DK172106B1 - Ny fremgangsmåde og mellemprodukter og anvendelse heraf til syntese af levodopa - Google Patents
Ny fremgangsmåde og mellemprodukter og anvendelse heraf til syntese af levodopa Download PDFInfo
- Publication number
- DK172106B1 DK172106B1 DK342489A DK342489A DK172106B1 DK 172106 B1 DK172106 B1 DK 172106B1 DK 342489 A DK342489 A DK 342489A DK 342489 A DK342489 A DK 342489A DK 172106 B1 DK172106 B1 DK 172106B1
- Authority
- DK
- Denmark
- Prior art keywords
- amino
- formula
- dimethoxyphenyl
- propionitrile
- acid
- Prior art date
Links
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 title claims description 30
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 title claims description 26
- 238000000034 method Methods 0.000 title claims description 15
- 230000015572 biosynthetic process Effects 0.000 title claims description 14
- 238000003786 synthesis reaction Methods 0.000 title claims description 12
- 229960004502 levodopa Drugs 0.000 title description 19
- 239000000543 intermediate Substances 0.000 title description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 54
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 36
- 239000007864 aqueous solution Substances 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 21
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 18
- 239000000908 ammonium hydroxide Substances 0.000 claims description 18
- -1 alkali metal cyanide Chemical class 0.000 claims description 17
- 239000011541 reaction mixture Substances 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- GFOKWNNFJZNEEM-UHFFFAOYSA-N 2-amino-3-(3,4-dimethoxyphenyl)propanenitrile Chemical compound COC1=CC=C(CC(N)C#N)C=C1OC GFOKWNNFJZNEEM-UHFFFAOYSA-N 0.000 claims description 13
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 11
- 238000009835 boiling Methods 0.000 claims description 10
- 238000003776 cleavage reaction Methods 0.000 claims description 10
- 230000007062 hydrolysis Effects 0.000 claims description 10
- 238000006460 hydrolysis reaction Methods 0.000 claims description 10
- 230000007017 scission Effects 0.000 claims description 10
- DTEAZXOXMQRHNO-UHFFFAOYSA-N 2-amino-3-(3,4-dimethoxyphenyl)propanenitrile;(7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methanesulfonic acid Chemical compound COC1=CC=C(CC(N)C#N)C=C1OC.C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C DTEAZXOXMQRHNO-UHFFFAOYSA-N 0.000 claims description 9
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 claims description 9
- XJFWTMDNCNIFKJ-UHFFFAOYSA-N 2-amino-3-(3,4-dimethoxyphenyl)propanenitrile;hydrochloride Chemical compound Cl.COC1=CC=C(CC(N)C#N)C=C1OC XJFWTMDNCNIFKJ-UHFFFAOYSA-N 0.000 claims description 8
- 229910052783 alkali metal Inorganic materials 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 230000017858 demethylation Effects 0.000 claims description 6
- 238000010520 demethylation reaction Methods 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 235000019270 ammonium chloride Nutrition 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 150000004820 halides Chemical class 0.000 claims description 5
- RIVVYJWUHXMGSK-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)acetaldehyde Chemical compound COC1=CC=C(CC=O)C=C1OC RIVVYJWUHXMGSK-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 150000003863 ammonium salts Chemical class 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical group N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000003495 polar organic solvent Substances 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 150000001350 alkyl halides Chemical class 0.000 claims description 2
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 claims description 2
- UYRNFBHAWUOWGM-UHFFFAOYSA-N 2-(3,4-dihydroxyphenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=C(O)C(O)=C1 UYRNFBHAWUOWGM-UHFFFAOYSA-N 0.000 claims 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 1
- 238000010790 dilution Methods 0.000 claims 1
- 239000012895 dilution Substances 0.000 claims 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 125000005219 aminonitrile group Chemical group 0.000 description 8
- 239000007787 solid Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229960003767 alanine Drugs 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 2
- 229960004441 tyrosine Drugs 0.000 description 2
- YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 1
- UFEIDPFGICDUHT-AWEZNQCLSA-N (2s)-2-benzamido-3-(3,4-dimethoxyphenyl)propanoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C[C@@H](C(O)=O)NC(=O)C1=CC=CC=C1 UFEIDPFGICDUHT-AWEZNQCLSA-N 0.000 description 1
- DSSYKIVIOFKYAU-MHPPCMCBSA-N (4r)-4,7,7-trimethylbicyclo[2.2.1]heptan-3-one Chemical compound C1C[C@@]2(C)C(=O)CC1C2(C)C DSSYKIVIOFKYAU-MHPPCMCBSA-N 0.000 description 1
- GAQWDBUWBUOFLS-UHFFFAOYSA-N (7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methanesulfonic acid;hydrate Chemical compound O.C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C GAQWDBUWBUOFLS-UHFFFAOYSA-N 0.000 description 1
- 229930007886 (R)-camphor Natural products 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- OZDAOHVKBFBBMZ-UHFFFAOYSA-N 2-aminopentanedioic acid;hydrate Chemical compound O.OC(=O)C(N)CCC(O)=O OZDAOHVKBFBBMZ-UHFFFAOYSA-N 0.000 description 1
- LQQFFJFGLSKYIR-UHFFFAOYSA-N 3,4-dihydroxyphenylpyruvic acid Chemical class OC(=O)C(=O)CC1=CC=C(O)C(O)=C1 LQQFFJFGLSKYIR-UHFFFAOYSA-N 0.000 description 1
- FBTSQILOGYXGMD-LURJTMIESA-N 3-nitro-L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C([N+]([O-])=O)=C1 FBTSQILOGYXGMD-LURJTMIESA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001514 alkali metal chloride Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 229940125688 antiparkinson agent Drugs 0.000 description 1
- RBFQJDQYXXHULB-UHFFFAOYSA-N arsane Chemical compound [AsH3] RBFQJDQYXXHULB-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 1
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- VKDBLXQITPBAAG-UHFFFAOYSA-N propanenitrile;hydrochloride Chemical compound Cl.CCC#N VKDBLXQITPBAAG-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000010956 selective crystallization Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Classifications
-
- 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
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/30—Preparation of optical isomers
- C07C227/34—Preparation of optical isomers by separation of optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
- C07C255/43—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms the carbon skeleton being further substituted by singly-bound oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT8821322A IT1226902B (it) | 1988-07-12 | 1988-07-12 | Processo per la sintesi del levodopa |
| IT2132288 | 1988-07-12 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK342489D0 DK342489D0 (da) | 1989-07-11 |
| DK342489A DK342489A (da) | 1990-01-13 |
| DK172106B1 true DK172106B1 (da) | 1997-10-27 |
Family
ID=11180092
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK342489A DK172106B1 (da) | 1988-07-12 | 1989-07-11 | Ny fremgangsmåde og mellemprodukter og anvendelse heraf til syntese af levodopa |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US4962223A (hu) |
| EP (1) | EP0357565B1 (hu) |
| JP (1) | JP2507069B2 (hu) |
| KR (1) | KR960004185B1 (hu) |
| AR (1) | AR248267A1 (hu) |
| AT (1) | ATE111439T1 (hu) |
| AU (1) | AU615083B2 (hu) |
| CA (1) | CA1338672C (hu) |
| DD (1) | DD284674A5 (hu) |
| DE (1) | DE68918207T2 (hu) |
| DK (1) | DK172106B1 (hu) |
| ES (1) | ES2063837T3 (hu) |
| FI (1) | FI101534B1 (hu) |
| HU (1) | HU203318B (hu) |
| IE (1) | IE65956B1 (hu) |
| IL (1) | IL90844A0 (hu) |
| IT (1) | IT1226902B (hu) |
| NO (1) | NO174293C (hu) |
| NZ (1) | NZ229910A (hu) |
| PL (1) | PL160103B1 (hu) |
| PT (1) | PT91144B (hu) |
| YU (1) | YU47907B (hu) |
| ZA (1) | ZA895255B (hu) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5459145A (en) * | 1988-01-19 | 1995-10-17 | Pfizer Inc. | Calcium independent camp phosphodiesterase inhibitor antidepressant |
| IT1226903B (it) * | 1988-07-12 | 1991-02-21 | Mini Ricerca Scient Tecnolog | Processo per la sintesi di aminoacidi otticamente attivi |
| US5395935A (en) * | 1992-05-08 | 1995-03-07 | Pfizer Inc. | Endo-bicyclo[2.2.1]heptan-2-ol and derived pharmaceutical agents |
| DE19502967A1 (de) * | 1995-01-31 | 1996-08-01 | Basf Ag | Verfahren zur Racemattrennung von 2-Aryl-2-omega-alkylaminoalkannitrilen |
| JP3634207B2 (ja) * | 1999-09-14 | 2005-03-30 | 独立行政法人科学技術振興機構 | 光学活性なα−アミノニトリル並びにα−アミノ酸類の製造方法 |
| US20040002615A1 (en) * | 2002-06-28 | 2004-01-01 | Allen David Robert | Preparation of chiral amino-nitriles |
| US20040180086A1 (en) * | 2002-10-11 | 2004-09-16 | Zebunnissa Ramtoola | Gastro-retentive levodopa delivery form |
| DE10261807A1 (de) | 2002-12-19 | 2004-07-01 | Turicum Drug Development Ag | Deuterierte Catecholaminderivate sowie diese Verbindungen enthaltende Arzneimittel |
| WO2004069146A2 (en) * | 2003-02-07 | 2004-08-19 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | L-dopa amide derivatives and uses thereof |
| UA97795C2 (uk) | 2006-02-17 | 2012-03-26 | Бьордз Фарма Гмбх Бероліна Інновейтів Ресерч Унд Девелопмент Сервісіз | Дейтеровані похідні катехоламіну і медикаменти, що містять згадані сполуки |
| US10258585B2 (en) | 2014-03-13 | 2019-04-16 | Neuroderm, Ltd. | DOPA decarboxylase inhibitor compositions |
| HRP20201948T1 (hr) | 2014-03-13 | 2021-01-22 | Neuroderm Ltd | Pripravci inhibitora dopa-dekarbokilaze |
| DK3856196T3 (da) | 2018-09-28 | 2024-02-19 | Univ Griffith | Phenylpropionsyrederivater til modulation af patogen aktivitet |
| US11331293B1 (en) | 2020-11-17 | 2022-05-17 | Neuroderm, Ltd. | Method for treatment of Parkinson's disease |
| US11213502B1 (en) | 2020-11-17 | 2022-01-04 | Neuroderm, Ltd. | Method for treatment of parkinson's disease |
| US11844754B2 (en) | 2020-11-17 | 2023-12-19 | Neuroderm, Ltd. | Methods for treatment of Parkinson's disease |
| US12161612B2 (en) | 2023-04-14 | 2024-12-10 | Neuroderm, Ltd. | Methods and compositions for reducing symptoms of Parkinson's disease |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA504449A (en) * | 1954-07-20 | C. Britton Edgar | Alpha-amino-beta-alkoxy-butyronitriles and method of making same | |
| BE638485A (hu) * | 1962-10-11 | |||
| US3845076A (en) * | 1971-04-20 | 1974-10-29 | Sagami Chem Res | Method of preparing aldehydes |
| JPS4920305A (hu) * | 1972-06-21 | 1974-02-22 | ||
| HU165026B (hu) * | 1972-08-11 | 1974-06-28 | ||
| US4072698A (en) * | 1976-12-02 | 1978-02-07 | The Upjohn Company | Resolution of aminonitriles |
| YU93877A (en) * | 1977-04-08 | 1982-06-30 | Krka | Process for the resolution of racemic alpha-aminonitrils |
| IL59048A (en) * | 1979-12-27 | 1984-01-31 | Plantex Ltd | Process for the preparation of alpha-amino-3-phenyl-propionitriles and novel benzylidene amino acetonitriles as intermediates therefor |
| DE3002543A1 (de) * | 1980-01-25 | 1981-07-30 | Basf Ag, 6700 Ludwigshafen | 4-tert.-butoxyphenylglycinnitril sowie verfahren zur herstellung von d-(-)- und l-(+)-4-hydroxyphenylglycin |
| JPS56115749A (en) * | 1980-02-18 | 1981-09-11 | Sagami Chem Res Center | Dopa derivative |
| JPS61275253A (ja) * | 1985-05-30 | 1986-12-05 | Nippon Kayaku Co Ltd | ３−（３，４−ジヒドロキシフエニル）−２−メチルアラニンの製造法 |
| FR2614626B1 (fr) * | 1987-04-30 | 1989-07-21 | Ranoux Claude | Conteneur pour fecondation des ovocytes et replacement des embryons chez l'homme et l'animal |
-
1988
- 1988-07-12 IT IT8821322A patent/IT1226902B/it active
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1989
- 1989-07-03 US US07/375,131 patent/US4962223A/en not_active Expired - Fee Related
- 1989-07-03 IL IL90844A patent/IL90844A0/xx not_active IP Right Cessation
- 1989-07-07 ES ES89830316T patent/ES2063837T3/es not_active Expired - Lifetime
- 1989-07-07 AT AT89830316T patent/ATE111439T1/de not_active IP Right Cessation
- 1989-07-07 DE DE68918207T patent/DE68918207T2/de not_active Expired - Fee Related
- 1989-07-07 EP EP89830316A patent/EP0357565B1/en not_active Expired - Lifetime
- 1989-07-11 ZA ZA895255A patent/ZA895255B/xx unknown
- 1989-07-11 DD DD89330685A patent/DD284674A5/de not_active IP Right Cessation
- 1989-07-11 HU HU893486A patent/HU203318B/hu not_active IP Right Cessation
- 1989-07-11 NZ NZ229910A patent/NZ229910A/en unknown
- 1989-07-11 IE IE222789A patent/IE65956B1/en not_active IP Right Cessation
- 1989-07-11 FI FI893368A patent/FI101534B1/fi not_active IP Right Cessation
- 1989-07-11 NO NO892861A patent/NO174293C/no not_active IP Right Cessation
- 1989-07-11 PL PL89280528A patent/PL160103B1/pl unknown
- 1989-07-11 DK DK342489A patent/DK172106B1/da not_active IP Right Cessation
- 1989-07-11 AR AR89314355A patent/AR248267A1/es active
- 1989-07-12 JP JP1180152A patent/JP2507069B2/ja not_active Expired - Lifetime
- 1989-07-12 CA CA000605420A patent/CA1338672C/en not_active Expired - Fee Related
- 1989-07-12 KR KR1019890009905A patent/KR960004185B1/ko not_active Expired - Fee Related
- 1989-07-12 AU AU38057/89A patent/AU615083B2/en not_active Ceased
- 1989-07-12 PT PT91144A patent/PT91144B/pt not_active IP Right Cessation
- 1989-07-12 YU YU139989A patent/YU47907B/sh unknown
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| B1 | Patent granted (law 1993) | ||
| PBP | Patent lapsed |