JP6698693B2 - Ｒｓｖ抗ウイルス性ピラゾロおよびトリアゾロピリミジン化合物 - Google Patents
Ｒｓｖ抗ウイルス性ピラゾロおよびトリアゾロピリミジン化合物 Download PDFInfo
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- JP6698693B2 JP6698693B2 JP2017556537A JP2017556537A JP6698693B2 JP 6698693 B2 JP6698693 B2 JP 6698693B2 JP 2017556537 A JP2017556537 A JP 2017556537A JP 2017556537 A JP2017556537 A JP 2017556537A JP 6698693 B2 JP6698693 B2 JP 6698693B2
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- 230000000840 anti-viral effect Effects 0.000 title description 10
- YWBFPKPWMSWWEA-UHFFFAOYSA-O triazolopyrimidine Chemical class BrC1=CC=CC(C=2N=C3N=CN[N+]3=C(NCC=3C=CN=CC=3)C=2)=C1 YWBFPKPWMSWWEA-UHFFFAOYSA-O 0.000 title description 2
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical compound C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 335
- -1 Hydroxycarbonyl group Chemical group 0.000 claims description 182
- 125000001424 substituent group Chemical group 0.000 claims description 169
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 140
- 125000000217 alkyl group Chemical group 0.000 claims description 134
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 126
- 239000002904 solvent Substances 0.000 claims description 122
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 119
- 238000000034 method Methods 0.000 claims description 99
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 94
- 125000005843 halogen group Chemical group 0.000 claims description 94
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 64
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 58
- 150000003839 salts Chemical class 0.000 claims description 46
- 125000003342 alkenyl group Chemical group 0.000 claims description 45
- 239000002253 acid Substances 0.000 claims description 43
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 43
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 30
- 125000000304 alkynyl group Chemical group 0.000 claims description 27
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 27
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 25
- 125000003277 amino group Chemical group 0.000 claims description 24
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 24
- 125000004076 pyridyl group Chemical group 0.000 claims description 24
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 22
- 125000002393 azetidinyl group Chemical group 0.000 claims description 22
- 125000002883 imidazolyl group Chemical group 0.000 claims description 22
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- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 20
- 125000000335 thiazolyl group Chemical group 0.000 claims description 20
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 16
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- NUXXCAUMTRLOKX-UHFFFAOYSA-N 2-methylpiperidine-1-carbaldehyde Chemical compound CC1CCCCN1C=O NUXXCAUMTRLOKX-UHFFFAOYSA-N 0.000 claims description 12
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- 125000002541 furyl group Chemical group 0.000 claims description 12
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 12
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 12
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- 125000003545 alkoxy group Chemical group 0.000 claims description 11
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
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- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
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- HPYLZSUEFFQHRS-UHFFFAOYSA-N 2h-1,2,4-oxadiazine Chemical compound N1OC=CN=C1 HPYLZSUEFFQHRS-UHFFFAOYSA-N 0.000 claims description 3
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- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000003566 oxetanyl group Chemical group 0.000 claims description 2
- 208000030925 respiratory syncytial virus infectious disease Diseases 0.000 claims 3
- 230000003287 optical effect Effects 0.000 claims 2
- 229940123066 Polymerase inhibitor Drugs 0.000 claims 1
- 229940126187 RSV fusion inhibitor Drugs 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 733
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 95
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
- 239000002244 precipitate Substances 0.000 description 57
- 229910020175 SiOH Inorganic materials 0.000 description 54
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 50
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
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- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 14
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
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- 238000012546 transfer Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- UNNCHYARSNZOPF-UHFFFAOYSA-L way-154641 Chemical compound [Na+].[Na+].NC(=O)CN(CC(N)=O)S(=O)(=O)C1=CC=CC(NC=2N=C(NC=3C=C(C(C=4C(=CC(NC=5N=C(NC=6C=C(C=CC=6)S(=O)(=O)N(CC(N)=O)CC(N)=O)N=C(NC=6C=C(C=CC=6)S(=O)(=O)N(CC(N)=O)CC(N)=O)N=5)=CC=4)S([O-])(=O)=O)=CC=3)S([O-])(=O)=O)N=C(NC=3C=C(C=CC=3)S(=O)(=O)N(CC(N)=O)CC(N)=O)N=2)=C1 UNNCHYARSNZOPF-UHFFFAOYSA-L 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- DUBNHZYBDBBJHD-UHFFFAOYSA-L ziram Chemical compound [Zn+2].CN(C)C([S-])=S.CN(C)C([S-])=S DUBNHZYBDBBJHD-UHFFFAOYSA-L 0.000 description 1
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
- A61K31/16—Amides, e.g. hydroxamic acids
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- A61P31/14—Antivirals for RNA viruses
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562153753P | 2015-04-28 | 2015-04-28 | |
| US62/153,753 | 2015-04-28 | ||
| US201562204390P | 2015-08-12 | 2015-08-12 | |
| US62/204,390 | 2015-08-12 | ||
| PCT/EP2016/059392 WO2016174079A1 (en) | 2015-04-28 | 2016-04-27 | Rsv antiviral pyrazolo- and triazolo-pyrimidine compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018514544A JP2018514544A (ja) | 2018-06-07 |
| JP2018514544A5 JP2018514544A5 (https=) | 2020-02-20 |
| JP6698693B2 true JP6698693B2 (ja) | 2020-05-27 |
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| JP (1) | JP6698693B2 (https=) |
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| CA (1) | CA2981404C (https=) |
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| CY (1) | CY1125329T1 (https=) |
| DK (1) | DK3288942T3 (https=) |
| EA (1) | EA035689B1 (https=) |
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| HU (1) | HUE057626T2 (https=) |
| IL (1) | IL254750B (https=) |
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| MA (1) | MA41974A (https=) |
| MX (1) | MX369040B (https=) |
| PH (1) | PH12017501958B1 (https=) |
| PL (1) | PL3288942T3 (https=) |
| PT (1) | PT3288942T (https=) |
| SG (1) | SG11201708786SA (https=) |
| SI (1) | SI3288942T1 (https=) |
| TW (1) | TWI703146B (https=) |
| UA (1) | UA120448C2 (https=) |
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| ZA (1) | ZA201707320B (https=) |
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| JO3637B1 (ar) * | 2015-04-28 | 2020-08-27 | Janssen Sciences Ireland Uc | مركبات بيرازولو- وترايازولو- بيريميدين مضادة للفيروسات rsv |
| TW201932470A (zh) | 2017-11-29 | 2019-08-16 | 愛爾蘭商健生科學愛爾蘭無限公司 | 具有抗ｒｓｖ活性之吡唑并嘧啶 |
| TW201936193A (zh) * | 2017-12-05 | 2019-09-16 | 愛爾蘭商健生科學愛爾蘭無限公司 | 使用組合產品治療ｒｓｖ |
| SG11202006141RA (en) | 2018-01-31 | 2020-07-29 | Janssen Sciences Ireland Unlimited Co | Cycloalkyl substituted pyrazolopyrimidines having activity against rsv |
| US11708369B2 (en) | 2018-04-23 | 2023-07-25 | Janssen Sciences Ireland Unlimited Company | Heteroaromatic compounds having activity against RSV |
| CA3099311A1 (en) * | 2018-05-03 | 2019-11-07 | Georgia State University Research Foundation, Inc. | Inhibitors of rsv replication and applications thereof |
| EA202191482A1 (ru) * | 2018-11-26 | 2021-12-14 | Янссен Сайенсиз Айрлэнд Анлимитед Компани | Другие гетероароматические соединения, обладающие активностью против rsv |
| JPWO2020138015A1 (ja) | 2018-12-27 | 2021-11-18 | 大正製薬株式会社 | ピラゾロ［１，５−ａ］ピリミジン大環状化合物 |
| EA202193223A1 (ru) | 2019-05-23 | 2022-03-10 | Янссен Сайенсиз Айрлэнд Анлимитед Компани | Другие гетероароматические соединения, действующие против рсв |
| CN111440173B (zh) * | 2020-03-27 | 2021-05-14 | 山东大学 | 一种pi3k抑制剂的制备方法 |
| WO2022020891A1 (en) * | 2020-07-27 | 2022-02-03 | Esfam Biotech Pty Ltd | Methods of prophylaxis and treatment of corona virus |
| WO2022020889A1 (en) * | 2020-07-27 | 2022-02-03 | Esfam Biotech Pty Ltd | Method of treatment of cytomegalovirus |
| CA3200111C (en) | 2020-10-28 | 2025-02-18 | Shionogi & Co., Ltd. | AMIDE DERIVATIVE WITH ANTIVIRAL ACTIVITY |
| CN117120050A (zh) | 2021-02-08 | 2023-11-24 | 纽约哥伦比亚大学董事会 | 用于治疗神经和精神疾病的受氧杂-伊博格碱启发的类似物 |
| CN116425754A (zh) * | 2021-12-30 | 2023-07-14 | 苏州爱科百发生物医药技术有限公司 | 芳杂双环化合物及其抗病毒用途 |
| CA3259556A1 (en) * | 2022-06-17 | 2023-12-21 | Trawsfynydd Therapeutics, Inc. | COMPOUNDS FOR THE TREATMENT OF CORONAVIRUS INFECTION |
| WO2024121264A1 (en) | 2022-12-09 | 2024-06-13 | Syngenta Crop Protection Ag | Insecticidal compound based on pyrazole derivatives |
| WO2024121261A1 (en) | 2022-12-09 | 2024-06-13 | Syngenta Crop Protection Ag | Insecticidal compound based on pyrazole derivatives |
| WO2024121263A1 (en) | 2022-12-09 | 2024-06-13 | Syngenta Crop Protection Ag | Insecticidal compound based on pyrazole derivatives |
| WO2024121262A1 (en) | 2022-12-09 | 2024-06-13 | Syngenta Crop Protection Ag | Insecticidal compound based on pyrazole derivatives |
| WO2026003043A1 (en) * | 2024-06-26 | 2026-01-02 | Janssen Pharmaceutica Nv | Malt1 inhibitors |
| WO2026003049A1 (en) * | 2024-06-26 | 2026-01-02 | Janssen Pharmaceutica Nv | Malt1 inhibitors |
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2016
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