CN104411706A - 咪唑酮类衍生物、其药物组合物和用途 - Google Patents
咪唑酮类衍生物、其药物组合物和用途 Download PDFInfo
- Publication number
- CN104411706A CN104411706A CN201380034055.8A CN201380034055A CN104411706A CN 104411706 A CN104411706 A CN 104411706A CN 201380034055 A CN201380034055 A CN 201380034055A CN 104411706 A CN104411706 A CN 104411706A
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- Prior art keywords
- bases
- quinoline
- methyl
- phenyl
- imidazos
- 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.)
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 14
- WZELXJBMMZFDDU-UHFFFAOYSA-N Imidazol-2-one Chemical class O=C1N=CC=N1 WZELXJBMMZFDDU-UHFFFAOYSA-N 0.000 title abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 239000012453 solvate Substances 0.000 claims abstract description 42
- 239000000651 prodrug Substances 0.000 claims abstract description 30
- 229940002612 prodrug Drugs 0.000 claims abstract description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
- 201000010099 disease Diseases 0.000 claims abstract description 27
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 22
- 208000030159 metabolic disease Diseases 0.000 claims abstract description 7
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 250
- -1 amino, hydroxyl Chemical group 0.000 claims description 171
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 165
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 152
- 150000001875 compounds Chemical class 0.000 claims description 140
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 133
- CFPBYGKISUKURJ-UHFFFAOYSA-N 3h-quinolin-2-one Chemical compound C1=CC=CC2=NC(=O)CC=C21 CFPBYGKISUKURJ-UHFFFAOYSA-N 0.000 claims description 103
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 100
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 81
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 77
- 229910052757 nitrogen Inorganic materials 0.000 claims description 74
- IRFHMTUHTBSEBK-QGZVFWFLSA-N tert-butyl n-[(2s)-2-(2,5-difluorophenyl)-3-quinolin-3-ylpropyl]carbamate Chemical compound C1([C@H](CC=2C=C3C=CC=CC3=NC=2)CNC(=O)OC(C)(C)C)=CC(F)=CC=C1F IRFHMTUHTBSEBK-QGZVFWFLSA-N 0.000 claims description 57
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 49
- AYDQIZKZTQHYIY-UHFFFAOYSA-N OC(=O)C1(C)CC(C(O)=O)=CC=C1 Chemical compound OC(=O)C1(C)CC(C(O)=O)=CC=C1 AYDQIZKZTQHYIY-UHFFFAOYSA-N 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 150000003053 piperidines Chemical class 0.000 claims description 34
- 125000002950 monocyclic group Chemical group 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 150000002367 halogens Chemical class 0.000 claims description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims description 27
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims description 22
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 21
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 18
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 claims description 17
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- 239000001301 oxygen Substances 0.000 claims description 17
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- WITMXBRCQWOZPX-UHFFFAOYSA-N 1-phenylpyrazole Chemical class C1=CC=NN1C1=CC=CC=C1 WITMXBRCQWOZPX-UHFFFAOYSA-N 0.000 claims description 10
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 claims description 8
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- 125000005843 halogen group Chemical group 0.000 claims description 7
- JJWOMLRJNXMLSO-UHFFFAOYSA-N 1-methylsulfonylpiperidine Chemical compound CS(=O)(=O)N1CCCCC1 JJWOMLRJNXMLSO-UHFFFAOYSA-N 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- 239000005864 Sulphur Substances 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 208000016097 disease of metabolism Diseases 0.000 claims description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
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- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 claims description 3
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 3
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- VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical class C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 claims description 2
- KDISMIMTGUMORD-UHFFFAOYSA-N 1-acetylpiperidine Chemical compound CC(=O)N1CCCCC1 KDISMIMTGUMORD-UHFFFAOYSA-N 0.000 claims description 2
- YJLYGWOUDNVDMM-UHFFFAOYSA-N 3-pyrazol-1-ylpyridine Chemical class C1=CC=NN1C1=CC=CN=C1 YJLYGWOUDNVDMM-UHFFFAOYSA-N 0.000 claims description 2
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- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- VIDMOBDFWJRXRT-UHFFFAOYSA-N cyclobutyl(3,6-dihydro-2h-pyridin-1-yl)methanone Chemical compound C1CC=CCN1C(=O)C1CCC1 VIDMOBDFWJRXRT-UHFFFAOYSA-N 0.000 claims description 2
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- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 claims 1
- 206010052399 Neuroendocrine tumour Diseases 0.000 claims 1
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- 208000024172 Cardiovascular disease Diseases 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 666
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
本申请涉及咪唑酮类化合物、其药学可接受的盐、溶剂化物、多晶形物或前药，还涉及包含上述物质的药物组合物和用于预防和治疗蛋白激酶相关性疾病如癌症、代谢疾病、心血管疾病等的用途。
Description
PCT国内申请，说明书已公开。
Claims (1)
- PCT国内申请，权利要求书已公开。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201380034055.8A CN104411706B (zh) | 2012-11-20 | 2013-11-20 | 咪唑酮类衍生物、其药物组合物和用途 |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012104707402 | 2012-11-20 | ||
| CN201210470740.2A CN103833752A (zh) | 2012-11-20 | 2012-11-20 | 咪唑酮并喹啉类衍生物、其药物组合物和用途 |
| CN201380034055.8A CN104411706B (zh) | 2012-11-20 | 2013-11-20 | 咪唑酮类衍生物、其药物组合物和用途 |
| PCT/CN2013/087521 WO2014079364A1 (zh) | 2012-11-20 | 2013-11-20 | 咪唑酮类衍生物、其药物组合物和用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104411706A true CN104411706A (zh) | 2015-03-11 |
| CN104411706B CN104411706B (zh) | 2016-11-16 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210470740.2A Pending CN103833752A (zh) | 2012-11-20 | 2012-11-20 | 咪唑酮并喹啉类衍生物、其药物组合物和用途 |
| CN201380034055.8A Active CN104411706B (zh) | 2012-11-20 | 2013-11-20 | 咪唑酮类衍生物、其药物组合物和用途 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210470740.2A Pending CN103833752A (zh) | 2012-11-20 | 2012-11-20 | 咪唑酮并喹啉类衍生物、其药物组合物和用途 |
Country Status (2)
| Country | Link |
|---|---|
| CN (2) | CN103833752A (zh) |
| WO (1) | WO2014079364A1 (zh) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160264570A1 (en) * | 2013-11-15 | 2016-09-15 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Serv | Method of blocking transmission of malarial parasite |
| JP6290412B2 (ja) * | 2013-11-20 | 2018-03-07 | ベイジン フォーランドファルマ カンパニー リミテッド | イミダゾロン系誘導体、その医薬組成物及び用途 |
| EP2915811A1 (en) * | 2014-03-04 | 2015-09-09 | Centre Régional de Lutte contre le Cancer - Centre François Baclesse | MCL-1 modulating compounds for cancer treatment |
| CN108203404A (zh) * | 2018-03-02 | 2018-06-26 | 上海博邦医药科技有限公司 | (r)-3-苯基哌啶或/和(s)-3-苯基哌啶以及尼拉帕尼的手性中间体的合成方法 |
| CN108440513A (zh) * | 2018-05-16 | 2018-08-24 | 张玉叶 | 一种甲酰胺类衍生物及其在抗肿瘤药物中的应用 |
| CN108440514A (zh) * | 2018-05-16 | 2018-08-24 | 张玉叶 | 一种甲酰胺类衍生物、制备方法及其在抗肿瘤药物中的应用 |
| CN108727355A (zh) * | 2018-05-16 | 2018-11-02 | 张玉叶 | 一种甲酰胺类衍生物、制备方法及其在抗肿瘤药物中的应用 |
| CN108727354A (zh) * | 2018-05-16 | 2018-11-02 | 张玉叶 | 一种甲酰胺类衍生物及其在抗肿瘤药物中的应用 |
| CN108558844A (zh) * | 2018-05-16 | 2018-09-21 | 张玉叶 | 一种甲酰胺类衍生物及其在抗肿瘤药物中的应用 |
| US12115154B2 (en) | 2020-12-16 | 2024-10-15 | Srx Cardio, Llc | Compounds for the modulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101616672A (zh) * | 2007-02-20 | 2009-12-30 | 诺瓦提斯公司 | 作为脂质激酶和mTOR双重抑制剂的咪唑并喹啉类 |
| CN102399218A (zh) * | 2010-09-16 | 2012-04-04 | 和记黄埔医药（上海）有限公司 | 一类并合三杂环及其作为pi3k抑制剂的用途 |
| CN102827160A (zh) * | 2011-06-16 | 2012-12-19 | 上海阳帆医药科技有限公司 | PI3K或PI3K/m-TOR通路抑制剂及其在药学中的用途 |
-
2012
- 2012-11-20 CN CN201210470740.2A patent/CN103833752A/zh active Pending
-
2013
- 2013-11-20 WO PCT/CN2013/087521 patent/WO2014079364A1/zh active Application Filing
- 2013-11-20 CN CN201380034055.8A patent/CN104411706B/zh active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101616672A (zh) * | 2007-02-20 | 2009-12-30 | 诺瓦提斯公司 | 作为脂质激酶和mTOR双重抑制剂的咪唑并喹啉类 |
| CN102399218A (zh) * | 2010-09-16 | 2012-04-04 | 和记黄埔医药（上海）有限公司 | 一类并合三杂环及其作为pi3k抑制剂的用途 |
| CN102827160A (zh) * | 2011-06-16 | 2012-12-19 | 上海阳帆医药科技有限公司 | PI3K或PI3K/m-TOR通路抑制剂及其在药学中的用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104411706B (zh) | 2016-11-16 |
| CN103833752A (zh) | 2014-06-04 |
| WO2014079364A1 (zh) | 2014-05-30 |
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