KR20190115013A - 헤테로아릴설포닐-치환된 피리딘 및 암의 치료에서 이의 용도 - Google Patents
헤테로아릴설포닐-치환된 피리딘 및 암의 치료에서 이의 용도 Download PDFInfo
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- KR20190115013A KR20190115013A KR1020197024694A KR20197024694A KR20190115013A KR 20190115013 A KR20190115013 A KR 20190115013A KR 1020197024694 A KR1020197024694 A KR 1020197024694A KR 20197024694 A KR20197024694 A KR 20197024694A KR 20190115013 A KR20190115013 A KR 20190115013A
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762455639P | 2017-02-07 | 2017-02-07 | |
| US62/455,639 | 2017-02-07 | ||
| US201762594799P | 2017-12-05 | 2017-12-05 | |
| US62/594,799 | 2017-12-05 | ||
| PCT/GB2018/050343 WO2018146469A1 (en) | 2017-02-07 | 2018-02-07 | Heteroarylsulfonyl-substituted pyridines and their use in the treatment of cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20190115013A true KR20190115013A (ko) | 2019-10-10 |
Family
ID=61226606
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197024694A Ceased KR20190115013A (ko) | 2017-02-07 | 2018-02-07 | 헤테로아릴설포닐-치환된 피리딘 및 암의 치료에서 이의 용도 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US11028067B2 (enExample) |
| EP (1) | EP3580215A1 (enExample) |
| JP (1) | JP2020507625A (enExample) |
| KR (1) | KR20190115013A (enExample) |
| CN (1) | CN110382486A (enExample) |
| AU (1) | AU2018218519B2 (enExample) |
| BR (1) | BR112019016223A2 (enExample) |
| CA (1) | CA3051537A1 (enExample) |
| MA (1) | MA47451A (enExample) |
| MX (1) | MX392000B (enExample) |
| WO (1) | WO2018146469A1 (enExample) |
| ZA (1) | ZA201904967B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| GB201514021D0 (en) | 2015-08-07 | 2015-09-23 | Arner Elias Set Jeno | Novel Pyridines and their use in the treatment of cancer |
| EP3580209A1 (en) | 2017-02-07 | 2019-12-18 | Oblique Therapeutics AB | Heterocyclylsulfonyl-substituted pyridines and their use in the treatment of cancer |
| KR20190115014A (ko) | 2017-02-07 | 2019-10-10 | 오블리크 세러퓨틱스 에이비 | 하이드로카르빌설포닐-치환된 피리딘 및 암의 치료에서 이의 용도 |
| MX2019009356A (es) | 2017-02-07 | 2019-09-19 | Oblique Therapeutics Ab | Sulfinilpiridinas y su uso en el tratamiento del cancer. |
| EP3752151A1 (en) * | 2018-02-12 | 2020-12-23 | Cinda Pharma AB | Thioredoxin reductase inhibitors for use in the treatment of cancer |
| EP3853234B1 (en) | 2018-09-18 | 2025-04-23 | Nikang Therapeutics, Inc. | Fused tricyclic ring derivatives as src homology-2 phosphatase inhibitors |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3064846D1 (en) * | 1979-12-19 | 1983-10-20 | Duphar Int Res | New nitrothiophenes, method of preparing the new compounds, as well as fungicidal and/or bactericidal compositions on the basis of the new compounds |
| US4456469A (en) | 1980-03-07 | 1984-06-26 | E. I. Du Pont De Nemours And Company | Pyridyl sulfone herbicides |
| AU543161B2 (en) | 1980-03-07 | 1985-04-04 | E.I. Du Pont De Nemours And Company | Pyrimidine or s.triazine derivatives |
| US4791127A (en) | 1985-10-07 | 1988-12-13 | Nippon Kayaku Kabushiki Kaisha | Alkanesulfonate derivatives and their use as insecticides, acaricides or nematicides |
| DE3812177A1 (de) | 1988-04-13 | 1989-10-26 | Bayer Ag | 2-phenylsulfinyl-nitro-pyridine, verfahren zu ihrer herstellung und ihre verwendung |
| AU2395095A (en) | 1994-04-29 | 1995-11-29 | G.D. Searle & Co. | Method of using (h+/k+) atpase inhibitors as antiviral agents |
| DE19531148A1 (de) | 1995-08-24 | 1997-02-27 | Basf Ag | Fungizide Pyridin-2-yl-Derivate |
| WO1997008147A1 (de) | 1995-08-24 | 1997-03-06 | Basf Aktiengesellschaft | N-heterocyclische verbindungen, zwischenprodukte für ihre herstellung, sie enthaltende mittel und ihre verwendung zur bekämpfung von schadpilzen |
| WO1998054139A1 (de) | 1997-05-30 | 1998-12-03 | Basf Aktiengesellschaft | Verfahren zur herstellung substituierter thiopyridine |
| US6284923B1 (en) | 1997-08-22 | 2001-09-04 | Tularik Inc | Substituted benzene compounds as antiproliferative and cholesterol lowering action |
| JP2001519345A (ja) | 1997-10-02 | 2001-10-23 | メルク エンド カムパニー インコーポレーテッド | プレニルタンパク質トランスフェラーゼの阻害剤 |
| US6297239B1 (en) | 1997-10-08 | 2001-10-02 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| US6191170B1 (en) | 1998-01-13 | 2001-02-20 | Tularik Inc. | Benzenesulfonamides and benzamides as therapeutic agents |
| SI0930302T1 (en) | 1998-01-16 | 2003-10-31 | F. Hoffmann-La Roche Ag | Benzosulfone derivatives |
| WO2001064642A2 (en) | 2000-02-29 | 2001-09-07 | Cor Therapeutics, Inc. | Benzamides and related inhibitors of factor xa |
| US20030187026A1 (en) | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| WO2003068744A1 (en) | 2002-02-18 | 2003-08-21 | Ishihara Sangyo Kaisha, Ltd. | Pyridine derivatives or salts thereof and cytokine production inhibitors containing the same |
| US20030236287A1 (en) | 2002-05-03 | 2003-12-25 | Piotrowski David W. | Positive allosteric modulators of the nicotinic acetylcholine receptor |
| US7037902B2 (en) | 2002-07-03 | 2006-05-02 | Receptron, Inc. | Affinity small molecules for the EPO receptor |
| WO2005007621A2 (en) | 2003-05-30 | 2005-01-27 | Rigel Pharmaceuticals, Inc. | Ubiquitin ligase inhibitors |
| EA011671B1 (ru) | 2004-06-04 | 2009-04-28 | Арена Фармасьютикалз, Инк. | Замещенные производные арила и гетероарила в качестве модуляторов метаболизма и для профилактики и лечения связанных с ним расстройств |
| US20060019967A1 (en) | 2004-07-21 | 2006-01-26 | Su-Ying Wu | SARS CoV main protease inhibitors |
| GB0426313D0 (en) | 2004-12-01 | 2005-01-05 | Merck Sharp & Dohme | Therapeutic agents |
| WO2006083692A2 (en) | 2005-01-28 | 2006-08-10 | Mount Sinai Schoool Of Medicine | Methods of identifying modulators of bromodomains |
| GB0504828D0 (en) | 2005-03-09 | 2005-04-13 | Merck Sharp & Dohme | Therapeutic agents |
| EP1976495A2 (en) | 2006-01-06 | 2008-10-08 | Aarhus Universitet | Compounds acting on the serotonin transporter |
| EP2019827A1 (en) | 2006-04-28 | 2009-02-04 | Avexa Limited | Integrase inhibitors 3 |
| US20090005422A1 (en) * | 2006-05-22 | 2009-01-01 | Thioredoxin Systems Ab | Bacterial thioredoxin reductase inhibitors and methods for use thereof |
| SG183036A1 (en) | 2007-07-17 | 2012-08-30 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
| CN101723932B (zh) | 2008-10-31 | 2013-11-20 | 北京以岭生物工程技术有限公司 | 硝基吡啶乙烯亚胺化合物、其药物组合物及其制备方法和用途 |
| US9421211B2 (en) * | 2009-05-28 | 2016-08-23 | President And Fellows Of Harvard College | N,N′-diarylurea compounds and N,N′-diarylthiourea compounds as inhibitors of translation initiation |
| CN108752280A (zh) | 2009-08-17 | 2018-11-06 | 纪念斯隆-凯特琳癌症中心 | 热休克蛋白结合化合物、组合物以及其制备和使用方法 |
| EP2535059A4 (en) | 2010-02-10 | 2014-03-12 | Public Univ Corp Yokohama City | USE OF A MSIN3B BINDING COMPOUND FOR SPECIFIC BINDING TO THE NEURONIC RESTRICTIVE SILENCER FACTOR (NRSF) |
| CN102206172B (zh) | 2010-03-30 | 2015-02-25 | 中国医学科学院医药生物技术研究所 | 一组取代双芳基化合物及其制备方法和抗病毒应用 |
| EP2609089A1 (en) | 2010-08-27 | 2013-07-03 | Universität des Saarlandes | Selective 17beta-hydroxysteroid dehydrogenase type 1 inhibitors |
| AU2013216885B2 (en) | 2012-02-10 | 2017-08-03 | The Board Of Regents Of The University Of Texas System | Modulators of exchange proteins directly activated by cAMP (EPACs) |
| JP6393322B2 (ja) | 2013-07-10 | 2018-09-19 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規なキラル窒素−リン配位子及びアルケン類の不斉水素化のためのその使用 |
| CN104672214B (zh) | 2013-12-03 | 2019-04-12 | 上海翰森生物医药科技有限公司 | 具有alk抑制活性的化合物及其制备与用途 |
| CN105503827B (zh) | 2014-10-11 | 2019-09-24 | 上海翰森生物医药科技有限公司 | Egfr抑制剂及其制备方法和用途 |
| CN104987324B (zh) | 2015-06-04 | 2018-05-04 | 湖北生物医药产业技术研究院有限公司 | 作为alk抑制剂的嘧啶衍生物 |
| CN105085483B (zh) | 2015-06-04 | 2019-01-01 | 湖北生物医药产业技术研究院有限公司 | 激酶抑制剂及其应用 |
| GB201514021D0 (en) | 2015-08-07 | 2015-09-23 | Arner Elias Set Jeno | Novel Pyridines and their use in the treatment of cancer |
| MX2019009356A (es) | 2017-02-07 | 2019-09-19 | Oblique Therapeutics Ab | Sulfinilpiridinas y su uso en el tratamiento del cancer. |
| KR20190115014A (ko) | 2017-02-07 | 2019-10-10 | 오블리크 세러퓨틱스 에이비 | 하이드로카르빌설포닐-치환된 피리딘 및 암의 치료에서 이의 용도 |
| EP3580209A1 (en) | 2017-02-07 | 2019-12-18 | Oblique Therapeutics AB | Heterocyclylsulfonyl-substituted pyridines and their use in the treatment of cancer |
-
2018
- 2018-02-07 BR BR112019016223A patent/BR112019016223A2/pt not_active IP Right Cessation
- 2018-02-07 JP JP2019563697A patent/JP2020507625A/ja active Pending
- 2018-02-07 CA CA3051537A patent/CA3051537A1/en active Pending
- 2018-02-07 MA MA047451A patent/MA47451A/fr unknown
- 2018-02-07 WO PCT/GB2018/050343 patent/WO2018146469A1/en not_active Ceased
- 2018-02-07 MX MX2019009351A patent/MX392000B/es unknown
- 2018-02-07 US US16/484,039 patent/US11028067B2/en not_active Expired - Fee Related
- 2018-02-07 CN CN201880010198.8A patent/CN110382486A/zh active Pending
- 2018-02-07 AU AU2018218519A patent/AU2018218519B2/en not_active Ceased
- 2018-02-07 KR KR1020197024694A patent/KR20190115013A/ko not_active Ceased
- 2018-02-07 EP EP18705461.4A patent/EP3580215A1/en not_active Withdrawn
-
2019
- 2019-07-29 ZA ZA2019/04967A patent/ZA201904967B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RU2019128045A (ru) | 2021-03-09 |
| JP2020507625A (ja) | 2020-03-12 |
| EP3580215A1 (en) | 2019-12-18 |
| US11028067B2 (en) | 2021-06-08 |
| AU2018218519A1 (en) | 2019-08-15 |
| AU2018218519B2 (en) | 2021-08-05 |
| ZA201904967B (en) | 2023-12-20 |
| WO2018146469A1 (en) | 2018-08-16 |
| BR112019016223A2 (pt) | 2020-04-07 |
| RU2019128045A3 (enExample) | 2021-03-09 |
| CN110382486A (zh) | 2019-10-25 |
| MX392000B (es) | 2025-03-21 |
| MA47451A (fr) | 2019-12-18 |
| US20200223819A1 (en) | 2020-07-16 |
| MX2019009351A (es) | 2019-09-19 |
| CA3051537A1 (en) | 2018-08-16 |
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