KR102765806B1 - 바소프레신 수용체 길항제 및 그와 관련된 제품 및 방법 - Google Patents
바소프레신 수용체 길항제 및 그와 관련된 제품 및 방법 Download PDFInfo
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- KR102765806B1 KR102765806B1 KR1020207009443A KR20207009443A KR102765806B1 KR 102765806 B1 KR102765806 B1 KR 102765806B1 KR 1020207009443 A KR1020207009443 A KR 1020207009443A KR 20207009443 A KR20207009443 A KR 20207009443A KR 102765806 B1 KR102765806 B1 KR 102765806B1
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Classifications
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- 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
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- 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
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/554—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762554452P | 2017-09-05 | 2017-09-05 | |
| US62/554,452 | 2017-09-05 | ||
| PCT/US2018/049607 WO2019050988A1 (en) | 2017-09-05 | 2018-09-05 | ANTAGONISTS OF THE VASOPRESSIN RECEPTOR, PRODUCTS AND RELATED METHODS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20200051686A KR20200051686A (ko) | 2020-05-13 |
| KR102765806B1 true KR102765806B1 (ko) | 2025-02-10 |
Family
ID=63708454
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020207009443A Active KR102765806B1 (ko) | 2017-09-05 | 2018-09-05 | 바소프레신 수용체 길항제 및 그와 관련된 제품 및 방법 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US10538530B2 (enExample) |
| EP (1) | EP3679043B9 (enExample) |
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| CN106810536A (zh) | 2015-11-30 | 2017-06-09 | 甘李药业股份有限公司 | 一种蛋白激酶抑制剂及其制备方法和医药用途 |
| PE20231372A1 (es) | 2020-09-03 | 2023-09-07 | Hoffmann La Roche | Compuestos heterociclicos |
| AU2022260537A1 (en) * | 2021-04-23 | 2023-09-21 | F. Hoffmann-La Roche Ag | Heterocyclic compounds |
| IL313987A (en) | 2021-12-29 | 2024-08-01 | Psy Therapeutics Inc | Inhibiting monoacylglycerol lipase (magl) |
| US20250170100A1 (en) * | 2021-12-29 | 2025-05-29 | Psy Therapeutics, Inc. | Monoacylglycerol lipase inhibitors and use thereof for the treatment of anxiety and related conditions |
| WO2023130050A1 (en) * | 2021-12-29 | 2023-07-06 | Psy Therapeutics, Inc. | Monoacylglycerol lipase inhibitors and use thereof for the treatment and management of pain |
| AU2023323878A1 (en) * | 2022-08-11 | 2025-01-30 | Remynd N.V. | (aza)spiroheptane derivatives for the treatment of neurodegenerative disorders |
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Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2025005A (en) * | 1930-01-02 | 1935-12-17 | Union Switch & Signal Co | Multiple control apparatus |
| DE3930262A1 (de) * | 1989-09-11 | 1991-03-21 | Thomae Gmbh Dr K | Kondensierte diazepinone, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US5091387A (en) * | 1990-03-02 | 1992-02-25 | Merck & Co., Inc. | Spirocyclic oxytocin antagonists |
| JP2003505388A (ja) * | 1999-07-21 | 2003-02-12 | アストラゼネカ・アクチエボラーグ | 新規化合物 |
| CA2581150A1 (en) * | 2004-09-17 | 2006-03-30 | Osi Pharmaceuticals, Inc. | (spirocyclylamido) aminothiophene compounds as c-kit proto- oncogene inhibitors |
| PL1912976T3 (pl) * | 2005-07-21 | 2009-04-30 | Hoffmann La Roche | Pochodne indol-3-ilokarbonylopiperydynobenzoimidazolu jako antagoniści receptora V1a |
| US7351706B2 (en) * | 2006-01-05 | 2008-04-01 | Hoffmann-La Roche Inc. | Indol-3-yl-carbonyl-spiro-piperidine derivatives |
| EP2076517A1 (en) * | 2006-09-22 | 2009-07-08 | Janssen Pharmaceutica N.V. | Spiro benzazepines as vasopressin antagonists |
| JP2010511654A (ja) * | 2006-12-07 | 2010-04-15 | エフ．ホフマン−ラ ロシュ アーゲー | スピロ−ピペリジン誘導体 |
| CN101547923A (zh) * | 2006-12-07 | 2009-09-30 | 弗·哈夫曼-拉罗切有限公司 | 作为via受体拮抗剂的螺环-哌啶衍生物 |
| US8329904B2 (en) | 2009-05-12 | 2012-12-11 | Hoffmann-La Roche Inc. | Azacyclic derivatives |
| KR20120099415A (ko) * | 2009-09-24 | 2012-09-10 | 샤이어-모베티스 엔.브이. | 바소프레신 ｖ２ 리셉터 길항제로서의 (１，４)-벤조디아제핀 |
| US20150376198A1 (en) | 2013-02-18 | 2015-12-31 | The Scripps Research Institute | Modulators of vasopressin receptors with therapeutic potential |
| CN105992587A (zh) | 2013-02-18 | 2016-10-05 | 春堤制药公司 | 作为疫苗佐剂和治疗试剂的短寡核苷酸的设计 |
| US9688678B2 (en) * | 2014-05-15 | 2017-06-27 | AbbVie Deutschland GmbH & Co. KG | Oxindole compounds carrying a nitrogen-bound spiro substituent and use thereof for treating vasopressin-related diseases |
| US11186577B2 (en) * | 2017-06-05 | 2021-11-30 | Blackthorn Therapeutics, Inc. | Vasopressin receptor antagonists and products and methods related thereto |
| EP3894414B1 (en) | 2018-12-12 | 2024-04-10 | Neumora Therapeutics, Inc. | 1-(2,6-diazaspiro[3.3]heptan-6-yl)-5,6-dihydro-4h-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine derivatives as vasopressin antagonists for the treatment of neuro-psychological disorders |
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