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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- A61K31/33—Heterocyclic compounds
- 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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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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
- Health & Medical Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
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- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (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 (https=) |
| EP (1) | EP3679043B9 (https=) |
| JP (1) | JP7368357B2 (https=) |
| KR (1) | KR102765806B1 (https=) |
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Families Citing this family (7)
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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 |
| CA3190277A1 (en) | 2020-09-03 | 2022-03-10 | Joerg Benz | Heterocyclic compounds |
| CN117295726A (zh) * | 2021-04-23 | 2023-12-26 | 豪夫迈·罗氏有限公司 | 杂环化合物 |
| WO2023130050A1 (en) * | 2021-12-29 | 2023-07-06 | Psy Therapeutics, Inc. | Monoacylglycerol lipase inhibitors and use thereof for the treatment and management of pain |
| CA3242372A1 (en) | 2021-12-29 | 2023-07-06 | 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 |
| CN120379996A (zh) * | 2022-08-11 | 2025-07-25 | 瑞敏德股份有限公司 | 用于治疗神经退行性障碍的(氮杂)螺庚烷衍生物 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015173392A1 (en) | 2014-05-15 | 2015-11-19 | AbbVie Deutschland GmbH & Co. KG | Oxindole compounds carrying a co-bound spiro substituent and use thereof for treating vasopressin-related diseases |
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 |
| HUP0203548A3 (en) * | 1999-07-21 | 2003-04-28 | Astrazeneca Ab | New spirooxindole derivatives, process for their preparation, pharmaceutical compositions containing them and their use |
| WO2006034015A1 (en) * | 2004-09-17 | 2006-03-30 | Osi Pharmaceuticals, Inc. | (spirocyclylamido) aminothiophene compounds as c-kit proto- oncogene inhibitors |
| KR100984893B1 (ko) * | 2005-07-21 | 2010-10-01 | 에프. 호프만-라 로슈 아게 | Ｖ1ａ 수용체 길항제로서의인돌-3-일-카보닐-피페리딘-벤조이미다졸 유도체 |
| US7351706B2 (en) * | 2006-01-05 | 2008-04-01 | Hoffmann-La Roche Inc. | Indol-3-yl-carbonyl-spiro-piperidine derivatives |
| JP2010504352A (ja) * | 2006-09-22 | 2010-02-12 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | バソプレッシン拮抗薬としてのスピロベンズアゼピン類 |
| DE602007006990D1 (de) | 2006-12-07 | 2010-07-15 | Hoffmann La Roche | Spiropiperidinderivate als antagonisten des via-rezeptors |
| DE602007006989D1 (en) * | 2006-12-07 | 2010-07-15 | Hoffmann La Roche | Spiropiperidinderivate |
| US8329904B2 (en) | 2009-05-12 | 2012-12-11 | Hoffmann-La Roche Inc. | Azacyclic derivatives |
| WO2011036204A1 (en) * | 2009-09-24 | 2011-03-31 | Shire-Movetis N.V. | [1,4]-benzodiazepines as vasopressin v2 receptor antagonists |
| CN105263910A (zh) | 2013-02-18 | 2016-01-20 | 斯克利普斯研究所 | 具有治疗潜力的血管加压素受体调节剂 |
| JP6502267B2 (ja) | 2013-02-18 | 2019-04-17 | スプリング バンク ファーマシューティカルズ，インコーポレイテッド | ワクチンアジュバントおよび治療剤としての短鎖オリゴヌクレオチドの設計 |
| 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 |
| WO2018226769A1 (en) * | 2017-06-05 | 2018-12-13 | Blackthorn Therapeutics, Inc. | 1-(2-azaspiro[3.3]heptan-6-yl)-5,6-dihydro-4h-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine derivatives as v1a receptor antagonists for treating neuropsychological disorders |
| WO2020123872A1 (en) | 2018-12-12 | 2020-06-18 | Blackthorn 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 and related compounds as vasopressin antagonists for the treatment of neuro-psychological disorders |
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| WO2015173392A1 (en) | 2014-05-15 | 2015-11-19 | AbbVie Deutschland GmbH & Co. KG | Oxindole compounds carrying a co-bound spiro substituent and use thereof for treating vasopressin-related diseases |
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