CN119285591A - 治疗与热休克蛋白通路有关的疾病的具有修饰糖基团的联芳基酰胺类 - Google Patents
治疗与热休克蛋白通路有关的疾病的具有修饰糖基团的联芳基酰胺类 Download PDFInfo
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- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07C233/00—Carboxylic acid amides
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- C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/18—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
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- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
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- C07C235/34—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
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- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/01—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
- C07C59/11—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups containing rings
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- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
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- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
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- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
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- C07D493/04—Ortho-condensed systems
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
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- C07H15/203—Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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- C07H7/04—Carbocyclic radicals
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H9/00—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical
- C07H9/02—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical the hetero ring containing only oxygen as ring hetero atoms
- C07H9/04—Cyclic acetals
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
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Applications Claiming Priority (4)
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| US62/671,047 | 2018-05-14 | ||
| PCT/US2019/032292 WO2019222269A1 (en) | 2018-05-14 | 2019-05-14 | Biaryl amides with modified sugar groups for treatment of diseases associated with heat shock protein pathway |
| CN201980046311.2A CN112513058B (zh) | 2018-05-14 | 2019-05-14 | 治疗与热休克蛋白通路有关的疾病的具有修饰糖基团的联芳基酰胺类 |
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| CN201980046311.2A Active CN112513058B (zh) | 2018-05-14 | 2019-05-14 | 治疗与热休克蛋白通路有关的疾病的具有修饰糖基团的联芳基酰胺类 |
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| SMT201900660T1 (it) | 2012-02-09 | 2020-01-14 | Univ Kansas | Inibitori c-terminali di hsp90 |
| EP3793565B1 (en) | 2018-05-14 | 2022-01-05 | Gilead Sciences, Inc. | Mcl-1 inhibitors |
| JP7508375B2 (ja) | 2018-05-14 | 2024-07-01 | リアタ ファーマシューティカルズ インコーポレイテッド | 熱ショックタンパク質経路に関連する疾患の治療のための、修飾された糖基を有するビアリールアミド |
| TWI778443B (zh) | 2019-11-12 | 2022-09-21 | 美商基利科學股份有限公司 | Mcl1抑制劑 |
| CN114787139B (zh) | 2019-11-26 | 2025-03-11 | 吉利德科学公司 | 用于制备mcl1抑制剂的方法和中间体 |
| EP4247783A1 (en) | 2020-11-19 | 2023-09-27 | Gilead Sciences, Inc. | Processes and intermediates for preparing macrocyclic mcl1 inhibitors |
| WO2023039293A1 (en) * | 2021-09-13 | 2023-03-16 | Rubedo Life Sciences, Inc. | Coumarin derivatives of sugar analogs and uses thereof |
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| DE19512886A1 (de) | 1995-04-06 | 1996-10-10 | Bayer Ag | Substituierte Cycloalkene |
| FR2792320B1 (fr) | 1999-04-19 | 2003-05-09 | Hoechst Marion Roussel Inc | Nouveaux amides aromatiques substitues par un ribose, leur procede de preparation et leur application comme medicaments |
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| CA2456281A1 (en) | 2001-09-21 | 2003-04-03 | Novartis Ag | Pyrane derivatives as both ace- and nep- inhibitors |
| US7208630B2 (en) | 2004-10-27 | 2007-04-24 | University Of Kansas | Heat shock protein 90 inhibitors |
| US8212011B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues |
| WO2006050501A2 (en) | 2004-11-03 | 2006-05-11 | University Of Kansas | Novobiocin analogues as anticancer agents |
| US8212012B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
| US7622451B2 (en) | 2004-11-03 | 2009-11-24 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
| US9120774B2 (en) | 2004-11-03 | 2015-09-01 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
| CA2620566A1 (en) | 2005-08-30 | 2007-03-08 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted benzyl-benzene derivatives, medicaments containing such compounds, their use and process for their manufacture |
| WO2008061108A2 (en) | 2006-11-15 | 2008-05-22 | Forest Laboratories Holdings Limited | Phthalazine derivatives |
| DE102007002715A1 (de) * | 2007-01-18 | 2008-07-24 | Merck Patent Gmbh | Triazolderivat |
| JP5401329B2 (ja) | 2007-03-20 | 2014-01-29 | キュリス，インコーポレイテッド | Ｈｓｐ９０インヒビターとしての縮合アミノピリジン |
| US7960353B2 (en) | 2007-05-10 | 2011-06-14 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
| ES2475206T3 (es) | 2008-02-01 | 2014-07-10 | Takeda Pharmaceutical Company Limited | Derivados de oxima como inhibidores de HSP90 |
| FR2928645A1 (fr) | 2008-03-14 | 2009-09-18 | Sanofi Aventis Sa | Nouveaux derives de carbazole inhibiteurs d'hsp90, compositions les contenant et utilisation |
| US20100022635A1 (en) | 2008-07-28 | 2010-01-28 | University Of Kansas | Heat shock protein 90 inhibitor dosing methods |
| JP5766617B2 (ja) | 2009-02-20 | 2015-08-19 | ユニバーシティ・オブ・カンザス | 修飾された糖部分を有するノボビオシン類似体 |
| US20110082098A1 (en) | 2009-09-30 | 2011-04-07 | University Of Kansas | Novobiocin analogues and treatment of polycystic kidney disease |
| TW201216957A (en) | 2010-07-13 | 2012-05-01 | Dainippon Sumitomo Pharma Co | Biarylamide derivative or a pharmaceutically acceptable salt thereof |
| ES2647889T3 (es) | 2011-04-05 | 2017-12-27 | Sloan-Kettering Institute For Cancer Research | Inhibidores de la Hsp90 |
| US9056104B2 (en) | 2011-05-20 | 2015-06-16 | The University Of Kansas | Dynamic inhibitors of heat shock protein 90 |
| WO2013112548A1 (en) | 2012-01-23 | 2013-08-01 | University Of South Florida | Gamma-aapeptides with potent and broad-spectrum antimicrobial activity |
| SMT201900660T1 (it) | 2012-02-09 | 2020-01-14 | Univ Kansas | Inibitori c-terminali di hsp90 |
| US9422230B2 (en) | 2013-05-09 | 2016-08-23 | Council Of Scientific And Industrial Research | Process for the preparation of an anticonvulsant agent pregabalin hydrochloride |
| AU2014346483B2 (en) | 2013-11-07 | 2019-01-17 | The University Of Kansas | Biphenylamide derivative Hsp90 inhibitors |
| CA2929243C (en) | 2013-11-11 | 2022-05-03 | The University Of Kansas | Coumarin based hsp90 inhibitors with urea and ether substituents |
| CA2951270C (en) | 2014-06-13 | 2023-07-04 | The University Of Kansas | Triazole modified coumarin and biphenyl amide-based hsp90 inhibitors |
| MX388516B (es) * | 2014-06-24 | 2025-03-20 | Univ Kansas | Bifenil amidas con grupos éter modificados como inhibidores de hsp90 e inductores de hsp70. |
| JP7508375B2 (ja) | 2018-05-14 | 2024-07-01 | リアタ ファーマシューティカルズ インコーポレイテッド | 熱ショックタンパク質経路に関連する疾患の治療のための、修飾された糖基を有するビアリールアミド |
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- 2019-05-14 WO PCT/US2019/032292 patent/WO2019222269A1/en not_active Ceased
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| US20210261592A1 (en) | 2021-08-26 |
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| JP7508375B2 (ja) | 2024-07-01 |
| EP3794009A1 (en) | 2021-03-24 |
| UA130486C2 (uk) | 2026-03-04 |
| JP2021524439A (ja) | 2021-09-13 |
| AU2024267017A1 (en) | 2024-12-19 |
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| US20240182507A1 (en) | 2024-06-06 |
| AU2019271126B2 (en) | 2024-08-29 |
| BR112020023277A2 (pt) | 2021-02-23 |
| IL278698B2 (en) | 2024-06-01 |
| IL309891B2 (en) | 2025-03-01 |
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| MX2025007723A (es) | 2025-08-01 |
| PE20211917A1 (es) | 2021-09-28 |
| EA202092727A1 (ru) | 2021-04-20 |
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