JP6689299B2 - 療法に有用なピラゾロ［１，５−ａ］トリアジン−４−アミン誘導体 - Google Patents
療法に有用なピラゾロ［１，５−ａ］トリアジン−４−アミン誘導体 Download PDFInfo
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- JP6689299B2 JP6689299B2 JP2017566742A JP2017566742A JP6689299B2 JP 6689299 B2 JP6689299 B2 JP 6689299B2 JP 2017566742 A JP2017566742 A JP 2017566742A JP 2017566742 A JP2017566742 A JP 2017566742A JP 6689299 B2 JP6689299 B2 JP 6689299B2
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- JP
- Japan
- Prior art keywords
- pyrazolo
- dimethoxyphenyl
- dimethyl
- methyl
- triazin
- 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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- 238000002560 therapeutic procedure Methods 0.000 title claims description 6
- QQOWHRYOXYEMTL-UHFFFAOYSA-N triazin-4-amine Chemical class N=C1C=CN=NN1 QQOWHRYOXYEMTL-UHFFFAOYSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 104
- 150000003839 salts Chemical class 0.000 claims description 56
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 150000002367 halogens Chemical class 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- 125000004429 atom Chemical group 0.000 claims description 25
- -1 R 2 O Chemical class 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 21
- 208000036142 Viral infection Diseases 0.000 claims description 16
- 230000009385 viral infection Effects 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000002837 carbocyclic group Chemical group 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 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 5
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- SZUXYYIDZMHWDD-UHFFFAOYSA-N pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound NC1=NC=NC2=CC=NN12 SZUXYYIDZMHWDD-UHFFFAOYSA-N 0.000 claims description 3
- FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 claims description 2
- JXBSPQSHTHRAGH-UHFFFAOYSA-N 4-[[[8-(3,4-dimethoxyphenyl)-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4-yl]amino]methyl]benzenesulfonamide Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=CC=C(C=C1)S(=O)(=O)N)C)C JXBSPQSHTHRAGH-UHFFFAOYSA-N 0.000 claims description 2
- HDHREEXDABMYCS-UHFFFAOYSA-N 4-[[[8-(3,4-dimethoxyphenyl)-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4-yl]amino]methyl]phenol Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=CC=C(C=C1)O)C)C HDHREEXDABMYCS-UHFFFAOYSA-N 0.000 claims description 2
- PRNLFPBWUWLDJV-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-(1,3-oxazol-5-ylmethyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=CN=CO1)C)C PRNLFPBWUWLDJV-UHFFFAOYSA-N 0.000 claims description 2
- AYAIKIJARAEZJD-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-(pyridazin-4-ylmethyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=CN=NC=C1)C)C AYAIKIJARAEZJD-UHFFFAOYSA-N 0.000 claims description 2
- DCEXCAWOIZVMBX-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-(pyridin-2-ylmethyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=NC=CC=C1)C)C DCEXCAWOIZVMBX-UHFFFAOYSA-N 0.000 claims description 2
- ANMDHEUWJCCQAZ-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-(pyridin-3-ylmethyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC=1C=NC=CC=1)C)C ANMDHEUWJCCQAZ-UHFFFAOYSA-N 0.000 claims description 2
- XVAMGYPWYKSSTH-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-(pyridin-4-ylmethyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=CC=NC=C1)C)C XVAMGYPWYKSSTH-UHFFFAOYSA-N 0.000 claims description 2
- VXBXOHQZDUTAPG-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-(thiophen-2-ylmethyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC=1SC=CC=1)C)C VXBXOHQZDUTAPG-UHFFFAOYSA-N 0.000 claims description 2
- LALVTGVFZZVMLK-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-[(1-methylpyrazol-3-yl)methyl]pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=NN(C=C1)C)C)C LALVTGVFZZVMLK-UHFFFAOYSA-N 0.000 claims description 2
- JUGLNQNKEZDSTD-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-[(3-methylsulfonylphenyl)methyl]pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=CC(=CC=C1)S(=O)(=O)C)C)C JUGLNQNKEZDSTD-UHFFFAOYSA-N 0.000 claims description 2
- RVEJJJXIHUZYRR-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-[(4-methylphenyl)methyl]pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=CC=C(C=C1)C)C)C RVEJJJXIHUZYRR-UHFFFAOYSA-N 0.000 claims description 2
- QEENGCVMZHAIJZ-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-[(4-propan-2-ylphenyl)methyl]pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=CC=C(C=C1)C(C)C)C)C QEENGCVMZHAIJZ-UHFFFAOYSA-N 0.000 claims description 2
- SHFBYFWCOJWEDG-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-[(5-methylfuran-2-yl)methyl]pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC=1OC(=CC=1)C)C)C SHFBYFWCOJWEDG-UHFFFAOYSA-N 0.000 claims description 2
- LHWQEHXXOSSRJS-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-2,7-dimethyl-N-[[4-(trifluoromethyl)phenyl]methyl]pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=CC=C(C=C1)C(F)(F)F)C)C LHWQEHXXOSSRJS-UHFFFAOYSA-N 0.000 claims description 2
- XASLRXHABIHKDP-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-N-[(4-fluorophenyl)methyl]-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=CC=C(C=C1)F)C)C XASLRXHABIHKDP-UHFFFAOYSA-N 0.000 claims description 2
- LYRKQTFOBNEDJK-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-N-[(4-methoxyphenyl)methyl]-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC1=CC=C(C=C1)OC)C)C LYRKQTFOBNEDJK-UHFFFAOYSA-N 0.000 claims description 2
- XIUBDGVYFBEYCJ-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-N-[(6-methoxypyridin-3-yl)methyl]-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(N=C2NCC=1C=NC(=CC=1)OC)C)C XIUBDGVYFBEYCJ-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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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
- 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)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
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| EP15173687.3 | 2015-06-24 | ||
| EP15173687 | 2015-06-24 | ||
| PCT/EP2016/063383 WO2016206999A1 (en) | 2015-06-24 | 2016-06-10 | Pyrazolo[1,5-a]triazin-4-amine derivatives useful in therapy |
Publications (3)
| Publication Number | Publication Date |
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| JP2018522861A JP2018522861A (ja) | 2018-08-16 |
| JP2018522861A5 JP2018522861A5 (enExample) | 2019-07-11 |
| JP6689299B2 true JP6689299B2 (ja) | 2020-04-28 |
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| US (1) | US10407429B2 (enExample) |
| EP (1) | EP3313842B1 (enExample) |
| JP (1) | JP6689299B2 (enExample) |
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| AU (1) | AU2016284638B2 (enExample) |
| BR (1) | BR112017026061B1 (enExample) |
| CA (1) | CA2989722C (enExample) |
| RU (1) | RU2712196C2 (enExample) |
| WO (1) | WO2016206999A1 (enExample) |
| ZA (1) | ZA201800485B (enExample) |
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| WO2017147526A1 (en) | 2016-02-26 | 2017-08-31 | The Board Of Trustees Of The Leland Stanford Junior University | Pi-kinase inhibitors with anti-infective activity |
| CN110520424B (zh) * | 2017-04-05 | 2022-06-21 | 库洛维公司 | 用于疗法的杂芳族化合物 |
| 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 |
| CN118084937A (zh) | 2018-08-21 | 2024-05-28 | 杏林制药株式会社 | 双环杂芳族环衍生物 |
| WO2020074160A1 (en) | 2018-10-10 | 2020-04-16 | Curovir Ab | Condensed pyrimidine or pyridazine derivatives as antiviral agents |
| US12319696B2 (en) * | 2018-10-10 | 2025-06-03 | Curovir Ab | 2,6-dimethyl-n-((pyridin-4-yl)methyl)imidazo[1,2-b]pyridazin-8-amine and 2,5-dimethyl-n-[(pyridin-4-yl)methyl]pyrazolo[1,5-a]pyrimidin-7-amine derivatives for treating viral infections |
| WO2020146657A1 (en) * | 2019-01-11 | 2020-07-16 | The Board Of Trustees Of The Leland Stanford Junior University | Pi4-kinase inhibitors with anti-cancer activity |
| CN114174275A (zh) | 2019-03-21 | 2022-03-11 | 小利兰·斯坦福大学托管委员会 | Pi4-激酶抑制剂及其使用方法 |
| WO2021032611A1 (en) | 2019-08-20 | 2021-02-25 | Curovir Ab | Heteroaromatic compounds useful in therapy |
| CN113801119B (zh) * | 2021-08-30 | 2022-09-30 | 新乡医学院 | 一种吡唑并[1,3,5]三嗪类化合物的合成方法 |
| WO2024184442A1 (en) | 2023-03-09 | 2024-09-12 | Curovir Ab | Compound and formulation for systemic therapy by oral transmucosal administration |
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| US6313124B1 (en) * | 1997-07-23 | 2001-11-06 | Dupont Pharmaceuticals Company | Tetrazine bicyclic compounds |
| US6191131B1 (en) * | 1997-07-23 | 2001-02-20 | Dupont Pharmaceuticals Company | Azolo triazines and pyrimidines |
| ATE301657T1 (de) * | 1998-01-28 | 2005-08-15 | Bristol Myers Squibb Pharma Co | Azolo-pyrimidine |
| US6372743B1 (en) * | 1999-09-30 | 2002-04-16 | Neurogen Corporation | Certain alkylene diamine-substituted pyrazlo (1,5-a)-1,5-pyrimidines and pyrazolo (1,5-a) 1,3,5-triazines |
| GB0716292D0 (en) * | 2007-08-21 | 2007-09-26 | Biofocus Dpi Ltd | Imidazopyrazine compounds |
| FR2943058B1 (fr) | 2009-03-11 | 2011-06-03 | Centre Nat Rech Scient | Derives de pyrazolo°1,5-a!-1,3,5-triazines, leur preparation et leur application en therapeutique. |
| US8633198B1 (en) * | 2011-09-20 | 2014-01-21 | Nant Holdings Ip, Llc | Small molecule inhibitors of influenza A RNA-dependent RNA polymerase |
| EP2634190A1 (en) * | 2012-03-01 | 2013-09-04 | Lead Discovery Center GmbH | Pyrazolo-triazine derivatives as selective cyclin-dependent kinase inhinitors |
| EP2634189A1 (en) | 2012-03-01 | 2013-09-04 | Lead Discovery Center GmbH | Pyrazolo-triazine derivatives as selective cyclin-dependent kinase inhibitors |
| US9573954B2 (en) * | 2012-11-16 | 2017-02-21 | University Health Network | Pyrazolopyrimidine compounds |
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| CA2989722C (en) | 2023-09-19 |
| CA2989722A1 (en) | 2016-12-29 |
| CN107949563A (zh) | 2018-04-20 |
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