CN106061975B - 作为抗病毒化合物的吡唑并[1,5-a]嘧啶 - Google Patents
作为抗病毒化合物的吡唑并[1,5-a]嘧啶 Download PDFInfo
- Publication number
- CN106061975B CN106061975B CN201580005612.2A CN201580005612A CN106061975B CN 106061975 B CN106061975 B CN 106061975B CN 201580005612 A CN201580005612 A CN 201580005612A CN 106061975 B CN106061975 B CN 106061975B
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- China
- Prior art keywords
- dimethyl
- dimethoxyphenyl
- amine
- methyl
- pyrimidine
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 163
- 230000000840 anti-viral effect Effects 0.000 title description 4
- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 title description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 230000009385 viral infection Effects 0.000 claims abstract description 9
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 106
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 72
- -1 methoxyl group Chemical group 0.000 claims description 71
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 68
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 63
- 125000001072 heteroaryl group Chemical group 0.000 claims description 58
- 229910052736 halogen Inorganic materials 0.000 claims description 37
- 150000002367 halogens Chemical class 0.000 claims description 36
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 35
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 27
- 125000004429 atom Chemical group 0.000 claims description 26
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 20
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- WPFZGADUIUVTCF-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound NC1=CC=NC2=CC=NN12 WPFZGADUIUVTCF-UHFFFAOYSA-N 0.000 claims description 12
- 208000005155 Picornaviridae Infections Diseases 0.000 claims description 9
- OBSBKQPPLHSZBU-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-n-[(4-methylphenyl)methyl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C(OC)C(OC)=CC=C1C1=C2N=C(C)C=C(NCC=3C=CC(C)=CC=3)N2N=C1C OBSBKQPPLHSZBU-UHFFFAOYSA-N 0.000 claims description 8
- PXKZDAXVXGSGOQ-UHFFFAOYSA-N CC1=CC(N(N1CC2=CC=C(C=C2)Cl)C)C3=CC(=C(C=C3)OC)OC Chemical compound CC1=CC(N(N1CC2=CC=C(C=C2)Cl)C)C3=CC(=C(C=C3)OC)OC PXKZDAXVXGSGOQ-UHFFFAOYSA-N 0.000 claims description 8
- CPGRHQQVAJOSBW-UHFFFAOYSA-N CC1=CC(N(N1CC2=CC=C(C=C2)F)C)C3=CC(=C(C=C3)OC)OC Chemical compound CC1=CC(N(N1CC2=CC=C(C=C2)F)C)C3=CC(=C(C=C3)OC)OC CPGRHQQVAJOSBW-UHFFFAOYSA-N 0.000 claims description 8
- MSXVTSZDDFNPCE-UHFFFAOYSA-N CC1=CC(N(N1CC2=CC=CC=C2)C)C3=CC(=C(C=C3)OC)OC Chemical compound CC1=CC(N(N1CC2=CC=CC=C2)C)C3=CC(=C(C=C3)OC)OC MSXVTSZDDFNPCE-UHFFFAOYSA-N 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- KZNLFTCAGUPSBF-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-n-(pyridin-2-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C(OC)C(OC)=CC=C1C1=C2N=C(C)C=C(NCC=3N=CC=CC=3)N2N=C1C KZNLFTCAGUPSBF-UHFFFAOYSA-N 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 claims description 6
- 230000003612 virological effect Effects 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 4
- LNJMHEJAYSYZKK-UHFFFAOYSA-N 2-methylpyrimidine Chemical compound CC1=NC=CC=N1 LNJMHEJAYSYZKK-UHFFFAOYSA-N 0.000 claims description 3
- RZNHUVAFKGHHQT-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(naphthalen-1-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=CC4=CC=CC=C34)N2N=C1C RZNHUVAFKGHHQT-UHFFFAOYSA-N 0.000 claims description 3
- TXNBLAIOWIQZOL-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[[4-(trifluoromethoxy)phenyl]methyl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(OC(F)(F)F)C=C3)N2N=C1C TXNBLAIOWIQZOL-UHFFFAOYSA-N 0.000 claims description 3
- CBBNIDYFELFWDQ-UHFFFAOYSA-N CC1=CC(N(N1CC2=CC3=C(C=C2)OCO3)C)C4=CC(=C(C=C4)OC)OC Chemical compound CC1=CC(N(N1CC2=CC3=C(C=C2)OCO3)C)C4=CC(=C(C=C4)OC)OC CBBNIDYFELFWDQ-UHFFFAOYSA-N 0.000 claims description 3
- FUJPSMVEWMIQPN-UHFFFAOYSA-N CC1=CC(N(N1CC2=CC=C(C=C2)C(C)(C)C)C)C3=CC(=C(C=C3)OC)OC Chemical compound CC1=CC(N(N1CC2=CC=C(C=C2)C(C)(C)C)C)C3=CC(=C(C=C3)OC)OC FUJPSMVEWMIQPN-UHFFFAOYSA-N 0.000 claims description 3
- XWGXGILFOWGHOE-UHFFFAOYSA-N CC1=CC(N(N1CC2=CC=C(C=C2)OC)C)C3=CC(=C(C=C3)OC)OC Chemical compound CC1=CC(N(N1CC2=CC=C(C=C2)OC)C)C3=CC(=C(C=C3)OC)OC XWGXGILFOWGHOE-UHFFFAOYSA-N 0.000 claims description 3
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 3
- 241001493065 dsRNA viruses Species 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- WSKROKBJLCOYIR-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(pyridin-4-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=NC=C3)N2N=C1C WSKROKBJLCOYIR-UHFFFAOYSA-N 0.000 claims 2
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims 2
- RRTCFFFUTAGOSG-UHFFFAOYSA-N benzene;phenol Chemical compound C1=CC=CC=C1.OC1=CC=CC=C1 RRTCFFFUTAGOSG-UHFFFAOYSA-N 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 89
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 58
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- 239000002585 base Substances 0.000 description 51
- 239000007787 solid Substances 0.000 description 46
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
- 238000004128 high performance liquid chromatography Methods 0.000 description 44
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 42
- 239000000243 solution Substances 0.000 description 42
- 238000005160 1H NMR spectroscopy Methods 0.000 description 41
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- 238000000034 method Methods 0.000 description 36
- 230000002829 reductive effect Effects 0.000 description 29
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 28
- 229910052938 sodium sulfate Inorganic materials 0.000 description 25
- 235000011152 sodium sulphate Nutrition 0.000 description 25
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
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Classifications
-
- 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
- A61K31/495—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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14152202.9 | 2014-01-22 | ||
| EP14152202 | 2014-01-22 | ||
| PCT/EP2015/051177 WO2015110491A2 (en) | 2014-01-22 | 2015-01-21 | Pyrazolo[1,5-a]pyrimidin-7-amine derivatives useful in therapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106061975A CN106061975A (zh) | 2016-10-26 |
| CN106061975B true CN106061975B (zh) | 2019-09-24 |
Family
ID=49989585
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201580005612.2A Active CN106061975B (zh) | 2014-01-22 | 2015-01-21 | 作为抗病毒化合物的吡唑并[1,5-a]嘧啶 |
Country Status (11)
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2770363C2 (ru) | 2017-04-05 | 2022-04-15 | Куровир Аб | Гетероароматические соединения, пригодные в терапии |
| TWI795510B (zh) * | 2018-01-17 | 2023-03-11 | 英商葛蘭素史密斯克藍智慧財產發展有限公司 | PI4KIIIβ抑制劑 |
| CN108727386A (zh) * | 2018-07-16 | 2018-11-02 | 广州医科大学 | 一种吡唑并嘧啶类化合物及其制备方法和用途 |
| KR20210046649A (ko) | 2018-08-21 | 2021-04-28 | 교린 세이야꾸 가부시키 가이샤 | 이환식 헤테로방향환 유도체 |
| WO2020074160A1 (en) | 2018-10-10 | 2020-04-16 | Curovir Ab | Condensed pyrimidine or pyridazine derivatives as antiviral agents |
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| CN109988172B (zh) * | 2019-01-10 | 2020-09-29 | 石家庄学院 | 一种吡唑并[1,5-a]嘧啶类杂环化合物及衍生物的合成方法 |
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| US6313124B1 (en) | 1997-07-23 | 2001-11-06 | Dupont Pharmaceuticals Company | Tetrazine bicyclic compounds |
| CA2379585C (en) * | 1999-09-30 | 2006-06-20 | James W. Darrow | Certain alkylene diamine-substituted pyrazolo[1,5,-a]-1,5-pyrimidines and pyrazolo[1,5-a]-1,3,5-triazines |
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| US7601724B2 (en) | 2002-09-04 | 2009-10-13 | Schering Corporation | Substituted pyrazolo[1,5-a]pyrimidines as protein kinase inhibitors |
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| EP3096762B1 (en) | 2023-06-28 |
| WO2015110491A2 (en) | 2015-07-30 |
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| WO2015110491A3 (en) | 2015-09-17 |
| CA2935658C (en) | 2023-02-21 |
| BR112016016798B1 (pt) | 2022-06-28 |
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