ES2367369T3 - Inhibidores de enzimas. - Google Patents
Inhibidores de enzimas. Download PDFInfo
- Publication number
- ES2367369T3 ES2367369T3 ES06726982T ES06726982T ES2367369T3 ES 2367369 T3 ES2367369 T3 ES 2367369T3 ES 06726982 T ES06726982 T ES 06726982T ES 06726982 T ES06726982 T ES 06726982T ES 2367369 T3 ES2367369 T3 ES 2367369T3
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- Spain
- Prior art keywords
- compound
- optionally substituted
- radical
- alkyl
- mmol
- 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.)
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Classifications
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/40—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
- C07C275/20—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
- C07C275/24—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
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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
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/45—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the singly-bound nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfonamides
- C07C311/46—Y being a hydrogen or a carbon atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
- C07C317/48—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C317/50—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/36—Oxygen or sulfur atoms
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
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| ES2402252B1 (es) * | 2011-09-26 | 2014-03-10 | Universidad De Granada | Compuesto con actividad antileishmania |
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| AR103598A1 (es) | 2015-02-02 | 2017-05-24 | Forma Therapeutics Inc | Ácidos bicíclicos[4,6,0]hidroxámicos como inhibidores de hdac |
| ES2899002T3 (es) * | 2016-03-22 | 2022-03-09 | Inst Nat Sante Rech Med | Nuevos derivados y su uso como inhibidores selectivos de Caspasa-2 |
| WO2017216297A1 (en) | 2016-06-16 | 2017-12-21 | Glaxosmithkline Intellectual Property Development Limited | Dosage regimen |
| EP3472131B1 (en) | 2016-06-17 | 2020-02-19 | Forma Therapeutics, Inc. | 2-spiro-5- and 6-hydroxamic acid indanes as hdac inhibitors |
| GB201713975D0 (en) | 2017-08-31 | 2017-10-18 | Macrophage Pharma Ltd | Medical use |
| TWI650139B (zh) * | 2017-10-11 | 2019-02-11 | 行政院原子能委員會核能硏究所 | 含有放射性同位素氟的異羥肟酸類造影劑、其製備方法及其用途 |
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Family Cites Families (43)
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|---|---|---|---|---|
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| BR0014254A (pt) | 1999-09-08 | 2002-08-27 | Sloan Kettering Inst Cancer | Nova classe de agentes de citodiferenciação e inibidores de desacetilase de histona, e métodos de uso dos mesmos |
| KR20070053362A (ko) | 1999-11-23 | 2007-05-23 | 메틸진, 인크. | 히스톤 디아세틸라제의 억제제 |
| GB0003476D0 (en) | 2000-02-16 | 2000-04-05 | British Biotech Pharm | Acetal Hydroxylamine compounds |
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| US6784173B2 (en) | 2001-06-15 | 2004-08-31 | Hoffmann-La Roche Inc. | Aromatic dicarboxylic acid derivatives |
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| NZ534771A (en) | 2002-03-13 | 2006-04-28 | Janssen Pharmaceutica Nv | Sulfonylamino-derivatives as novel inhibitors of histone deacetylase |
| ES2347544T3 (es) | 2002-03-13 | 2010-11-02 | Janssen Pharmaceutica Nv | Inhibidores de histona-desacetilasas. |
| OA12792A (en) | 2002-03-13 | 2006-07-10 | Janssen Pharmaceutica Nv | Sulfonyl-derivatives as novel inhibitors of histone deacetylase. |
| ES2306858T3 (es) | 2002-03-13 | 2008-11-16 | Janssen Pharmaceutica Nv | Derivados de carbonilamino como nuevos inhibidores de las histonadesacetilasas. |
| EP1492534B1 (en) | 2002-04-03 | 2008-06-25 | TopoTarget UK Limited | Carbamic acid compounds comprising a piperazine linkage as hdac inhibitors |
| TWI319387B (en) | 2002-04-05 | 2010-01-11 | Astrazeneca Ab | Benzamide derivatives |
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| WO2004092115A2 (en) | 2003-04-07 | 2004-10-28 | Axys Pharmaceuticals Inc. | Hydroxamates as therapeutic agents |
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| EP1644323B1 (en) | 2003-07-07 | 2015-03-18 | Georgetown University | Histone deacetylase inhibitors and methods of use thereof |
| US7723376B2 (en) | 2003-07-15 | 2010-05-25 | Korea Research Institute Of Bioscience And Biotechnology | 2-oxo-heterocyclic compounds and pharmaceutical compositions |
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| JP2008540389A (ja) | 2008-11-20 |
| CN101133060B (zh) | 2013-06-05 |
| EP2301939A1 (en) | 2011-03-30 |
| GB0509223D0 (en) | 2005-06-15 |
| US20130116318A1 (en) | 2013-05-09 |
| MX2007010456A (es) | 2007-10-11 |
| US7939666B2 (en) | 2011-05-10 |
| KR20080015388A (ko) | 2008-02-19 |
| KR101307815B1 (ko) | 2013-09-12 |
| BRPI0607410A2 (pt) | 2009-09-01 |
| US20090291978A1 (en) | 2009-11-26 |
| IL185580A0 (en) | 2008-01-06 |
| AU2006243065B2 (en) | 2012-05-03 |
| EP1879895B1 (en) | 2011-06-08 |
| EP1879895A1 (en) | 2008-01-23 |
| DK1879895T3 (da) | 2011-09-19 |
| NZ560289A (en) | 2010-11-26 |
| IL185580A (en) | 2012-08-30 |
| CN101133060A (zh) | 2008-02-27 |
| US20140163042A1 (en) | 2014-06-12 |
| JP5405820B2 (ja) | 2014-02-05 |
| WO2006117549A1 (en) | 2006-11-09 |
| CA2599411C (en) | 2013-12-03 |
| PL1879895T3 (pl) | 2011-11-30 |
| ZA200707091B (en) | 2008-10-29 |
| CA2599411A1 (en) | 2006-11-09 |
| PT1879895E (pt) | 2011-09-06 |
| AU2006243065A1 (en) | 2006-11-09 |
| US9133104B2 (en) | 2015-09-15 |
| US8686032B2 (en) | 2014-04-01 |
| ATE512150T1 (de) | 2011-06-15 |
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