JP6803923B2 - 金属酵素阻害化合物 - Google Patents
金属酵素阻害化合物 Download PDFInfo
- Publication number
- JP6803923B2 JP6803923B2 JP2018553846A JP2018553846A JP6803923B2 JP 6803923 B2 JP6803923 B2 JP 6803923B2 JP 2018553846 A JP2018553846 A JP 2018553846A JP 2018553846 A JP2018553846 A JP 2018553846A JP 6803923 B2 JP6803923 B2 JP 6803923B2
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- pyridine
- difluoro
- piperazin
- difluorophenyl
- 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.)
- Expired - Fee Related
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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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61P31/10—Antimycotics
-
- 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
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562273167P | 2015-12-30 | 2015-12-30 | |
| US62/273,167 | 2015-12-30 | ||
| PCT/US2016/069217 WO2017117393A1 (en) | 2015-12-30 | 2016-12-29 | Metalloenzyme inhibitor compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019502755A JP2019502755A (ja) | 2019-01-31 |
| JP2019502755A5 JP2019502755A5 (enExample) | 2019-08-15 |
| JP6803923B2 true JP6803923B2 (ja) | 2020-12-23 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018553846A Expired - Fee Related JP6803923B2 (ja) | 2015-12-30 | 2016-12-29 | 金属酵素阻害化合物 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US10464922B2 (enExample) |
| EP (1) | EP3397629B1 (enExample) |
| JP (1) | JP6803923B2 (enExample) |
| KR (1) | KR102240920B1 (enExample) |
| CN (1) | CN108779094B (enExample) |
| AU (1) | AU2016380349B2 (enExample) |
| BR (1) | BR112018013522A2 (enExample) |
| CA (1) | CA3006469C (enExample) |
| EA (1) | EA038421B1 (enExample) |
| MX (1) | MX376201B (enExample) |
| TW (1) | TWI623528B (enExample) |
| WO (1) | WO2017117393A1 (enExample) |
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| MX382905B (es) | 2014-03-19 | 2025-03-13 | Viamet Pharmaceuticals Nc Inc | 2-(2,4-difluorofenil)-1,1-difluoro-1-(5-sustituido-piridin-2-il)-3-(1h-tetrazol-1-il)propan-2-oles y procesos para su preparacion. |
| JP2017514790A (ja) | 2014-03-19 | 2017-06-08 | ヴィアメット ファーマスーティカルズ，インコーポレイテッド | 抗真菌化合物の調製方法 |
| JP6606508B2 (ja) | 2014-03-19 | 2019-11-13 | マイコヴィア ファーマシューティカルズ，インコーポレイテッド | 抗真菌化合物の調製方法 |
| MX371291B (es) | 2014-03-19 | 2020-01-24 | Viamet Pharmaceuticals Nc Inc | 2-(2,4-difluorofenil)-1,1-difluoro-1-(5-sustituido-piridin-2-il)- 3-(1h-tetrazol-1-il)propan-2-oles y procedimientos para su preparacion. |
| AU2015231220B2 (en) | 2014-03-19 | 2019-04-04 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Antifungal compound process |
| JP6572234B2 (ja) | 2014-03-19 | 2019-09-04 | ヴィアメット ファーマスーティカルズ（エヌシー），インコーポレイテッド | 抗真菌化合物の調製方法 |
| AU2015231234B2 (en) | 2014-03-19 | 2019-04-04 | Mycovia Pharmaceuticals, Inc. | Antifungal compound process |
| EA037587B1 (ru) | 2014-03-19 | 2021-04-19 | Майковиа Фармасьютикалс, Инк. | Способ получения противогрибковых соединений |
| JP6518683B2 (ja) | 2014-03-19 | 2019-05-22 | ヴィアメット ファーマスーティカルズ（エヌシー），インコーポレイテッド | 抗真菌化合物の調製方法 |
| MX391538B (es) | 2015-09-18 | 2025-03-21 | Mycovia Pharmaceuticals Inc | Proceso de compuesto antifungico. |
| WO2019182743A1 (en) * | 2018-03-20 | 2019-09-26 | Innocrin Pharmaceuticals, Inc. | Compositions for the treatment of brain tumors |
| US12357615B2 (en) | 2018-10-11 | 2025-07-15 | Kembi Therapeutics Pty Ltd | Compositions for the treatment of brain tumors |
| WO2022216680A1 (en) | 2021-04-05 | 2022-10-13 | Halia Therapeutics, Inc. | Nek7 inhibitors |
| CN113444131B (zh) * | 2021-06-24 | 2022-10-21 | 鲁东大学 | N-乙酰氨基葡萄糖类化合物及其制备方法和应用 |
| WO2023069613A1 (en) * | 2021-10-20 | 2023-04-27 | Ohio State Innovation Foundation | Arylimidamides for use in treatment of cancers |
| CN115466227B (zh) * | 2022-06-30 | 2024-07-19 | 杭州国瑞生物科技有限公司 | 一种3-(氯甲基)-1-甲基-1h-1,2,4-三唑盐酸盐的制备方法 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5087240A (en) | 1983-08-18 | 1992-02-11 | Drug Delivery Systems Inc. | Transdermal drug patch with conductive fibers |
| US4921475A (en) | 1983-08-18 | 1990-05-01 | Drug Delivery Systems Inc. | Transdermal drug patch with microtubes |
| US4738851A (en) | 1985-09-27 | 1988-04-19 | University Of Iowa Research Foundation, Inc. | Controlled release ophthalmic gel formulation |
| US5163899A (en) | 1987-03-20 | 1992-11-17 | Drug Delivery Systems Inc. | Transdermal drug delivery system |
| US5312325A (en) | 1987-05-28 | 1994-05-17 | Drug Delivery Systems Inc | Pulsating transdermal drug delivery system |
| GB8804164D0 (en) | 1988-02-23 | 1988-03-23 | Tucker J M | Bandage for administering physiologically active compound |
| US4882150A (en) | 1988-06-03 | 1989-11-21 | Kaufman Herbert E | Drug delivery system |
| US5008110A (en) | 1988-11-10 | 1991-04-16 | The Procter & Gamble Company | Storage-stable transdermal patch |
| US5088977A (en) | 1988-12-21 | 1992-02-18 | Drug Delivery Systems Inc. | Electrical transdermal drug applicator with counteractor and method of drug delivery |
| US5521222A (en) | 1989-09-28 | 1996-05-28 | Alcon Laboratories, Inc. | Topical ophthalmic pharmaceutical vehicles |
| ATE107176T1 (de) | 1989-12-04 | 1994-07-15 | Searle & Co | System zur transdermalen albuterol applikation. |
| US5077033A (en) | 1990-08-07 | 1991-12-31 | Mediventures Inc. | Ophthalmic drug delivery with thermo-irreversible gels of polxoxyalkylene polymer and ionic polysaccharide |
| EP0495421B1 (en) | 1991-01-15 | 1996-08-21 | Alcon Laboratories, Inc. | Use of carrageenans in topical ophthalmic compositions |
| US5352456A (en) | 1991-10-10 | 1994-10-04 | Cygnus Therapeutic Systems | Device for administering drug transdermally which provides an initial pulse of drug |
| JPH07502219A (ja) | 1991-12-18 | 1995-03-09 | ミネソタ マイニング アンド マニュファクチャリング カンパニー | 多重層型バリアー構造体 |
| ATE132381T1 (de) | 1992-01-29 | 1996-01-15 | Voelkl Franz Ski | Ballspielschläger, insbesondere tennisschläger |
| ATE360617T1 (de) * | 1994-06-15 | 2007-05-15 | Otsuka Pharma Co Ltd | Benzoheterocyclische verbindungen verwendbar als vasopressin- oder oxytocin-modulatoren |
| IL114193A (en) | 1994-06-20 | 2000-02-29 | Teva Pharma | Ophthalmic pharmaceutical compositions based on sodium alginate |
| ES2094688B1 (es) | 1994-08-08 | 1997-08-01 | Cusi Lab | Manoemulsion del tipo de aceite en agua, util como vehiculo oftalmico y procedimiento para su preparacion. |
| IT1283911B1 (it) | 1996-02-05 | 1998-05-07 | Farmigea Spa | Soluzioni oftalmiche viscosizzate con polisaccaridi della gomma di tamarindo |
| US5800807A (en) | 1997-01-29 | 1998-09-01 | Bausch & Lomb Incorporated | Ophthalmic compositions including glycerin and propylene glycol |
| US6261547B1 (en) | 1998-04-07 | 2001-07-17 | Alcon Manufacturing, Ltd. | Gelling ophthalmic compositions containing xanthan gum |
| US6197934B1 (en) | 1998-05-22 | 2001-03-06 | Collagenesis, Inc. | Compound delivery using rapidly dissolving collagen film |
| AUPP999799A0 (en) * | 1999-04-27 | 1999-05-20 | Fujisawa Pharmaceutical Co., Ltd. | New compound |
| EP2090165A3 (en) * | 2001-04-03 | 2012-03-28 | Schering Corporation | Antifungal composition with enhanced bioavailability |
| JP5266430B2 (ja) * | 2010-04-24 | 2013-08-21 | ヴィアメット ファーマスーティカルズ，インコーポレイテッド | 金属酵素阻害化合物 |
| US9029389B2 (en) * | 2011-04-21 | 2015-05-12 | Institut Pasteur Korea | Anti-inflammation compounds |
| EA201491386A1 (ru) * | 2012-01-20 | 2014-11-28 | Вайамет Фармасьютикалс, Инк. | Соединения, ингибирующие металлоферменты |
| AU2013209516A1 (en) * | 2012-01-20 | 2014-08-28 | Viamet Pharmaceuticals (NC), Inc. | Metalloenzyme inhibitor compounds |
| EA201690007A1 (ru) * | 2013-06-12 | 2016-04-29 | Ваймет Фармасьютикалс, Инк. | Соединения, ингибирующие металлоферменты |
| AU2015231270B2 (en) * | 2014-03-19 | 2019-03-07 | Viamet Pharmaceuticals (NC), Inc. | Antifungal compound process |
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- 2016-12-29 JP JP2018553846A patent/JP6803923B2/ja not_active Expired - Fee Related
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| BR112018013522A2 (pt) | 2018-12-11 |
| CA3006469C (en) | 2023-01-10 |
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| CN108779094A (zh) | 2018-11-09 |
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| AU2016380349B2 (en) | 2020-10-29 |
| EA201891539A1 (ru) | 2018-12-28 |
| KR20180099845A (ko) | 2018-09-05 |
| WO2017117393A1 (en) | 2017-07-06 |
| US10464922B2 (en) | 2019-11-05 |
| EP3397629B1 (en) | 2023-04-19 |
| CA3006469A1 (en) | 2017-07-06 |
| TW201734000A (zh) | 2017-10-01 |
| EA038421B1 (ru) | 2021-08-26 |
| MX376201B (es) | 2025-03-07 |
| CN108779094B (zh) | 2021-11-16 |
| TWI623528B (zh) | 2018-05-11 |
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