ES2960805T3 - Compuesto químico útil como intermediario para preparar un inhibidor de catecol-o-metiltransferasa - Google Patents
Compuesto químico útil como intermediario para preparar un inhibidor de catecol-o-metiltransferasa Download PDFInfo
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- ES2960805T3 ES2960805T3 ES19194756T ES19194756T ES2960805T3 ES 2960805 T3 ES2960805 T3 ES 2960805T3 ES 19194756 T ES19194756 T ES 19194756T ES 19194756 T ES19194756 T ES 19194756T ES 2960805 T3 ES2960805 T3 ES 2960805T3
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- 150000001875 compounds Chemical class 0.000 title claims description 119
- 239000003543 catechol methyltransferase inhibitor Substances 0.000 title abstract description 11
- 229940099362 Catechol O methyltransferase inhibitor Drugs 0.000 title abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 49
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 173
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 122
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 91
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 90
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 86
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 75
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 70
- 239000000203 mixture Substances 0.000 claims description 61
- 229910001868 water Inorganic materials 0.000 claims description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 47
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 43
- 235000019253 formic acid Nutrition 0.000 claims description 43
- 238000006243 chemical reaction Methods 0.000 claims description 41
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 37
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 35
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 29
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 24
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 22
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 18
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 17
- 229910017604 nitric acid Inorganic materials 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 15
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- PPQJCISYYXZCAE-UHFFFAOYSA-N 1,10-phenanthroline;hydrate Chemical compound O.C1=CN=C2C3=NC=CC=C3C=CC2=C1 PPQJCISYYXZCAE-UHFFFAOYSA-N 0.000 claims description 11
- 239000003960 organic solvent Substances 0.000 claims description 10
- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 claims description 10
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 claims description 10
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 claims description 10
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 9
- 229910006124 SOCl2 Inorganic materials 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 238000010520 demethylation reaction Methods 0.000 claims description 8
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 230000008878 coupling Effects 0.000 claims description 6
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- -1 aluminum chloride Chemical class 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 230000017858 demethylation Effects 0.000 claims description 4
- 238000002955 isolation Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- BVWTXUYLKBHMOX-UHFFFAOYSA-N methyl vanillate Chemical compound COC(=O)C1=CC=C(O)C(OC)=C1 BVWTXUYLKBHMOX-UHFFFAOYSA-N 0.000 claims description 4
- 239000002841 Lewis acid Substances 0.000 claims description 3
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- 150000007517 lewis acids Chemical class 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- 239000000460 chlorine Substances 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- CCVKPWUMYBYHCD-UHFFFAOYSA-N oxolane;pyridine Chemical compound C1CCOC1.C1=CC=NC=C1 CCVKPWUMYBYHCD-UHFFFAOYSA-N 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- 239000011541 reaction mixture Substances 0.000 description 32
- 229960000583 acetic acid Drugs 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
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- 238000002425 crystallisation Methods 0.000 description 24
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 238000001953 recrystallisation Methods 0.000 description 21
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- 239000012043 crude product Substances 0.000 description 17
- 230000003197 catalytic effect Effects 0.000 description 15
- 239000000543 intermediate Substances 0.000 description 15
- 238000004821 distillation Methods 0.000 description 14
- 239000000463 material Substances 0.000 description 13
- 239000008194 pharmaceutical composition Substances 0.000 description 12
- 230000008859 change Effects 0.000 description 11
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- 239000008367 deionised water Substances 0.000 description 11
- 229910021641 deionized water Inorganic materials 0.000 description 11
- AGMWEOLWLPKJFM-UHFFFAOYSA-N 4-[3-(2,5-dichloro-4,6-dimethylpyridin-3-yl)-1,2,4-oxadiazol-5-yl]-2-methoxy-6-nitrophenol Chemical compound [O-][N+](=O)C1=C(O)C(OC)=CC(C=2ON=C(N=2)C=2C(=NC(C)=C(Cl)C=2C)Cl)=C1 AGMWEOLWLPKJFM-UHFFFAOYSA-N 0.000 description 10
- AEDVAGWYAKIOIM-UHFFFAOYSA-N 4-hydroxy-3-methoxy-5-nitrobenzoic acid Chemical compound COC1=CC(C(O)=O)=CC([N+]([O-])=O)=C1O AEDVAGWYAKIOIM-UHFFFAOYSA-N 0.000 description 10
- ASOADIZOVZTJSR-UHFFFAOYSA-N opicapone Chemical compound CC1=C(Cl)C(C)=[N+]([O-])C(Cl)=C1C1=NOC(C=2C=C(C(O)=C(O)C=2)[N+]([O-])=O)=N1 ASOADIZOVZTJSR-UHFFFAOYSA-N 0.000 description 10
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- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
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- HVGGGVAREUUJQV-CHHVJCJISA-N (4z)-4-[3-(2,5-dichloro-4,6-dimethyl-1-oxidopyridin-1-ium-3-yl)-2h-1,2,4-oxadiazol-5-ylidene]-2-hydroxy-6-nitrocyclohexa-2,5-dien-1-one Chemical compound CC1=C(Cl)C(C)=[N+]([O-])C(Cl)=C1C(NO1)=N\C1=C\1C=C([N+]([O-])=O)C(=O)C(O)=C/1 HVGGGVAREUUJQV-CHHVJCJISA-N 0.000 description 7
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- 229950001673 opicapone Drugs 0.000 description 7
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 7
- MIQPIUSUKVNLNT-UHFFFAOYSA-N tolcapone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC(O)=C(O)C([N+]([O-])=O)=C1 MIQPIUSUKVNLNT-UHFFFAOYSA-N 0.000 description 7
- 229960004603 tolcapone Drugs 0.000 description 7
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 5
- MDAYSECURTYDPB-UHFFFAOYSA-N 4-hydroxy-3-methoxy-5-nitrobenzoyl chloride Chemical compound COC1=CC(C(Cl)=O)=CC([N+]([O-])=O)=C1O MDAYSECURTYDPB-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 102000006378 Catechol O-methyltransferase Human genes 0.000 description 5
- 108020002739 Catechol O-methyltransferase Proteins 0.000 description 5
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 5
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 5
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- WRFGQLDAKOYZHS-UHFFFAOYSA-N 2,5-dichloro-n'-hydroxy-4,6-dimethylpyridine-3-carboximidamide Chemical compound CC1=NC(Cl)=C(C(N)=NO)C(C)=C1Cl WRFGQLDAKOYZHS-UHFFFAOYSA-N 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
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- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 229940042400 direct acting antivirals phosphonic acid derivative Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- JRURYQJSLYLRLN-BJMVGYQFSA-N entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 description 1
- 229960003337 entacapone Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- SYJRVVFAAIUVDH-UHFFFAOYSA-N ipa isopropanol Chemical compound CC(C)O.CC(C)O SYJRVVFAAIUVDH-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 150000003007 phosphonic acid derivatives Chemical class 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
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- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Public Health (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
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| US201261593625P | 2012-02-01 | 2012-02-01 | |
| GBGB1201758.8A GB201201758D0 (en) | 2012-02-01 | 2012-02-01 | Chemical compounds and processes |
| US201261718589P | 2012-10-25 | 2012-10-25 |
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| AU2006272978B2 (en) | 2005-07-26 | 2012-06-07 | Bial - Portela & Ca, S.A. | Nitrocatechol derivatives as COMT inhibitors |
| EP1845097A1 (en) | 2006-04-10 | 2007-10-17 | Portela & Ca., S.A. | Oxadiazole derivatives as COMT inhibitors |
| CN101631548B (zh) | 2007-01-31 | 2014-08-27 | 比艾尔-坡特拉有限公司 | Comt抑制剂的单次药物剂量单元和药物组合物 |
| AU2009226221A1 (en) | 2008-03-17 | 2009-09-24 | Bial - Portela & Ca., S.A. | Crystal forms of 5- [3- (2, 5-dichloro-4, 6-dimethyl-1-oxy-pyridine-3-yl) [1,2,3] oxadiazol-5-yl] -3-nit robenzene-1, 2-diol |
| KR102023255B1 (ko) | 2009-04-01 | 2019-09-19 | 바이알 - 포르텔라 앤드 씨에이 에스에이 | 니트로카테콜 유도체를 포함하는 제약 제제 및 그의 제조 방법 |
| US20140045900A1 (en) | 2011-02-11 | 2014-02-13 | Bial-Portela & Ca, S.A. | Administration regime for nitrocatechols |
| BR112014014341A2 (pt) * | 2011-12-13 | 2017-08-22 | Bial Portela & Ca Sa | Intermediário metilado, seu método de preparação e seus usos, e composição farmacêutica |
| WO2016083863A1 (en) | 2014-11-28 | 2016-06-02 | Bial - Portela & Ca, S.A. | Medicaments for slowing parkinson's disease |
| GB2563858A (en) * | 2017-06-27 | 2019-01-02 | Azad Pharmaceutical Ingredients Ag | New route of synthesis for opicapone |
| KR20200100075A (ko) * | 2017-12-18 | 2020-08-25 | 유니켐 레버러토리스 리미티드 | 오피카폰 및 그의 중간체의 제조방법 |
| WO2020072886A1 (en) | 2018-10-05 | 2020-04-09 | Neurocrine Biosciences, Inc. | Methods for the administration of comt inhibitors |
| EP3860602A1 (en) | 2018-10-05 | 2021-08-11 | Neurocrine Biosciences, Inc. | Methods for the administration of comt inhibitors |
| CN109529881A (zh) * | 2018-11-12 | 2019-03-29 | 刘晓菊 | 一种治疗帕金森药物用中间体5-硝基香草酸的制备方法 |
| CN120478288A (zh) * | 2020-03-13 | 2025-08-15 | 巴尔-波特拉及康邦亚股份有限公司 | 微粉化的奥匹卡朋 |
| TW202200138A (zh) * | 2020-05-26 | 2022-01-01 | 日商小野藥品工業股份有限公司 | 包含奧匹卡朋（ｏｐｉｃａｐｏｎｅ）之錠劑 |
| GB202011709D0 (en) | 2020-07-28 | 2020-09-09 | Bial Portela & Ca Sa | Solid dispersion of opicapone |
| GB202016425D0 (en) | 2020-10-16 | 2020-12-02 | Bial Portela & Ca Sa | Treatment regimens for parkinson's disease |
| CN112375014A (zh) * | 2020-12-17 | 2021-02-19 | 重庆柳江医药科技有限公司 | 一种奥匹卡朋工艺杂质及制备方法和用途 |
| WO2022131944A1 (en) | 2020-12-17 | 2022-06-23 | Bial-Portela & Ca., S.A. | Treatment regimens for early idiopathic parkinson's disease |
| US20240300930A1 (en) * | 2021-02-26 | 2024-09-12 | Msn Laboratories Private Limited, R&D Center | Novel process for the preparation of 2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine-1-oxide |
| CN113292489B (zh) * | 2021-06-16 | 2022-08-30 | 泓博智源(开原)药业有限公司 | 二氯代二烷基烟腈的制备方法 |
| GB202204798D0 (en) | 2022-04-01 | 2022-05-18 | Bial Portela & Ca Sa | Prodrugs of opicapone |
| GB202212082D0 (en) | 2022-08-18 | 2022-10-05 | Bial Portela & Ca Sa | Treatment regimens for parkinson's disease |
| GB202219669D0 (en) | 2022-12-23 | 2023-02-08 | Bial Portela & Ca Sa | Processes and intermediates for synthesising opicapone |
| WO2024242579A1 (en) | 2023-05-25 | 2024-11-28 | Bial-Portela & Ca., S.A. | Treatment regimens for early idiopathic parkinson's disease |
| EP4727649A1 (en) * | 2023-06-19 | 2026-04-22 | Medichem, S.A. | Process for preparing opicapone |
| WO2025012643A1 (en) | 2023-07-11 | 2025-01-16 | Tay Therapeutics Limited | Compounds comprising a naphthyridine or pyridopyrimidine core as ptc read-through agents |
| CN119775271A (zh) * | 2024-12-31 | 2025-04-08 | 南京海纳医药科技股份有限公司 | 一种奥吡卡朋粗品的精制方法 |
| CN120081837A (zh) * | 2025-02-14 | 2025-06-03 | 江苏天士力帝益药业有限公司 | 一种低单杂高纯度的奥匹卡朋中间体05的制备方法 |
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| EP2259777A2 (en) | 2008-02-28 | 2010-12-15 | BIAL - Portela & Ca., S.A. | Pharmaceutical composition for poorly soluble drugs |
| AU2009226221A1 (en) | 2008-03-17 | 2009-09-24 | Bial - Portela & Ca., S.A. | Crystal forms of 5- [3- (2, 5-dichloro-4, 6-dimethyl-1-oxy-pyridine-3-yl) [1,2,3] oxadiazol-5-yl] -3-nit robenzene-1, 2-diol |
| ES2723729T3 (es) | 2008-07-29 | 2019-08-30 | Bial Portela & Ca Sa | Régimen de administración de nitrocatecoles |
| KR102023255B1 (ko) | 2009-04-01 | 2019-09-19 | 바이알 - 포르텔라 앤드 씨에이 에스에이 | 니트로카테콜 유도체를 포함하는 제약 제제 및 그의 제조 방법 |
| JP5864410B2 (ja) | 2009-04-01 | 2016-02-17 | ノヴィファーマ ソシエテ アノニム | ニトロカテコール誘導体を含む医薬製剤及びその製造方法 |
| KR101868326B1 (ko) | 2010-03-04 | 2018-06-19 | 오리온 코포레이션 | 파킨슨병의 치료를 위한 레보도파, 카르비도파 및 엔타카폰의 용도 |
| US20140045900A1 (en) | 2011-02-11 | 2014-02-13 | Bial-Portela & Ca, S.A. | Administration regime for nitrocatechols |
| BR112014014341A2 (pt) * | 2011-12-13 | 2017-08-22 | Bial Portela & Ca Sa | Intermediário metilado, seu método de preparação e seus usos, e composição farmacêutica |
-
2012
- 2012-12-12 BR BR112014014341A patent/BR112014014341A2/pt not_active Application Discontinuation
- 2012-12-12 EP EP12806720.4A patent/EP2791134B1/en active Active
- 2012-12-12 JP JP2014547135A patent/JP6456143B2/ja active Active
- 2012-12-12 DK DK12806720T patent/DK2791134T3/da active
- 2012-12-12 ES ES19194756T patent/ES2960805T3/es active Active
- 2012-12-12 WO PCT/PT2012/000048 patent/WO2013089573A1/en not_active Ceased
- 2012-12-12 US US14/365,265 patent/US9126988B2/en active Active
- 2012-12-12 PL PL12806720T patent/PL2791134T3/pl unknown
- 2012-12-12 PT PT191947563T patent/PT3604299T/pt unknown
- 2012-12-12 PT PT128067204T patent/PT2791134T/pt unknown
- 2012-12-12 ES ES12806720T patent/ES2758659T3/es active Active
- 2012-12-12 EP EP19194756.3A patent/EP3604299B1/en active Active
- 2012-12-12 RS RS20191562A patent/RS59666B1/sr unknown
- 2012-12-12 HR HRP20192133TT patent/HRP20192133T8/hr unknown
- 2012-12-12 CA CA3088684A patent/CA3088684C/en active Active
- 2012-12-12 SI SI201231703T patent/SI2791134T1/sl unknown
- 2012-12-12 HU HUE12806720A patent/HUE047856T2/hu unknown
- 2012-12-12 CA CA2858025A patent/CA2858025C/en active Active
-
2015
- 2015-07-31 US US14/814,603 patent/US9630955B2/en active Active
-
2017
- 2017-10-27 JP JP2017207738A patent/JP6721558B2/ja active Active
-
2019
- 2019-11-27 CY CY20191101241T patent/CY1122580T1/el unknown
- 2019-11-27 JP JP2019214566A patent/JP2020059729A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| BR112014014341A2 (pt) | 2017-08-22 |
| CA2858025A1 (en) | 2013-06-20 |
| EP3604299B1 (en) | 2023-07-26 |
| PT3604299T (pt) | 2023-10-31 |
| JP2015500335A (ja) | 2015-01-05 |
| EP2791134A1 (en) | 2014-10-22 |
| JP2020059729A (ja) | 2020-04-16 |
| CY1122580T1 (el) | 2021-01-27 |
| ES2758659T3 (es) | 2020-05-06 |
| PL2791134T3 (pl) | 2020-03-31 |
| JP6456143B2 (ja) | 2019-01-23 |
| SI2791134T1 (sl) | 2020-01-31 |
| RS59666B1 (sr) | 2020-01-31 |
| HUE047856T2 (hu) | 2020-05-28 |
| US9126988B2 (en) | 2015-09-08 |
| PT2791134T (pt) | 2019-12-18 |
| CA3088684C (en) | 2021-10-26 |
| CA3088684A1 (en) | 2013-06-20 |
| US9630955B2 (en) | 2017-04-25 |
| EP3604299A1 (en) | 2020-02-05 |
| HRP20192133T1 (hr) | 2020-02-21 |
| JP6721558B2 (ja) | 2020-07-15 |
| WO2013089573A1 (en) | 2013-06-20 |
| CA2858025C (en) | 2020-09-22 |
| JP2018052949A (ja) | 2018-04-05 |
| EP2791134B1 (en) | 2019-09-25 |
| US20160009700A1 (en) | 2016-01-14 |
| DK2791134T3 (da) | 2019-12-09 |
| HRP20192133T8 (hr) | 2021-02-19 |
| US20140350057A1 (en) | 2014-11-27 |
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