BR112016016798B1 - Composto, composição farmacêutica, e, uso de um composto - Google Patents
Composto, composição farmacêutica, e, uso de um composto Download PDFInfo
- Publication number
- BR112016016798B1 BR112016016798B1 BR112016016798-8A BR112016016798A BR112016016798B1 BR 112016016798 B1 BR112016016798 B1 BR 112016016798B1 BR 112016016798 A BR112016016798 A BR 112016016798A BR 112016016798 B1 BR112016016798 B1 BR 112016016798B1
- Authority
- BR
- Brazil
- Prior art keywords
- pyrimidin
- dimethyl
- pyrazolo
- dimethoxyphenyl
- amine
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 175
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 238000011282 treatment Methods 0.000 claims abstract description 21
- 208000036142 Viral infection Diseases 0.000 claims abstract description 14
- 230000009385 viral infection Effects 0.000 claims abstract description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 68
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 66
- -1 1- oxidopyridin-1-io-4-yl Chemical group 0.000 claims description 43
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 150000002367 halogens Chemical class 0.000 claims description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- 125000004429 atom Chemical group 0.000 claims description 26
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 10
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 10
- 125000002837 carbocyclic group Chemical group 0.000 claims description 9
- 102220431943 c.61C>T Human genes 0.000 claims description 8
- WPFZGADUIUVTCF-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound NC1=CC=NC2=CC=NN12 WPFZGADUIUVTCF-UHFFFAOYSA-N 0.000 claims description 8
- 102200040459 rs3087473 Human genes 0.000 claims description 8
- 102200029950 rs35898499 Human genes 0.000 claims description 8
- TWCYMPJYRKTZKP-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-n-[(4-methoxyphenyl)methyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=CC(OC)=CC=C1CNC1=CC(C)=NC2=C(C=3C=C(OC)C(OC)=CC=3)C(C)=NN12 TWCYMPJYRKTZKP-UHFFFAOYSA-N 0.000 claims description 7
- HBVPEDQMSBLKBA-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C(OC)C(OC)=CC=C1C1=C2N=C(C)C=C(NCC=3C=CC(Cl)=CC=3)N2N=C1C HBVPEDQMSBLKBA-UHFFFAOYSA-N 0.000 claims description 7
- 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 6
- CHFHLLRPKVPRKX-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-n-[(4-fluorophenyl)methyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C(OC)C(OC)=CC=C1C1=C2N=C(C)C=C(NCC=3C=CC(F)=CC=3)N2N=C1C CHFHLLRPKVPRKX-UHFFFAOYSA-N 0.000 claims description 6
- GVNJISSYDZPTMJ-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C(OC)C(OC)=CC=C1C1=C2N=C(C)C=C(NCC=3C=C4OCOC4=CC=3)N2N=C1C GVNJISSYDZPTMJ-UHFFFAOYSA-N 0.000 claims description 6
- DKLSLBVMZJPYMK-UHFFFAOYSA-N n-benzyl-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C(OC)C(OC)=CC=C1C1=C2N=C(C)C=C(NCC=3C=CC=CC=3)N2N=C1C DKLSLBVMZJPYMK-UHFFFAOYSA-N 0.000 claims description 6
- 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 4
- 239000003814 drug Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- PLNYJRAFJKJYPQ-UHFFFAOYSA-N 1-[4-[[[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]phenyl]ethanone Chemical compound COC=1C=C(C=CC1OC)C=1C(=NN2C1N=C(C=C2NCC2=CC=C(C=C2)C(C)=O)C)C PLNYJRAFJKJYPQ-UHFFFAOYSA-N 0.000 claims 2
- 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 2
- HHJZAOCYINMJSK-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[(2-methylpyrimidin-4-yl)methyl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC=1C=C(C=CC1OC)C=1C(=NN2C1N=C(C=C2NCC2=NC(=NC=C2)C)C)C HHJZAOCYINMJSK-UHFFFAOYSA-N 0.000 claims 2
- JBKQNEDBXTWVCM-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[(3-methylsulfonylphenyl)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(=CC=C3)S(C)(=O)=O)N2N=C1C JBKQNEDBXTWVCM-UHFFFAOYSA-N 0.000 claims 2
- XYZQGIPODNTXIL-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[(4-methylsulfonylphenyl)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(C=C3)S(C)(=O)=O)N2N=C1C XYZQGIPODNTXIL-UHFFFAOYSA-N 0.000 claims 2
- YVAZHGJQDDGRFS-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[[4-(trifluoromethyl)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(C=C3)C(F)(F)F)N2N=C1C YVAZHGJQDDGRFS-UHFFFAOYSA-N 0.000 claims 2
- PJVBPZOSKYBCLZ-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-N-[(6-methoxypyridin-3-yl)methyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(C=C2NCC=1C=NC(=CC=1)OC)C)C PJVBPZOSKYBCLZ-UHFFFAOYSA-N 0.000 claims 2
- XNOGISXLVUBYCR-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-N-[[4-(dimethylamino)phenyl]methyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound COC=1C=C(C=CC=1OC)C=1C(=NN2C=1N=C(C=C2NCC1=CC=C(C=C1)N(C)C)C)C XNOGISXLVUBYCR-UHFFFAOYSA-N 0.000 claims 2
- SBUYZGHVERCOOC-UHFFFAOYSA-N 4-[[[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]benzenesulfonamide Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(C=C3)S(N)(=O)=O)N2N=C1C SBUYZGHVERCOOC-UHFFFAOYSA-N 0.000 claims 2
- IFJUQDKQZZQODR-UHFFFAOYSA-N 4-[[[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]phenol Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(O)C=C3)N2N=C1C IFJUQDKQZZQODR-UHFFFAOYSA-N 0.000 claims 2
- VYBBORGOFHDGFX-UHFFFAOYSA-N N-[(4-tert-butylphenyl)methyl]-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C(C)(C)(C)C1=CC=C(C=C1)CNC1=CC(=NC=2N1N=C(C=2C1=CC(=C(C=C1)OC)OC)C)C VYBBORGOFHDGFX-UHFFFAOYSA-N 0.000 claims 2
- FCLOWALYHPZNNC-UHFFFAOYSA-N N-[4-[[[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]phenyl]acetamide Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(NC(C)=O)C=C3)N2N=C1C FCLOWALYHPZNNC-UHFFFAOYSA-N 0.000 claims 2
- UNPTYLLVISAIOS-UHFFFAOYSA-N N-[4-[[[3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]phenyl]methanesulfonamide Chemical compound COC1=C(OC)C=C(C=C1)C1=C2N=C(C)C=C(NCC3=CC=C(NS(C)(=O)=O)C=C3)N2N=C1C UNPTYLLVISAIOS-UHFFFAOYSA-N 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 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 1
- LSKFDIAWFVSIIE-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[(6-methylpyridin-3-yl)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(C)N=C3)N2N=C1C LSKFDIAWFVSIIE-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 18
- 238000002560 therapeutic procedure Methods 0.000 abstract description 5
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- 125000005842 heteroatom Chemical group 0.000 description 27
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
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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
- A61K31/495—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
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- 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
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- 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)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
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- 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)
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| 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 |
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| 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 |
| MY200452A (en) | 2018-08-21 | 2023-12-27 | Kyorin Seiyaku Kk | Bicyclic heteroaromatic ring derivative |
| AU2019359166B2 (en) * | 2018-10-10 | 2024-07-11 | 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 |
| WO2020074160A1 (en) | 2018-10-10 | 2020-04-16 | Curovir Ab | Condensed pyrimidine or pyridazine derivatives as antiviral agents |
| 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 |
| EP4028131B1 (en) | 2019-08-20 | 2023-11-22 | Curovir Ab | Heteroaromatic compounds useful in therapy |
| WO2024184442A1 (en) | 2023-03-09 | 2024-09-12 | Curovir Ab | Compound and formulation for systemic therapy by oral transmucosal administration |
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| US5688949A (en) * | 1991-04-22 | 1997-11-18 | Otsuka Pharmaceutical Factory, Inc. | Pyrazolo 1,5-A!pyrimidine derivatives and anti-inflammatory agent containing the same |
| US6313124B1 (en) | 1997-07-23 | 2001-11-06 | Dupont Pharmaceuticals Company | Tetrazine bicyclic compounds |
| HUP0202678A3 (en) * | 1999-09-30 | 2004-06-28 | Pfizer | Certain alkylene diamine-substituted pyrazolo[1,5,-a]-1,5-pyrimidines and pyrazolo[1,5-a]-1,3,5-triazines, pharmaceutical compositions containing them and their use |
| EP1504004B1 (en) * | 2002-05-10 | 2007-06-27 | SmithKline Beecham Corporation | Substituted pyrazolopyrimidines |
| DE60313872T2 (de) * | 2002-09-04 | 2008-01-17 | Schering Corp. | Pyrazoloä1,5-aüpyrimidine als hemmstoffe cyclin-abhängiger kinasen |
| US7601724B2 (en) * | 2002-09-04 | 2009-10-13 | Schering Corporation | Substituted pyrazolo[1,5-a]pyrimidines as protein kinase inhibitors |
| GB0519957D0 (en) * | 2005-09-30 | 2005-11-09 | Sb Pharmco Inc | Chemical compound |
| WO2010086040A1 (en) * | 2009-01-29 | 2010-08-05 | Biomarin Iga, Ltd. | Pyrazolo-pyrimidines for treatment of duchenne muscular dystrophy |
| BR112012021198B1 (pt) * | 2010-02-26 | 2021-12-14 | Mitsubishi Tanabe Pharma Corporation | Compostos de pirazolopirimidina, composições relacionadas e seu uso como inibidores de pde10 |
| US8633198B1 (en) * | 2011-09-20 | 2014-01-21 | Nant Holdings Ip, Llc | Small molecule inhibitors of influenza A RNA-dependent RNA polymerase |
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| AU2015208205A1 (en) | 2016-08-18 |
| EP3096762C0 (en) | 2023-06-28 |
| CA2935658C (en) | 2023-02-21 |
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| WO2015110491A2 (en) | 2015-07-30 |
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| JP6509238B2 (ja) | 2019-05-08 |
| RU2016134130A (ru) | 2018-02-26 |
| JP2017503830A (ja) | 2017-02-02 |
| EP3096762B1 (en) | 2023-06-28 |
| CN106061975B (zh) | 2019-09-24 |
| CA2935658A1 (en) | 2015-07-30 |
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| ZA201605666B (en) | 2021-01-27 |
| EP3096762A2 (en) | 2016-11-30 |
| US9963455B2 (en) | 2018-05-08 |
| ES2954126T3 (es) | 2023-11-20 |
| US20160318937A1 (en) | 2016-11-03 |
| RU2016134130A3 (enExample) | 2018-08-30 |
| RU2689788C2 (ru) | 2019-05-29 |
| CN106061975A (zh) | 2016-10-26 |
| AU2015208205B2 (en) | 2019-12-05 |
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