JP7157804B2 - Ｎｌｒｐ活性に関連する病態を治療するためのスルホンアミド及びその組成物 - Google Patents
Ｎｌｒｐ活性に関連する病態を治療するためのスルホンアミド及びその組成物 Download PDFInfo
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- JP7157804B2 JP7157804B2 JP2020521522A JP2020521522A JP7157804B2 JP 7157804 B2 JP7157804 B2 JP 7157804B2 JP 2020521522 A JP2020521522 A JP 2020521522A JP 2020521522 A JP2020521522 A JP 2020521522A JP 7157804 B2 JP7157804 B2 JP 7157804B2
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- membered heterocycloalkyl
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D209/04—Indoles; Hydrogenated indoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
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- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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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- Thiazole And Isothizaole Compounds (AREA)
- Furan Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Quinoline Compounds (AREA)
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| JP2020537657A JP2020537657A (ja) | 2020-12-24 |
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Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MA49903A (fr) | 2017-08-15 | 2020-06-24 | Inflazome Ltd | Sulfonylureés et sulfonylthioureés en tant qu'inhibiteurs de nlrp3 |
| EP3759090A1 (en) | 2018-03-02 | 2021-01-06 | Inflazome Limited | Novel compounds |
| EP3759078A1 (en) | 2018-03-02 | 2021-01-06 | Inflazome Limited | Novel compounds |
| WO2019166627A1 (en) | 2018-03-02 | 2019-09-06 | Inflazome Limited | Novel compounds |
| US11530200B2 (en) | 2018-03-02 | 2022-12-20 | Inflazome Limited | Compounds |
| JP2021529186A (ja) * | 2018-07-03 | 2021-10-28 | ノバルティス アーゲー | Ｎｌｒｐ調節剤 |
| GB201902327D0 (en) | 2019-02-20 | 2019-04-03 | Inflazome Ltd | Novel compounds |
| KR20210053910A (ko) | 2018-08-15 | 2021-05-12 | 인플라좀 리미티드 | 신규한 설폰아마이드유레아 화합물 |
| GB201819083D0 (en) | 2018-11-23 | 2019-01-09 | Inflazome Ltd | Novel compounds |
| GB201905265D0 (en) | 2019-04-12 | 2019-05-29 | Inflazome Ltd | Inflammasome inhibition |
| EP3986879B1 (en) | 2019-06-21 | 2024-10-02 | AC Immune SA | Fused 1,2-thiazoles and 1,2-thiazines which act as nlrp3 modulators |
| KR20220064364A (ko) | 2019-07-17 | 2022-05-18 | 조마젠 바이오사이언시즈 엘티디 | 다발성 경화증(ms)의 치료를 위한 nlpr3 조절제로서의 n-((1,2,3,5,6,7-헥사하이드로-s-인다센-4-일)카바모일)-4,5,6,7-테트라하이드로벤조푸란-2-설폰아미드 유도체 및 관련 화합물 |
| EP3999179A1 (en) | 2019-07-17 | 2022-05-25 | Zomagen Biosciences Ltd | Nlrp3 modulators |
| WO2021032588A1 (en) | 2019-08-16 | 2021-02-25 | Inflazome Limited | Macrocyclic sulfonylamide derivatives useful as nlrp3 inhibitors |
| US20220289692A1 (en) | 2019-09-06 | 2022-09-15 | Inflazome Limited | Nlrp3 inhibitors |
| CN114641287A (zh) * | 2019-11-07 | 2022-06-17 | 英夫拉索姆有限公司 | 神经退行性病症的治疗和预防 |
| JP7392169B2 (ja) * | 2019-11-12 | 2023-12-05 | 成都百裕制薬股▲ふん▼有限公司 | アミド誘導体及びその調製方法並びに医薬における応用 |
| PH12022552447A1 (en) | 2020-03-16 | 2024-01-03 | Zomagen Biosciences Ltd | Nlrp3 modulators |
| AU2021257619A1 (en) | 2020-04-15 | 2022-12-15 | Janssen Pharmaceutica Nv | Pyrazolo[1,5-d][1,2,4]triazine-5(4H)-acetamides as inhibitors of the NLRP3 inflammasome pathway |
| CN115485026A (zh) | 2020-04-15 | 2022-12-16 | 詹森药业有限公司 | Nlrp3炎体途径抑制剂吡唑并[1，2-d][1，2，4]三嗪-2-基-乙酰胺 |
| EP4139312A1 (en) | 2020-04-23 | 2023-03-01 | JANSSEN Pharmaceutica NV | Tricyclic compounds as inhibitors of nlrp3 |
| MX2022013637A (es) | 2020-04-30 | 2022-11-16 | Janssen Pharmaceutica Nv | Nuevos compuestos de triazinoindol. |
| US20230202989A1 (en) | 2020-05-28 | 2023-06-29 | Janssen Pharmaceutica Nv | Compounds |
| AU2021291065B2 (en) | 2020-06-19 | 2025-06-26 | Ac Immune Sa | Dihydrooxazole and thiourea or urea derivatives modulating the nlrp3 inflammasome pathway |
| US12577211B2 (en) | 2020-06-29 | 2026-03-17 | Bacainn Biotherapeutics, Ltd. | Probenecid compounds for the treatment of inflammasome-mediated lung disease |
| WO2022023907A1 (en) | 2020-07-31 | 2022-02-03 | Novartis Ag | Methods of selecting and treating patients at elevated risk of major adverse cardiac events |
| EP3974415A1 (en) | 2020-09-24 | 2022-03-30 | Janssen Pharmaceutica NV | Nlrp3 modulators |
| CN116194445A (zh) | 2020-09-24 | 2023-05-30 | 詹森药业有限公司 | 新化合物 |
| CN114133345A (zh) * | 2020-12-17 | 2022-03-04 | 顺毅宜昌化工有限公司 | 一种2-氯磺酰基-4-甲磺酰胺甲基苯甲酸甲酯的制备方法 |
| CN116964052A (zh) | 2021-03-04 | 2023-10-27 | 詹森药业有限公司 | 调节nlrp3的4-氨基-6-氧代-哒嗪衍生物 |
| JP2024508017A (ja) | 2021-03-04 | 2024-02-21 | ヤンセン ファーマシューティカ エヌ．ベー． | Ｎｌｒｐ３を調節する４－アルコキシ－６－オキソ－ピリダジン誘導体 |
| US11932630B2 (en) | 2021-04-16 | 2024-03-19 | Novartis Ag | Heteroaryl aminopropanol derivatives |
| CN116917282A (zh) * | 2021-05-10 | 2023-10-20 | 成都百裕制药股份有限公司 | 酰胺衍生物及其应用 |
| KR20240029027A (ko) | 2021-07-01 | 2024-03-05 | 얀센 파마슈티카 엔브이 | 5-옥소-피리도[2,3-d]피리다진-6(5H)-일 아세트아미드 |
| CN115677616B (zh) * | 2021-11-03 | 2024-10-18 | 中国药科大学 | 大环磺酰胺类化合物及其制备方法和医药用途 |
| CN118541366A (zh) | 2021-12-22 | 2024-08-23 | Ac免疫有限公司 | 二氢噁唑衍生物化合物 |
| US20250109154A1 (en) * | 2022-01-27 | 2025-04-03 | The University Of Tokyo | Lysophosphatidylserine analogue, and lysophosphatidylserine analogue-containing phamaceutical composition for treating or preventing fibrosis |
| WO2023158824A1 (en) * | 2022-02-21 | 2023-08-24 | Viva Star Biosciences (Suzhou) Co., Ltd. | Novel bicyclic substituted sulfonylurea compounds as inhibitors of interleukin- 1 activity |
| EP4554945A1 (en) | 2022-07-14 | 2025-05-21 | AC Immune SA | Pyrrolotriazine and imidazotriazine derivatives as modulators of the nlrp3 inflammasome pathway |
| GEAP202516743A (en) | 2022-09-23 | 2025-08-11 | Merck Sharp & Dohme Llc | Phthalazine derivatives useful as inhibitors of nod-like receptor protein 3 |
| AU2024280075A1 (en) | 2023-06-02 | 2025-12-11 | Merck Sharp & Dohme Llc | 5,6-Unsaturated Bicyclic Heterocycles Useful as Inhibitors of Nod-Like Receptor Protein 3 |
| AR134646A1 (es) | 2023-12-14 | 2026-02-04 | Merck Sharp & Dohme Llc | Derivados de indazol útiles como inhibidores de la proteína 3 del receptor similar a nod |
| US20250223290A1 (en) | 2023-12-14 | 2025-07-10 | Merck Sharp & Dohme Llc | Azaindazole derivatives useful as inhibitors of nod-like receptor protein 3 |
| WO2025133307A1 (en) | 2023-12-22 | 2025-06-26 | Ac Immune Sa | Heterocyclic modulators of the nlrp3 inflammasome pathway |
| WO2025153532A1 (en) | 2024-01-16 | 2025-07-24 | NodThera Limited | Nlrp3 inhibitors and glp-1 agonists combination therapies |
| WO2025153624A1 (en) | 2024-01-17 | 2025-07-24 | Ac Immune Sa | Imidazo[1,2-d][1,2,4]triazine derivatives for use as inhibitors of the nlrp3 inflammasome pathway |
| WO2025153625A1 (en) | 2024-01-17 | 2025-07-24 | Ac Immune Sa | Imidazo[1,2-d][1,2,4]triazine derivatives for use as inhibitors of the nlrp3 inflammasome pathway |
| WO2025163069A1 (en) | 2024-01-31 | 2025-08-07 | Ac Immune Sa | Novel compounds |
| WO2026057747A1 (en) | 2024-09-11 | 2026-03-19 | Ac Immune Sa | Therapeutic use of nlrp3 inflammasome pathway inhibitor compounds |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000511200A (ja) | 1997-01-29 | 2000-08-29 | ファイザー・インク | スルホニルウレア誘導体、およびインターロイキン−１の活性を制御する上でのスルホニルウレア誘導体の使用 |
| WO2001023349A1 (fr) | 1999-09-30 | 2001-04-05 | Mitsubishi Chemical Corporation | Derives d'acylsulfonamide |
| WO2003016254A1 (en) | 2001-08-09 | 2003-02-27 | Ono Pharmaceutical Co., Ltd. | Carboxylic acid derivative compounds and drugs comprising these compounds as the active ingredient |
| WO2017129897A1 (fr) | 2016-01-25 | 2017-08-03 | Galderma Research & Development | Inhibiteurs nlrp3 pour le traitement des pathologies cutanées inflammatoires |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4200954A1 (de) * | 1991-04-26 | 1992-10-29 | Bayer Ag | Heterocyclisch substituierte phenylessigsaeurederivate |
| GB9828442D0 (en) * | 1998-12-24 | 1999-02-17 | Karobio Ab | Novel thyroid receptor ligands and method II |
| GB0324269D0 (en) * | 2003-10-16 | 2003-11-19 | Pharmagene Lab Ltd | EP4 receptor antagonists |
| GB0725214D0 (en) * | 2007-12-24 | 2008-02-06 | Karobio Ab | Pharmaceutical compounds |
| CN103172547B (zh) | 2011-12-20 | 2016-10-12 | 天津市国际生物医药联合研究院 | 磺酰胺衍生物的制备及其应用 |
| CN103159674A (zh) | 2013-04-03 | 2013-06-19 | 苏州安诺生物医药技术有限公司 | 2-苯烷酰胺类化合物及其制备方法、药物组合物和用途 |
| US11447460B2 (en) * | 2016-04-18 | 2022-09-20 | Novartis Ag | Compounds and compositions for treating conditions associated with NLRP activity |
-
2018
- 2018-10-12 WO PCT/US2018/055576 patent/WO2019079119A1/en not_active Ceased
- 2018-10-12 CN CN201880077068.6A patent/CN111417622A/zh active Pending
- 2018-10-12 ES ES18796291T patent/ES2927851T3/es active Active
- 2018-10-12 JP JP2020521522A patent/JP7157804B2/ja active Active
- 2018-10-12 US US16/756,358 patent/US11718631B2/en active Active
- 2018-10-12 EP EP18796291.5A patent/EP3697758B1/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000511200A (ja) | 1997-01-29 | 2000-08-29 | ファイザー・インク | スルホニルウレア誘導体、およびインターロイキン−１の活性を制御する上でのスルホニルウレア誘導体の使用 |
| WO2001023349A1 (fr) | 1999-09-30 | 2001-04-05 | Mitsubishi Chemical Corporation | Derives d'acylsulfonamide |
| WO2003016254A1 (en) | 2001-08-09 | 2003-02-27 | Ono Pharmaceutical Co., Ltd. | Carboxylic acid derivative compounds and drugs comprising these compounds as the active ingredient |
| WO2017129897A1 (fr) | 2016-01-25 | 2017-08-03 | Galderma Research & Development | Inhibiteurs nlrp3 pour le traitement des pathologies cutanées inflammatoires |
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| US11718631B2 (en) | 2023-08-08 |
| ES2927851T3 (es) | 2022-11-11 |
| US20220340591A1 (en) | 2022-10-27 |
| CN111417622A (zh) | 2020-07-14 |
| JP2020537657A (ja) | 2020-12-24 |
| EP3697758B1 (en) | 2022-07-06 |
| EP3697758A1 (en) | 2020-08-26 |
| WO2019079119A1 (en) | 2019-04-25 |
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