WO2012010644A1 - Procede de synthese d'isothiocyanates et leurs derives et utilisations de ceux-ci - Google Patents
Procede de synthese d'isothiocyanates et leurs derives et utilisations de ceux-ci Download PDFInfo
- Publication number
- WO2012010644A1 WO2012010644A1 PCT/EP2011/062477 EP2011062477W WO2012010644A1 WO 2012010644 A1 WO2012010644 A1 WO 2012010644A1 EP 2011062477 W EP2011062477 W EP 2011062477W WO 2012010644 A1 WO2012010644 A1 WO 2012010644A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- amine
- group
- process according
- general formula
- sulforaphane
- Prior art date
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- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 57
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 54
- 230000002194 synthesizing Effects 0.000 title claims abstract description 52
- 238000000034 method Methods 0.000 title claims abstract description 49
- 150000002540 isothiocyanates Chemical class 0.000 title description 12
- -1 sulphinyl Chemical group 0.000 claims abstract description 31
- ZBKFYXZXZJPWNQ-UHFFFAOYSA-N [N-]=C=S Chemical compound [N-]=C=S ZBKFYXZXZJPWNQ-UHFFFAOYSA-N 0.000 claims abstract description 30
- 150000001875 compounds Chemical class 0.000 claims abstract description 27
- QGJOPFRUJISHPQ-UHFFFAOYSA-N carbon bisulphide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 230000000875 corresponding Effects 0.000 claims abstract description 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
- 238000005755 formation reaction Methods 0.000 claims abstract description 5
- 125000005418 aryl aryl group Chemical group 0.000 claims abstract description 4
- 150000004763 sulfides Chemical group 0.000 claims abstract 3
- UCKMPCXJQFINFW-UHFFFAOYSA-N sulphide Chemical group [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims abstract 2
- SUVMJBTUFCVSAD-JTQLQIEISA-N 4-Methylsulfinylbutyl isothiocyanate Natural products C[S@](=O)CCCCN=C=S SUVMJBTUFCVSAD-JTQLQIEISA-N 0.000 claims description 141
- 235000015487 sulforaphane Nutrition 0.000 claims description 66
- 150000001412 amines Chemical class 0.000 claims description 50
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- 239000002904 solvent Substances 0.000 claims description 34
- KXJVOLXLYNDZME-UHFFFAOYSA-N 6-isothiocyanatohexan-2-one Chemical compound CC(=O)CCCCN=C=S KXJVOLXLYNDZME-UHFFFAOYSA-N 0.000 claims description 30
- UMGDCJDMYOKAJW-UHFFFAOYSA-N Thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 26
- 238000007792 addition Methods 0.000 claims description 18
- 230000000694 effects Effects 0.000 claims description 18
- 238000007254 oxidation reaction Methods 0.000 claims description 11
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- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 10
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- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000001810 isothiocyanato group Chemical group *N=C=S 0.000 claims description 7
- RHQDFWAXVIIEBN-UHFFFAOYSA-N 2,2,2-trifluoroethyl alcohol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 6
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- PWZUZQNZVZKCBI-UHFFFAOYSA-N O-ethyl carbamothioate Chemical group CCOC(N)=S PWZUZQNZVZKCBI-UHFFFAOYSA-N 0.000 description 1
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- 102000014961 Protein Precursors Human genes 0.000 description 1
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- 235000001014 amino acid Nutrition 0.000 description 1
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- 238000004458 analytical method Methods 0.000 description 1
- RWZYAGGXGHYGMB-UHFFFAOYSA-M anthranilate Chemical compound NC1=CC=CC=C1C([O-])=O RWZYAGGXGHYGMB-UHFFFAOYSA-M 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004429 atoms Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- SIISYXWWQBUDOP-UHFFFAOYSA-N bis(1H-imidazol-2-yl)methanethione Chemical compound N=1C=CNC=1C(=S)C1=NC=CN1 SIISYXWWQBUDOP-UHFFFAOYSA-N 0.000 description 1
- FVSNJSJANRBLMC-UHFFFAOYSA-N bis(2H-triazol-4-yl)methanethione Chemical compound C=1NN=NC=1C(=S)C1=CNN=N1 FVSNJSJANRBLMC-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- GMEGXJPUFRVCPX-UHFFFAOYSA-N butylthiourea Chemical compound CCCCNC(N)=S GMEGXJPUFRVCPX-UHFFFAOYSA-N 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
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- 229920003211 cis-1,4-polyisoprene Polymers 0.000 description 1
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- 238000001816 cooling Methods 0.000 description 1
- 150000001945 cysteines Chemical class 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
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- 238000007872 degassing Methods 0.000 description 1
- 230000035614 depigmentation Effects 0.000 description 1
- 235000019838 diammonium phosphate Nutrition 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000002708 enhancing Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000003834 intracellular Effects 0.000 description 1
- 230000002934 lysing Effects 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000036564 melanin content Effects 0.000 description 1
- AWIJRPNMLHPLNC-UHFFFAOYSA-M methanethioate Chemical compound [O-]C=S AWIJRPNMLHPLNC-UHFFFAOYSA-M 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-M methanethiolate Chemical compound [S-]C LSDPWZHWYPCBBB-UHFFFAOYSA-M 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N n-butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 230000001590 oxidative Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- PVIJLUXKGBJNNI-UHFFFAOYSA-N piperazine-1-carbothioamide Chemical compound NC(=S)N1CCNCC1 PVIJLUXKGBJNNI-UHFFFAOYSA-N 0.000 description 1
- UERQMZVFUXRQOD-UHFFFAOYSA-N piperidine-1-carbothioamide Chemical compound NC(=S)N1CCCCC1 UERQMZVFUXRQOD-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 230000003334 potential Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000001681 protective Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000003507 refrigerant Substances 0.000 description 1
- 230000002441 reversible Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000001577 simple distillation Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- RZWQDAUIUBVCDD-UHFFFAOYSA-M sodium;benzenethiolate Chemical compound [Na+].[S-]C1=CC=CC=C1 RZWQDAUIUBVCDD-UHFFFAOYSA-M 0.000 description 1
- QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical group [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000037072 sun protection Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/16—Isothiocyanates
- C07C331/18—Isothiocyanates having isothiocyanate groups bound to acyclic carbon atoms
- C07C331/22—Isothiocyanates having isothiocyanate groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
- C07C331/24—Isothiocyanates having isothiocyanate groups bound to acyclic carbon atoms of an unsaturated carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
-
- 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
- A61P17/04—Antipruritics
-
- 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
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- 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 anti-inflammatory agents, e.g antirheumatic agents; Non-steroidal anti-inflammatory drugs (NSAIDs)
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious 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
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/16—Isothiocyanates
- C07C331/18—Isothiocyanates having isothiocyanate groups bound to acyclic carbon atoms
- C07C331/20—Isothiocyanates having isothiocyanate groups bound to acyclic carbon atoms of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C333/02—Monothiocarbamic acids; Derivatives thereof
- C07C333/04—Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C333/14—Dithiocarbamic acids; Derivatives thereof
- C07C333/18—Esters of dithiocarbamic acids
- C07C333/20—Esters of dithiocarbamic acids having nitrogen atoms of dithiocarbamate groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/06—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms
- C07C335/08—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2013520149A JP2013533266A (ja) | 2010-07-23 | 2011-07-20 | イソチオシアネート及びそれらの誘導体の合成方法並びにその使用 |
EP11734106.5A EP2595953A1 (fr) | 2010-07-23 | 2011-07-20 | Procede de synthese d'isothiocyanates et leurs derives et utilisations de ceux-ci |
KR1020137003904A KR20130038929A (ko) | 2010-07-23 | 2011-07-20 | 이소티오시아네이트 및 이의 유도체의 합성 방법, 및 이의 용도 |
AU2011281617A AU2011281617B2 (en) | 2010-07-23 | 2011-07-20 | Process for the synthesis of isothiocyanates and derivatives thereof and uses of same |
US13/811,600 US20130142739A1 (en) | 2010-07-23 | 2011-07-20 | Process for the synthesis of isothiocyanates and derivatives thereof and uses of same |
CN2011800351252A CN103025710A (zh) | 2010-07-23 | 2011-07-20 | 用于合成异硫氰酸酯及其衍生物的方法以及其用途 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BE2010/0456A BE1019431A3 (fr) | 2010-07-23 | 2010-07-23 | Procede de synthese d'isothiocyanates et leurs derives et utilisations de ceux-ci. |
BE2010/0456 | 2010-07-23 |
Publications (1)
Publication Number | Publication Date |
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WO2012010644A1 true WO2012010644A1 (fr) | 2012-01-26 |
Family
ID=43531176
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Application Number | Title | Priority Date | Filing Date |
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PCT/EP2011/062477 WO2012010644A1 (fr) | 2010-07-23 | 2011-07-20 | Procede de synthese d'isothiocyanates et leurs derives et utilisations de ceux-ci |
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Country | Link |
---|---|
US (1) | US20130142739A1 (fr) |
EP (1) | EP2595953A1 (fr) |
JP (1) | JP2013533266A (fr) |
CN (1) | CN103025710A (fr) |
AU (1) | AU2011281617B2 (fr) |
BE (1) | BE1019431A3 (fr) |
TW (1) | TW201206422A (fr) |
WO (1) | WO2012010644A1 (fr) |
Cited By (22)
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CN102775336A (zh) * | 2012-08-20 | 2012-11-14 | 常州大学 | 萝卜硫素衍生物及其制备方法和用途 |
CN103159691A (zh) * | 2011-12-19 | 2013-06-19 | 天津市国际生物医药联合研究院 | 异硫氰酸酯类化合物的制备及应用 |
EP2725907A1 (fr) * | 2011-06-28 | 2014-05-07 | The William M. Yarbrough Foundation | Méthode de traitement de l'eczéma |
KR101525019B1 (ko) * | 2012-10-19 | 2015-06-10 | 한국과학기술연구원 | Nrf2 활성화능을 갖는 신규 화합물, 이를 포함하는 약학적 조성물 |
US9636320B2 (en) | 2012-07-26 | 2017-05-02 | The William M. Yarbrough Foundation | Method for treating skin cancer |
US9771322B2 (en) | 2011-01-03 | 2017-09-26 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactant and associated method of use |
US9839621B2 (en) | 2012-07-26 | 2017-12-12 | The William M. Yarbrough Foundation | Method for treating bladder cancer |
US9949943B2 (en) | 2012-07-26 | 2018-04-24 | The William M. Yarbrough Foundation | Method for treating neurodegenerative diseases |
US9962361B2 (en) | 2011-01-03 | 2018-05-08 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactants, formulations incorporating the same, and associated methods of use |
US10080734B2 (en) | 2012-07-26 | 2018-09-25 | The William M. Yarbrough Foundation | Method for treating autism and other neurodevelopmental disorders |
US10273205B2 (en) | 2011-01-03 | 2019-04-30 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactants, formulations incorporating isothiocyanate functional surfactants and associated methods for treating biofilms |
US10308599B2 (en) | 2011-01-03 | 2019-06-04 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactants, formulations incorporating the same, and associated methods of use |
US10335387B2 (en) | 2012-07-26 | 2019-07-02 | The William M. Yarbrough Foundation | Method for treating infectious diseases with isothiocyanate functional compounds |
US10434081B2 (en) | 2012-07-26 | 2019-10-08 | The William M. Yarbrough Foundation | Inhibitors of macrophage migration inhibitory factor |
US10434082B2 (en) | 2012-07-26 | 2019-10-08 | The William M. Yarbrough Foundation | Isothiocyanate functional compounds augmented with secondary antineoplastic medicaments and associated methods for treating neoplasms |
US10441561B2 (en) | 2012-07-26 | 2019-10-15 | The William M. Yanbrough Foundation | Method for treating benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer |
US10532039B2 (en) | 2011-02-08 | 2020-01-14 | The William M. Yarbrough Foundation | Method for treating psoriasis |
US10640464B2 (en) | 2011-01-03 | 2020-05-05 | The William M. Yarbrough Foundation | Use of isothiocyanate functional surfactants as Nrf2 inducers to treat epidermolysis bullosa simplex and related diseases |
US10647668B2 (en) | 2011-01-03 | 2020-05-12 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactant and associated method of use |
WO2021214188A1 (fr) | 2020-04-23 | 2021-10-28 | Vio Chemicals Ag | Compositions pour stabiliser un isothiocyanate |
US11279674B2 (en) | 2011-01-03 | 2022-03-22 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactant and associated method of use |
US11407713B2 (en) | 2011-01-03 | 2022-08-09 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactants, formulations incorporating the same, and associated methods of use |
Families Citing this family (4)
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CN104710337B (zh) * | 2015-02-12 | 2016-11-23 | 领思科技(大连)有限公司 | 异硫氰酸酯类化合物及其应用 |
CN107034245B (zh) * | 2016-02-04 | 2019-12-31 | 中国科学院微生物研究所 | 一种用微生物酶法合成苄基异硫氰酸酯的方法 |
CN106496086B (zh) * | 2016-10-10 | 2018-11-06 | 沈阳药科大学 | 4-甲磺酰丁基异硫氰酸酯的合成方法 |
CN111875524A (zh) * | 2020-07-17 | 2020-11-03 | 西安近代化学研究所 | 一种碱催化制备异硫氰酸酯的方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2124786A5 (fr) * | 1971-02-05 | 1972-09-22 | Degussa | |
US5411986A (en) * | 1993-03-12 | 1995-05-02 | The Johns Hopkins University | Chemoprotective isothiocyanates |
WO2002058664A1 (fr) | 2001-01-26 | 2002-08-01 | Lmd | Utilisation d'un isothiocyanate, d'un thiocyanate ou de leur melange en tant que depigmentant |
US20080027129A1 (en) * | 2006-06-20 | 2008-01-31 | L'oreal | Administration of 3H-1, 2-dithiole-3-thione, anethole dithiolethione, sulforaphane, phenethyl isothiocyanate, 6-(methylsulfinyl)hexyl isothiocyanate and allyl isothiocyanate for the treatment of canities |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2845599B1 (fr) * | 2002-10-11 | 2005-01-07 | Lmd | Medicament comprenant une thiouree pour son utilisation en tant que depigmentant |
-
2010
- 2010-07-23 BE BE2010/0456A patent/BE1019431A3/fr active
-
2011
- 2011-07-20 JP JP2013520149A patent/JP2013533266A/ja active Pending
- 2011-07-20 AU AU2011281617A patent/AU2011281617B2/en not_active Ceased
- 2011-07-20 EP EP11734106.5A patent/EP2595953A1/fr not_active Withdrawn
- 2011-07-20 US US13/811,600 patent/US20130142739A1/en not_active Abandoned
- 2011-07-20 WO PCT/EP2011/062477 patent/WO2012010644A1/fr active Application Filing
- 2011-07-20 CN CN2011800351252A patent/CN103025710A/zh active Pending
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2124786A5 (fr) * | 1971-02-05 | 1972-09-22 | Degussa | |
US5411986A (en) * | 1993-03-12 | 1995-05-02 | The Johns Hopkins University | Chemoprotective isothiocyanates |
WO2002058664A1 (fr) | 2001-01-26 | 2002-08-01 | Lmd | Utilisation d'un isothiocyanate, d'un thiocyanate ou de leur melange en tant que depigmentant |
US20080027129A1 (en) * | 2006-06-20 | 2008-01-31 | L'oreal | Administration of 3H-1, 2-dithiole-3-thione, anethole dithiolethione, sulforaphane, phenethyl isothiocyanate, 6-(methylsulfinyl)hexyl isothiocyanate and allyl isothiocyanate for the treatment of canities |
Non-Patent Citations (1)
Title |
---|
HOU X ET AL: "Dithiocarbamic acid esters as anticancer agent. Part 1: 4-Substituted-piperazine-1-carbodithioic acid 3-cyano-3,3-diphenyl-propyl esters", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, PERGAMON, ELSEVIER SCIENCE, GB, vol. 16, no. 16, 15 August 2006 (2006-08-15), pages 4214 - 4219, XP025107440, ISSN: 0960-894X, [retrieved on 20060815], DOI: DOI:10.1016/J.BMCL.2006.05.085 * |
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Also Published As
Publication number | Publication date |
---|---|
AU2011281617A1 (en) | 2013-01-24 |
EP2595953A1 (fr) | 2013-05-29 |
TW201206422A (en) | 2012-02-16 |
JP2013533266A (ja) | 2013-08-22 |
US20130142739A1 (en) | 2013-06-06 |
CN103025710A (zh) | 2013-04-03 |
BE1019431A3 (fr) | 2012-07-03 |
AU2011281617B2 (en) | 2015-05-14 |
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