1
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- 239000007787 solid Substances 0.000 description 211
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 196
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 165
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 159
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 158
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 158
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 114
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- MKJMTKSTMONLDG-UHFFFAOYSA-N 4H-pyrido[1,2-a]pyrazine-8-carboxamide Chemical compound C1=C2N(CC=N1)C=CC(=C2)C(=O)N MKJMTKSTMONLDG-UHFFFAOYSA-N 0.000 description 86
- 238000005160 1H NMR spectroscopy Methods 0.000 description 82
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- 238000004440 column chromatography Methods 0.000 description 41
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 41
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 39
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
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- YLESNOXZSQMAOX-UHFFFAOYSA-N 3-(4-amino-2,5-difluorophenyl)-5-(3,4-dimethoxyphenyl)pyridin-2-amine Chemical compound COC1=C(C=C(C=C1)C2=CC(=C(N=C2)N)C3=CC(=C(C=C3F)N)F)OC YLESNOXZSQMAOX-UHFFFAOYSA-N 0.000 description 7
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D491/04—Ortho-condensed systems
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Abstract
涉及一种多取代吡啶酮类衍生物、其制备方法及其医药用途。特别地,涉及通式(I)所示的多取代吡啶酮类衍生物、其制备方法、含有该衍生物的药物组合物,以及其作为Axl/c‑MET抑制剂用于治疗癌症的用途。其中通式(I)中的各基团的定义与说明书中的定义相同。
Description
PCT国内申请,说明书已公开。
Claims (22)
- PCT国内申请,权利要求书已公开。
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PCT/CN2018/109969 WO2019080723A1 (zh) | 2017-10-26 | 2018-10-12 | 多取代吡啶酮类衍生物、其制备方法及其医药用途 |
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CN113527332A (zh) * | 2020-04-13 | 2021-10-22 | 南开大学 | 具有生物活性的卡波特韦衍生物及其制备方法和应用 |
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CN112625026B (zh) * | 2019-09-24 | 2022-09-09 | 药捷安康(南京)科技股份有限公司 | Tam家族激酶抑制剂的喹啉衍生物 |
CN112625027B (zh) * | 2019-09-24 | 2022-09-09 | 药捷安康(南京)科技股份有限公司 | 杂环衍生物及其用途 |
CN111233779B (zh) * | 2020-04-02 | 2021-08-20 | 廖文英 | 一种来氟米特的制备方法 |
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CN101005843A (zh) * | 2004-06-28 | 2007-07-25 | 布里斯托尔-迈尔斯·斯奎布公司 | 吡咯并三嗪激酶抑制剂 |
CN101128199A (zh) * | 2004-04-23 | 2008-02-20 | 布里斯托尔-迈尔斯斯奎布公司 | 作为激酶抑制剂的单环杂环 |
WO2011095045A1 (zh) * | 2010-02-03 | 2011-08-11 | 上海源力生物技术有限公司 | 吡啶酮酰胺类衍生物、其制备方法及其在医药上的应用 |
WO2012006960A1 (en) * | 2010-07-14 | 2012-01-19 | Zhejiang Beta Pharma Inc. | NOVEL FUSED HETEROCYCLIC DERIVATIVES USEFUL AS c-MET TYROSINE KINASE INHIBITORS |
WO2012059041A1 (en) * | 2010-11-02 | 2012-05-10 | Centaurus Biopharma Co., Ltd. | Novel 6-arylamino pyridone carboxamide as mek inhibitors |
-
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- 2018-10-12 WO PCT/CN2018/109969 patent/WO2019080723A1/zh active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101128199A (zh) * | 2004-04-23 | 2008-02-20 | 布里斯托尔-迈尔斯斯奎布公司 | 作为激酶抑制剂的单环杂环 |
CN101005843A (zh) * | 2004-06-28 | 2007-07-25 | 布里斯托尔-迈尔斯·斯奎布公司 | 吡咯并三嗪激酶抑制剂 |
WO2011095045A1 (zh) * | 2010-02-03 | 2011-08-11 | 上海源力生物技术有限公司 | 吡啶酮酰胺类衍生物、其制备方法及其在医药上的应用 |
WO2012006960A1 (en) * | 2010-07-14 | 2012-01-19 | Zhejiang Beta Pharma Inc. | NOVEL FUSED HETEROCYCLIC DERIVATIVES USEFUL AS c-MET TYROSINE KINASE INHIBITORS |
WO2012059041A1 (en) * | 2010-11-02 | 2012-05-10 | Centaurus Biopharma Co., Ltd. | Novel 6-arylamino pyridone carboxamide as mek inhibitors |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN113527332A (zh) * | 2020-04-13 | 2021-10-22 | 南开大学 | 具有生物活性的卡波特韦衍生物及其制备方法和应用 |
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