KR20150039832A - 디하이드록시피리미딘 탄산 유도체 및 바이러스성 질환의 치료, 개선 또는 예방에서의 이의 용도 - Google Patents
디하이드록시피리미딘 탄산 유도체 및 바이러스성 질환의 치료, 개선 또는 예방에서의 이의 용도 Download PDFInfo
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- KR20150039832A KR20150039832A KR20157005600A KR20157005600A KR20150039832A KR 20150039832 A KR20150039832 A KR 20150039832A KR 20157005600 A KR20157005600 A KR 20157005600A KR 20157005600 A KR20157005600 A KR 20157005600A KR 20150039832 A KR20150039832 A KR 20150039832A
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- 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
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
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- 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
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- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
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- General Chemical & Material Sciences (AREA)
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- Biotechnology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261679968P | 2012-08-06 | 2012-08-06 | |
| US61/679,968 | 2012-08-06 | ||
| PCT/EP2013/066388 WO2014023691A1 (en) | 2012-08-06 | 2013-08-05 | Dihydroxypyrimidine carbonic acid derivatives and their use in the treatment, amelioration or prevention of a viral disease |
Publications (1)
| Publication Number | Publication Date |
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| KR20150039832A true KR20150039832A (ko) | 2015-04-13 |
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| US (1) | US8921388B2 (https=) |
| EP (1) | EP2885289A1 (https=) |
| JP (1) | JP2015524457A (https=) |
| KR (1) | KR20150039832A (https=) |
| CN (1) | CN104619699A (https=) |
| BR (1) | BR112015002516A2 (https=) |
| CA (1) | CA2879245A1 (https=) |
| HK (2) | HK1211289A1 (https=) |
| MX (1) | MX2015001478A (https=) |
| RU (1) | RU2015107803A (https=) |
| WO (1) | WO2014023691A1 (https=) |
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| US9309250B2 (en) | 2011-06-22 | 2016-04-12 | Vertex Pharmaceuticals Incorporated | Substituted pyrrolo[2,3-b]pyrazines as ATR kinase inhibitors |
| SI2941432T1 (en) | 2012-12-07 | 2018-07-31 | Vertex Pharmaceuticals Incorporated | 2-AMINO-6-FLUORO-N- (5-FLUORO-4- (4- (4- (OXETHAN-3-YL) PIPERAZIN-1-CARBONYL) PIPERIDIN-1-YLIPRIDIN-3-YL) 1,5 ALFA) PYRIMIDINE-3-CARBOXAMIDE AS ATR KINAZE INHIBITOR |
| US8957078B2 (en) | 2013-03-15 | 2015-02-17 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| EP2970288A1 (en) | 2013-03-15 | 2016-01-20 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| WO2014143240A1 (en) | 2013-03-15 | 2014-09-18 | Vertex Pharmaceuticals Incorporated | Fused pyrazolopyrimidine derivatives useful as inhibitors of atr kinase |
| PT3077397T (pt) | 2013-12-06 | 2020-01-22 | Vertex Pharma | Composto de 2-amino-6-fluoro-n-[5-fluoro-piridin-3-il]pirazolo[1,5-a]pirimidin-3-carboxamida útil como inibidor da atr quinase, a sua preparação, diferentes formas sólidas e derivados radiomarcados do mesmo |
| MX373102B (es) | 2014-06-05 | 2020-04-17 | Vertex Pharma | Derivados radiomarcados de un compuesto de 2-amino-6-fluoro-n-[5-fluoro-piridin-3-il]-pirazolo[1,5-a]pirimidin-3-carboxamida útil como inhibidor de ataxia telangiectasia mutada y rad3 relacionado (atr) cinasa, preparación de tal compuesto y diferentes formas sólidas del mismo. |
| SG11201610500WA (en) | 2014-06-17 | 2017-01-27 | Vertex Pharma | Method for treating cancer using a combination of chk1 and atr inhibitors |
| CN107074880A (zh) | 2014-07-07 | 2017-08-18 | 萨维拉制药有限公司 | 二氢吡啶并吡嗪‑1,8‑二酮和它们在治疗、改善或预防病毒疾病中的用途 |
| US10774051B2 (en) * | 2015-04-24 | 2020-09-15 | Shionogi & Co., Ltd. | 6-membered heterocyclic derivatives and pharmaceutical composition comprising the same |
| SG11201708721XA (en) | 2015-04-28 | 2017-11-29 | Shionogi & Co | Substituted polycyclic pyridone derivative and prodrug thereof |
| US20170081331A1 (en) | 2015-09-18 | 2017-03-23 | F. Hoffmann-La Roche Ag | Pyrazolopyrazines and their use in the treatment, amelioration or prevention of a viral disease |
| AU2016331955B2 (en) | 2015-09-30 | 2022-07-21 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of DNA damaging agents and ATR inhibitors |
| EP3374350B1 (en) | 2015-11-09 | 2022-01-05 | Forge Therapeutics, Inc. | Hydroxypyridinone and hydroxypyrimidinone based compounds for treating bacterial infections |
| WO2017083434A1 (en) | 2015-11-09 | 2017-05-18 | Forge Therapeutics, Inc. | Pyrone based compounds for treating bacterial infections |
| SG11201804348SA (en) | 2015-12-15 | 2018-06-28 | Shionogi & Co | Medicine for treating influenza characterized by comprising combination of cap-dependent endonuclease inhibitor with anti-influenza drug |
| WO2018001948A1 (en) * | 2016-06-29 | 2018-01-04 | F. Hoffmann-La Roche Ag | Pyridazinone-based broad spectrum anti-influenza inhibitors |
| KR20190018469A (ko) | 2016-08-10 | 2019-02-22 | 시오노기세야쿠 가부시키가이샤 | 치환된 다환성 피리돈 유도체 및 그의 프로드러그를 함유하는 의약 조성물 |
| JP6692113B2 (ja) * | 2016-10-21 | 2020-05-13 | 塩野義製薬株式会社 | ６員複素環誘導体を含有する医薬組成物 |
| US11021471B2 (en) | 2017-05-10 | 2021-06-01 | Forge Therapeutics, Inc. | Antibacterial compounds |
| SG11202002218VA (en) | 2017-09-15 | 2020-04-29 | Aduro Biotech Inc | Pyrazolopyrimidinone compounds and uses thereof |
| CN109503528B (zh) * | 2018-05-15 | 2022-06-14 | 天津国际生物医药联合研究院 | 一种化合物及其在抗沙粒病毒感染中的应用 |
| AU2019345150A1 (en) | 2018-09-20 | 2021-05-13 | Blacksmith Medicines, Inc. | Antibacterial compounds |
| CN113396149B (zh) | 2018-12-06 | 2024-07-02 | 星座制药公司 | Trex1的调节剂 |
| CN109897007A (zh) * | 2019-02-25 | 2019-06-18 | 天津国际生物医药联合研究院 | 二羟基嘧啶化合物及其应用 |
| WO2021195258A1 (en) * | 2020-03-25 | 2021-09-30 | Forge Therapeutics, Inc. | Lpxc inhibitor, formulations, and uses thereof |
| WO2021195260A1 (en) | 2020-03-25 | 2021-09-30 | Forge Therapeutics, Inc. | Lpxc inhibitor and methods of making |
| CA3191084A1 (en) | 2020-09-09 | 2022-03-17 | Gerald Burke | Formulations of a somatostatin modulator |
| MX2023013045A (es) * | 2021-05-05 | 2024-01-19 | Constellation Pharmaceuticals Inc | Moduladores de exonucleasa i de tres reparaciones principales (trex1). |
| TW202322818A (zh) | 2021-09-28 | 2023-06-16 | 美商福吉醫療公司 | Lpxc抑制劑及其用途 |
| WO2025264724A1 (en) * | 2024-06-20 | 2025-12-26 | The Regents Of The University Of California | Mpro inhibitors and uses thereof |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5475109A (en) | 1994-10-17 | 1995-12-12 | Merck & Co., Inc. | Dioxobutanoic acid derivatives as inhibitors of influenza endonuclease |
| IL161337A0 (en) * | 2001-10-26 | 2004-09-27 | Angeletti P Ist Richerche Bio | N-substituted hydroxypyrimidinone carboxamide inhibitors of hiv integrase |
| ATE355064T1 (de) * | 2001-10-26 | 2006-03-15 | Angeletti P Ist Richerche Bio | Dihydroxypyrimidin-carbonsäueramid-hemmer der hiv-integrase |
| AU2003262946A1 (en) | 2002-08-30 | 2004-03-19 | Pharmacia And Upjohn Company | Method of preventing or treating atherosclerosis or restenosis |
| TW200526635A (en) | 2003-12-22 | 2005-08-16 | Shionogi & Co | Hydroxypyrimidinone derivative having HIV integrase inhibitory activity |
| CN1934093A (zh) * | 2004-01-12 | 2007-03-21 | 吉里德科学公司 | 嘧啶基膦酸酯抗病毒化合物和使用方法 |
| JP4953297B2 (ja) | 2004-09-15 | 2012-06-13 | 塩野義製薬株式会社 | Ｈｉｖインテグラーゼ阻害活性を有するカルバモイルピリドン誘導体 |
| AR057023A1 (es) | 2005-05-16 | 2007-11-14 | Gilead Sciences Inc | Compuestos heterociclicos con propiedades inhibidoras de hiv-integrasa |
| EP2412708A4 (en) | 2009-03-26 | 2014-07-23 | Shionogi & Co | SUBSTITUTED 3-HYDROXY-4-PYRIDONE DERIVATIVE |
| TWI518084B (zh) | 2009-03-26 | 2016-01-21 | 鹽野義製藥股份有限公司 | 哌喃酮與吡啶酮衍生物之製造方法 |
| WO2011000566A2 (en) | 2009-06-30 | 2011-01-06 | Savira Pharmaceuticals Gmbh | Compounds and pharmaceutical compositions for the treatment of negative-sense ssrna virus infections |
| WO2011046920A1 (en) | 2009-10-12 | 2011-04-21 | Baylor College Of Medicine | Novel dxr inhibitors for antimicrobial therapy |
| US20120329842A1 (en) * | 2010-12-23 | 2012-12-27 | Yongcheng Song | Small molecule compounds as broad-spectrum inhibitors of metallo-beta-lactamases |
| US9328075B2 (en) * | 2011-05-05 | 2016-05-03 | St. Jude Children's Research Hospital | Pyrimidinone compounds and methods for treating influenza |
| CN102617487B (zh) * | 2012-03-02 | 2014-04-02 | 北京工业大学 | 多取代嘧啶酮类化合物及其制备方法和应用 |
| CN102911124B (zh) | 2012-10-25 | 2015-11-25 | 山东大学 | 羟基嘧啶酮类化合物及其制备方法与应用 |
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2013
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- 2013-08-05 CN CN201380041462.1A patent/CN104619699A/zh active Pending
- 2013-08-05 WO PCT/EP2013/066388 patent/WO2014023691A1/en not_active Ceased
- 2013-08-05 US US13/958,913 patent/US8921388B2/en not_active Expired - Fee Related
- 2013-08-05 HK HK15112102.3A patent/HK1211289A1/xx unknown
- 2013-08-05 HK HK15111131.0A patent/HK1210177A1/xx unknown
- 2013-08-05 EP EP13759141.8A patent/EP2885289A1/en not_active Withdrawn
- 2013-08-05 MX MX2015001478A patent/MX2015001478A/es unknown
- 2013-08-05 RU RU2015107803A patent/RU2015107803A/ru not_active Application Discontinuation
- 2013-08-05 BR BR112015002516A patent/BR112015002516A2/pt not_active IP Right Cessation
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- 2013-08-05 CA CA2879245A patent/CA2879245A1/en not_active Abandoned
Also Published As
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|---|---|
| WO2014023691A1 (en) | 2014-02-13 |
| CA2879245A1 (en) | 2014-02-13 |
| US20140038990A1 (en) | 2014-02-06 |
| EP2885289A1 (en) | 2015-06-24 |
| JP2015524457A (ja) | 2015-08-24 |
| RU2015107803A (ru) | 2016-09-27 |
| CN104619699A (zh) | 2015-05-13 |
| BR112015002516A2 (pt) | 2017-07-04 |
| HK1210177A1 (en) | 2016-04-15 |
| US8921388B2 (en) | 2014-12-30 |
| HK1211289A1 (en) | 2016-05-20 |
| MX2015001478A (es) | 2015-08-12 |
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