CA2815093C - Method for the manufacturing of naltrexone - Google Patents
Method for the manufacturing of naltrexone Download PDFInfo
- Publication number
- CA2815093C CA2815093C CA2815093A CA2815093A CA2815093C CA 2815093 C CA2815093 C CA 2815093C CA 2815093 A CA2815093 A CA 2815093A CA 2815093 A CA2815093 A CA 2815093A CA 2815093 C CA2815093 C CA 2815093C
- Authority
- CA
- Canada
- Prior art keywords
- process according
- naltrexone
- noroxymorphone
- nalmefene
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 100
- 229960003086 naltrexone Drugs 0.000 title claims abstract description 63
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 title claims abstract description 59
- 238000004519 manufacturing process Methods 0.000 title claims description 12
- 230000008569 process Effects 0.000 claims abstract description 84
- HLMSIZPQBSYUNL-IPOQPSJVSA-N Noroxymorphone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4 HLMSIZPQBSYUNL-IPOQPSJVSA-N 0.000 claims abstract description 47
- -1 cyclopropylmethyl halide Chemical class 0.000 claims abstract description 21
- 239000000203 mixture Substances 0.000 claims description 45
- WJBLNOPPDWQMCH-MBPVOVBZSA-N Nalmefene Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=C)O)CC1)O)CC1CC1 WJBLNOPPDWQMCH-MBPVOVBZSA-N 0.000 claims description 40
- 229960005297 nalmefene Drugs 0.000 claims description 39
- 239000002253 acid Substances 0.000 claims description 26
- ZFPGARUNNKGOBB-UHFFFAOYSA-N 1-Ethyl-2-pyrrolidinone Chemical compound CCN1CCCC1=O ZFPGARUNNKGOBB-UHFFFAOYSA-N 0.000 claims description 25
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 238000002156 mixing Methods 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 239000007787 solid Substances 0.000 claims description 18
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical group BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 claims description 16
- 239000003586 protic polar solvent Substances 0.000 claims description 15
- 239000002516 radical scavenger Substances 0.000 claims description 15
- 239000011541 reaction mixture Substances 0.000 claims description 14
- 238000007239 Wittig reaction Methods 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 5
- 239000003610 charcoal Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 150000004820 halides Chemical class 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims 1
- 230000029936 alkylation Effects 0.000 abstract description 8
- 238000005804 alkylation reaction Methods 0.000 abstract description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 23
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 13
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 235000019441 ethanol Nutrition 0.000 description 12
- 239000008194 pharmaceutical composition Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000012458 free base Substances 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- GYWMRGWFQPSQLK-OPHZJPRHSA-N (4r,4as,7as,12bs)-3-(cyclopropylmethyl)-7-methylidene-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol;hydron;chloride Chemical compound Cl.N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=C)O)CC1)O)CC1CC1 GYWMRGWFQPSQLK-OPHZJPRHSA-N 0.000 description 7
- 229960000677 nalmefene hydrochloride Drugs 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 239000000908 ammonium hydroxide Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 4
- 235000015497 potassium bicarbonate Nutrition 0.000 description 4
- 239000011736 potassium bicarbonate Substances 0.000 description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 208000007848 Alcoholism Diseases 0.000 description 2
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- 206010012335 Dependence Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 238000007126 N-alkylation reaction Methods 0.000 description 2
- 229940127450 Opioid Agonists Drugs 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 201000007930 alcohol dependence Diseases 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229960000913 crospovidone Drugs 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 150000004683 dihydrates Chemical group 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 239000003401 opiate antagonist Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- QMFVIJMHPXUVOL-RCGDHTHDSA-N (4r,4as,7ar,12bs)-4a,9-dihydroxy-1,2,3,4,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one;hydrochloride Chemical compound Cl.O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4 QMFVIJMHPXUVOL-RCGDHTHDSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 208000001613 Gambling Diseases 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 229940123257 Opioid receptor antagonist Drugs 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 206010034158 Pathological gambling Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 206010048010 Withdrawal syndrome Diseases 0.000 description 1
- USDJGQLNFPZEON-UHFFFAOYSA-N [[4,6-bis(hydroxymethylamino)-1,3,5-triazin-2-yl]amino]methanol Chemical compound OCNC1=NC(NCO)=NC(NCO)=N1 USDJGQLNFPZEON-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000005323 carbonate salts Chemical class 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- ZVTQWXCKQTUVPY-UHFFFAOYSA-N chloromethylcyclopropane Chemical compound ClCC1CC1 ZVTQWXCKQTUVPY-UHFFFAOYSA-N 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- JHKJQWFHNIOUKY-UHFFFAOYSA-N iodomethylcyclopropane Chemical compound ICC1CC1 JHKJQWFHNIOUKY-UHFFFAOYSA-N 0.000 description 1
- 229960004592 isopropanol Drugs 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 229910000032 lithium hydrogen carbonate Inorganic materials 0.000 description 1
- 230000007056 liver toxicity Effects 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 229950010675 nalmefene hydrochloride dihydrate Drugs 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- HRQDCDQDOPSGBR-UHFFFAOYSA-M sodium;octane-1-sulfonate Chemical compound [Na+].CCCCCCCCS([O-])(=O)=O HRQDCDQDOPSGBR-UHFFFAOYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 229940086542 triethylamine Drugs 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/06—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with a hetero atom directly attached in position 14
- C07D489/08—Oxygen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory 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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41040510P | 2010-11-05 | 2010-11-05 | |
| US61/410,405 | 2010-11-05 | ||
| DKPA201001007 | 2010-11-05 | ||
| DKPA201001007 | 2010-11-05 | ||
| US201161489701P | 2011-05-25 | 2011-05-25 | |
| DKPA201100396 | 2011-05-25 | ||
| US61/489,701 | 2011-05-25 | ||
| DKPA201100396 | 2011-05-25 | ||
| PCT/DK2011/000128 WO2012059103A1 (en) | 2010-11-05 | 2011-11-04 | Method for the manufacturing of naltrexone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2815093A1 CA2815093A1 (en) | 2012-05-10 |
| CA2815093C true CA2815093C (en) | 2019-08-06 |
Family
ID=45001588
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2815093A Active CA2815093C (en) | 2010-11-05 | 2011-11-04 | Method for the manufacturing of naltrexone |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP2635586B1 (enExample) |
| JP (2) | JP6246589B2 (enExample) |
| AP (1) | AP3415A (enExample) |
| AU (1) | AU2011325563B2 (enExample) |
| CA (1) | CA2815093C (enExample) |
| CY (1) | CY1118742T1 (enExample) |
| DK (1) | DK2635586T3 (enExample) |
| EA (1) | EA022266B1 (enExample) |
| ES (1) | ES2620660T3 (enExample) |
| HR (1) | HRP20170379T1 (enExample) |
| HU (1) | HUE033596T2 (enExample) |
| LT (1) | LT2635586T (enExample) |
| ME (1) | ME02621B (enExample) |
| MX (1) | MX2013005009A (enExample) |
| PL (1) | PL2635586T3 (enExample) |
| PT (1) | PT2635586T (enExample) |
| RS (1) | RS55777B1 (enExample) |
| SI (1) | SI2635586T1 (enExample) |
| SM (1) | SMT201700177T1 (enExample) |
| WO (1) | WO2012059103A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140005217A1 (en) | 2012-06-27 | 2014-01-02 | H. Lundbeck A/S | Nalmefene for reduction of alcohol consumption in specific target populations |
| AR096851A1 (es) | 2013-07-11 | 2016-02-03 | H Lundbeck As | Sales que no forman hidratos ni solvatos de nalmefeno |
| AU2014368548B2 (en) | 2013-12-20 | 2019-09-19 | H. Lundbeck A/S | Use of an opioid receptor antagonist with kappa-activity and vortioxetine for treatment of depressive disorder with melancholic features |
| MX2016013889A (es) | 2014-04-22 | 2017-03-09 | Otsuka Pharma Co Ltd | Medicamento. |
| US9701688B2 (en) * | 2014-05-05 | 2017-07-11 | Noramco, Inc. | Process for the preparation of opioid compounds |
| US9701687B2 (en) * | 2014-05-05 | 2017-07-11 | Noramco, Inc. | Process for the preparation of opioid compounds |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4535157A (en) | 1983-11-01 | 1985-08-13 | Key Pharmaceuticals, Inc. | Process for making 6-desoxy-6-methylenenaloxone and 6-desoxy-6-methylenenaltrexone |
| US4751307A (en) | 1985-01-17 | 1988-06-14 | Mallinckrodt, Inc. | Wittig-reaction processes |
| ATE178329T1 (de) * | 1989-10-16 | 1999-04-15 | Us Health | Totale synthese von northebain-, normorphin-, noroxymorphon-enantiomeren und -derivaten via n- nor-zwischenverbindungen |
| FR2906252B1 (fr) | 2006-09-21 | 2008-11-28 | Sanofi Aventis Sa | Procede de preparation d'halogenures de n-aklyl naltrexone |
| WO2008138383A1 (de) | 2007-05-16 | 2008-11-20 | Cilag Ag | Verfahren zur herstellung von n-methylnaltrexonbromid |
| ES2566559T3 (es) | 2008-09-30 | 2016-04-13 | Mallinckrodt Llc | Procesos para la alquilación de grupos amino secundarios de derivados de morfinano |
| JP5794980B2 (ja) | 2009-05-25 | 2015-10-14 | ハー・ルンドベック・アクチエゼルスカベット | ナルトレキソンからの塩酸ナルメフェンの調製 |
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2011
- 2011-11-04 HR HRP20170379TT patent/HRP20170379T1/hr unknown
- 2011-11-04 SI SI201131131A patent/SI2635586T1/sl unknown
- 2011-11-04 CA CA2815093A patent/CA2815093C/en active Active
- 2011-11-04 PL PL11785301T patent/PL2635586T3/pl unknown
- 2011-11-04 WO PCT/DK2011/000128 patent/WO2012059103A1/en not_active Ceased
- 2011-11-04 AU AU2011325563A patent/AU2011325563B2/en not_active Ceased
- 2011-11-04 AP AP2013006897A patent/AP3415A/xx active
- 2011-11-04 PT PT117853010T patent/PT2635586T/pt unknown
- 2011-11-04 LT LTEP11785301.0T patent/LT2635586T/lt unknown
- 2011-11-04 DK DK11785301.0T patent/DK2635586T3/en active
- 2011-11-04 EP EP11785301.0A patent/EP2635586B1/en active Active
- 2011-11-04 JP JP2013537002A patent/JP6246589B2/ja active Active
- 2011-11-04 HU HUE11785301A patent/HUE033596T2/hu unknown
- 2011-11-04 RS RS20170244A patent/RS55777B1/sr unknown
- 2011-11-04 EA EA201390658A patent/EA022266B1/ru not_active IP Right Cessation
- 2011-11-04 MX MX2013005009A patent/MX2013005009A/es active IP Right Grant
- 2011-11-04 ES ES11785301.0T patent/ES2620660T3/es active Active
- 2011-11-04 SM SM20170177T patent/SMT201700177T1/it unknown
- 2011-11-04 ME MEP-2017-57A patent/ME02621B/me unknown
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2016
- 2016-06-24 JP JP2016125389A patent/JP6215399B2/ja active Active
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2017
- 2017-03-17 CY CY20171100341T patent/CY1118742T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CY1118742T1 (el) | 2017-07-12 |
| AU2011325563A1 (en) | 2013-05-02 |
| DK2635586T3 (en) | 2017-03-27 |
| JP2016199566A (ja) | 2016-12-01 |
| ME02621B (me) | 2017-06-20 |
| EP2635586B1 (en) | 2017-02-08 |
| JP6246589B2 (ja) | 2017-12-13 |
| AP3415A (en) | 2015-09-30 |
| SMT201700177T1 (it) | 2017-05-08 |
| MX2013005009A (es) | 2013-08-01 |
| RS55777B1 (sr) | 2017-07-31 |
| ES2620660T3 (es) | 2017-06-29 |
| AU2011325563B2 (en) | 2015-08-20 |
| HUE033596T2 (hu) | 2017-12-28 |
| PL2635586T3 (pl) | 2017-06-30 |
| EP2635586A1 (en) | 2013-09-11 |
| HRP20170379T1 (hr) | 2017-05-05 |
| JP2013541564A (ja) | 2013-11-14 |
| JP6215399B2 (ja) | 2017-10-18 |
| AP2013006897A0 (en) | 2013-05-31 |
| SI2635586T1 (sl) | 2017-07-31 |
| LT2635586T (lt) | 2017-04-10 |
| EA022266B1 (ru) | 2015-11-30 |
| EA201390658A1 (ru) | 2013-11-29 |
| WO2012059103A1 (en) | 2012-05-10 |
| CA2815093A1 (en) | 2012-05-10 |
| PT2635586T (pt) | 2017-03-30 |
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