WO2007095584A3 - Histone Deacetylase Inhibitors - Google Patents

Histone Deacetylase Inhibitors Download PDF

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Publication number
WO2007095584A3
WO2007095584A3 PCT/US2007/062152 US2007062152W WO2007095584A3 WO 2007095584 A3 WO2007095584 A3 WO 2007095584A3 US 2007062152 W US2007062152 W US 2007062152W WO 2007095584 A3 WO2007095584 A3 WO 2007095584A3
Authority
WO
WIPO (PCT)
Prior art keywords
compounds
particularly useful
histone deacetylase
esterase
deacetylase inhibitors
Prior art date
Application number
PCT/US2007/062152
Other languages
French (fr)
Other versions
WO2007095584A2 (en
Inventor
James Elliot Bradner
Ralph Mazitschek
Original Assignee
Harvard College
Dana Farber Cancer Inst Inc
James Elliot Bradner
Ralph Mazitschek
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to ES07757000.0T priority Critical patent/ES2481413T3/en
Application filed by Harvard College, Dana Farber Cancer Inst Inc, James Elliot Bradner, Ralph Mazitschek filed Critical Harvard College
Priority to MX2008010462A priority patent/MX2008010462A/en
Priority to AU2007214458A priority patent/AU2007214458C1/en
Priority to JP2008555472A priority patent/JP5409015B2/en
Priority to BRPI0707826-9A priority patent/BRPI0707826B1/en
Priority to US12/279,398 priority patent/US8383855B2/en
Priority to DK07757000.0T priority patent/DK2010168T3/en
Priority to CA2642288A priority patent/CA2642288C/en
Priority to EP07757000.0A priority patent/EP2010168B1/en
Priority to PL07757000T priority patent/PL2010168T3/en
Publication of WO2007095584A2 publication Critical patent/WO2007095584A2/en
Priority to IL193458A priority patent/IL193458A/en
Publication of WO2007095584A3 publication Critical patent/WO2007095584A3/en
Priority to HK09105914.3A priority patent/HK1126754A1/en
Priority to US13/944,320 priority patent/US20140213620A1/en
Priority to US14/198,764 priority patent/US9199923B2/en
Priority to US14/862,679 priority patent/US9724321B2/en
Priority to US15/637,078 priority patent/US10172821B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/231—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
    • C07C235/76—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
    • C07C235/78—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton the carbon skeleton containing rings
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for exmaple. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.
PCT/US2007/062152 2006-02-14 2007-02-14 Histone Deacetylase Inhibitors WO2007095584A2 (en)

Priority Applications (16)

Application Number Priority Date Filing Date Title
CA2642288A CA2642288C (en) 2006-02-14 2007-02-14 Histone deacetylase inhibitors
DK07757000.0T DK2010168T3 (en) 2006-02-14 2007-02-14 Histone deacetylase inhibitore
MX2008010462A MX2008010462A (en) 2006-02-14 2007-02-14 Histone Deacetylase Inhibitors.
AU2007214458A AU2007214458C1 (en) 2006-02-14 2007-02-14 Histone deacetylase inhibitors
JP2008555472A JP5409015B2 (en) 2006-02-14 2007-02-14 Histone deacetylase inhibitor
BRPI0707826-9A BRPI0707826B1 (en) 2006-02-14 2007-02-14 Histone deacetylase inhibitor compounds, pharmaceutical composition and use of said compounds
US12/279,398 US8383855B2 (en) 2006-02-14 2007-02-14 Histone deacetylase inhibitors
ES07757000.0T ES2481413T3 (en) 2006-02-14 2007-02-14 Histone Deacetylase Inhibitors
PL07757000T PL2010168T3 (en) 2006-02-14 2007-02-14 Histone deacetylase inhibitors
EP07757000.0A EP2010168B1 (en) 2006-02-14 2007-02-14 Histone deacetylase inhibitors
IL193458A IL193458A (en) 2006-02-14 2008-08-14 Histone deacetylase inhibitors
HK09105914.3A HK1126754A1 (en) 2006-02-14 2009-07-02 Histone deacetylase inhibitors
US13/944,320 US20140213620A1 (en) 2006-02-14 2013-07-17 Histone deacetylase inhibitors
US14/198,764 US9199923B2 (en) 2006-02-14 2014-03-06 Histone deacetylase inhibitors
US14/862,679 US9724321B2 (en) 2006-02-14 2015-09-23 Histone deacetylase inhibitors
US15/637,078 US10172821B2 (en) 2006-02-14 2017-06-29 Histone deacetylase inhibitors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US77317206P 2006-02-14 2006-02-14
US60/773,172 2006-02-14

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12/279,398 A-371-Of-International US8383855B2 (en) 2006-02-14 2007-02-14 Histone deacetylase inhibitors
US201213678983A Continuation 2006-02-14 2012-11-16

Publications (2)

Publication Number Publication Date
WO2007095584A2 WO2007095584A2 (en) 2007-08-23
WO2007095584A3 true WO2007095584A3 (en) 2009-05-22

Family

ID=38372243

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2007/062152 WO2007095584A2 (en) 2006-02-14 2007-02-14 Histone Deacetylase Inhibitors

Country Status (14)

Country Link
US (5) US8383855B2 (en)
EP (1) EP2010168B1 (en)
JP (2) JP5409015B2 (en)
CN (2) CN101528679A (en)
AU (1) AU2007214458C1 (en)
BR (1) BRPI0707826B1 (en)
CA (1) CA2642288C (en)
DK (1) DK2010168T3 (en)
ES (1) ES2481413T3 (en)
HK (1) HK1126754A1 (en)
IL (1) IL193458A (en)
MX (1) MX2008010462A (en)
PL (1) PL2010168T3 (en)
WO (1) WO2007095584A2 (en)

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EP1991247B1 (en) 2006-02-14 2015-10-14 President and Fellows of Harvard College Bifunctional histone deacetylase inhibitors
DK2010168T3 (en) 2006-02-14 2014-07-21 Harvard College Histone deacetylase inhibitore
EP2019674B1 (en) * 2006-05-03 2016-11-23 The President and Fellows of Harvard College Histone deacetylase and tubulin deacetylase inhibitors
EP2321264B1 (en) 2008-07-23 2016-05-04 President and Fellows of Harvard College Deacetylase inhibitors and uses thereof
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CN103347498B (en) 2010-10-13 2016-04-13 沙普药品公司 Histone deacetylase inhibitor pharmaceutical formulation
CN104447608B (en) * 2014-11-10 2017-01-11 华东师范大学 Hydroxamic acid micromolecule organic compound with thaizolidinone structure as well as derivatives, application and preparation method of hydroxamic acid micromolecule organic compounds
CN104744431A (en) * 2015-03-06 2015-07-01 芜湖杨燕制药有限公司 Histone deacetylase inhibitor as well as preparation method and application thereof
US20230190717A1 (en) * 2017-04-10 2023-06-22 City Of Hope P38 gamma inhibitors and method of use thereof
CN108299313B (en) * 2018-01-16 2020-10-02 长沙霍滋生物科技有限公司 Compound and application thereof in pharmacy
CN111943892B (en) * 2019-05-17 2022-04-05 上海中泽医药科技有限公司 Histone deacetylase subtype inhibitor thioacetylarylamine compound and application thereof
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