NO120368B - - Google Patents

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Info

Publication number: NO120368B
Authority: NO; Norway
Prior art keywords: formula; hydroxydihydronormorphinone; group; hydroxydihydronormorphine; derivative
Prior art date: 1966-01-19

Application number

NO166137A

Other languages

English (en)

Norwegian (no)

Inventor

H Blumberg

I Pachter

Z Matossian

Original Assignee

Endo Lab

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1966-01-19

Filing date

1966-12-23

Publication date

1970-10-12

1966-12-23 Application filed by Endo Lab filed Critical Endo Lab

1970-10-12 Publication of NO120368B publication Critical patent/NO120368B/no

Links

238000000034 method Methods 0.000 claims description 38
150000001875 compounds Chemical class 0.000 claims description 33
-1 2-methyl-l-propenyl group Chemical group 0.000 claims description 23
230000000202 analgesic effect Effects 0.000 claims description 16
230000003533 narcotic effect Effects 0.000 claims description 8
230000008569 process Effects 0.000 claims description 7
230000009467 reduction Effects 0.000 claims description 7
150000003839 salts Chemical class 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 6
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical class O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 6
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
125000005843 halogen group Chemical group 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
150000008064 anhydrides Chemical group 0.000 claims description 3
125000006020 2-methyl-1-propenyl group Chemical group 0.000 claims description 2
125000000217 alkyl group Chemical group 0.000 claims description 2
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
125000005228 aryl sulfonate group Chemical group 0.000 claims description 2
150000002148 esters Chemical class 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
229920002554 vinyl polymer Polymers 0.000 claims description 2
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
239000000047 product Substances 0.000 description 26
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
239000000203 mixture Substances 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 12
238000002844 melting Methods 0.000 description 12
230000008018 melting Effects 0.000 description 12
239000003887 narcotic antagonist Substances 0.000 description 11
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 description 10
239000012280 lithium aluminium hydride Substances 0.000 description 10
238000001953 recrystallisation Methods 0.000 description 9
239000012279 sodium borohydride Substances 0.000 description 9
229910000033 sodium borohydride Inorganic materials 0.000 description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
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 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
238000010992 reflux Methods 0.000 description 7
239000005977 Ethylene Substances 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
238000004519 manufacturing process Methods 0.000 description 6
238000003756 stirring Methods 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
230000036592 analgesia Effects 0.000 description 5
229940035676 analgesics Drugs 0.000 description 5
239000000730 antalgic agent Substances 0.000 description 5
239000002585 base Substances 0.000 description 5
JFWMYCVMQSLLOO-UHFFFAOYSA-N cyclobutanecarbonyl chloride Chemical compound ClC(=O)C1CCC1 JFWMYCVMQSLLOO-UHFFFAOYSA-N 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000001914 filtration Methods 0.000 description 5
NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 5
239000000725 suspension Substances 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
238000001816 cooling Methods 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
150000004678 hydrides Chemical class 0.000 description 4
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
NETZHAKZCGBWSS-CEDHKZHLSA-N nalbuphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 NETZHAKZCGBWSS-CEDHKZHLSA-N 0.000 description 4
229960000805 nalbuphine Drugs 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
208000004756 Respiratory Insufficiency Diseases 0.000 description 3
206010038678 Respiratory depression Diseases 0.000 description 3
230000003042 antagnostic effect Effects 0.000 description 3
FLHFTXCMKFVKRP-UHFFFAOYSA-N bromomethylcyclobutane Chemical compound BrCC1CCC1 FLHFTXCMKFVKRP-UHFFFAOYSA-N 0.000 description 3
239000003610 charcoal Substances 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
206010052804 Drug tolerance Diseases 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 2
239000012965 benzophenone Substances 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 2
YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 2
238000004821 distillation Methods 0.000 description 2
LDDOSDVZPSGLFZ-UHFFFAOYSA-N ethyl cyclopropanecarboxylate Chemical compound CCOC(=O)C1CC1 LDDOSDVZPSGLFZ-UHFFFAOYSA-N 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
230000026781 habituation Effects 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
238000011835 investigation Methods 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
229960005118 oxymorphone Drugs 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
239000007787 solid Substances 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
WBMKMLWMIQUJDP-STHHAXOLSA-N (4R,4aS,7aR,12bS)-4a,9-dihydroxy-3-prop-2-ynyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one hydrochloride Chemical compound Cl.Oc1ccc2C[C@H]3N(CC#C)CC[C@@]45[C@@H](Oc1c24)C(=O)CC[C@@]35O WBMKMLWMIQUJDP-STHHAXOLSA-N 0.000 description 1
MISTZQJSHHTDCF-UHFFFAOYSA-N 1-(1-propoxyethoxy)propane Chemical compound CCCOC(C)OCCC MISTZQJSHHTDCF-UHFFFAOYSA-N 0.000 description 1
LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 1
LNNXOEHOXSYWLD-UHFFFAOYSA-N 1-bromobut-2-yne Chemical compound CC#CCBr LNNXOEHOXSYWLD-UHFFFAOYSA-N 0.000 description 1
CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 1
NBUHTTJGQKIBMR-UHFFFAOYSA-N 4,6-dimethylpyrimidin-5-amine Chemical compound CC1=NC=NC(C)=C1N NBUHTTJGQKIBMR-UHFFFAOYSA-N 0.000 description 1
HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
206010013654 Drug abuse Diseases 0.000 description 1
208000004547 Hallucinations Diseases 0.000 description 1
208000018526 Narcotic-Related disease Diseases 0.000 description 1
ONBWJWYUHXVEJS-ZTYRTETDSA-N Normorphine Chemical class C([C@@H](NCC1)[C@@H]2C=C[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 ONBWJWYUHXVEJS-ZTYRTETDSA-N 0.000 description 1
238000006036 Oppenauer oxidation reaction Methods 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
208000010513 Stupor Diseases 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
238000013019 agitation Methods 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
230000036626 alertness Effects 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
238000010171 animal model Methods 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
TXHIDIHEXDFONW-UHFFFAOYSA-N benzene;propan-2-one Chemical compound CC(C)=O.C1=CC=CC=C1 TXHIDIHEXDFONW-UHFFFAOYSA-N 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
230000035606 childbirth Effects 0.000 description 1
239000002026 chloroform extract Substances 0.000 description 1
KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
229940117975 chromium trioxide Drugs 0.000 description 1
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
WPOPOPFNZYPKAV-UHFFFAOYSA-N cyclobutylmethanol Chemical compound OCC1CCC1 WPOPOPFNZYPKAV-UHFFFAOYSA-N 0.000 description 1
RNIHFEJHABJCID-UHFFFAOYSA-N cyclobutylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CCC1 RNIHFEJHABJCID-UHFFFAOYSA-N 0.000 description 1
LZEPOJMTQYNFTR-UHFFFAOYSA-N cyclopropanecarbonyl cyclopropanecarboxylate Chemical compound C1CC1C(=O)OC(=O)C1CC1 LZEPOJMTQYNFTR-UHFFFAOYSA-N 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000010586 diagram Methods 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
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
230000003400 hallucinatory effect Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
229910010272 inorganic material Inorganic materials 0.000 description 1
239000011147 inorganic material Substances 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
239000007788 liquid Substances 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
239000000463 material Substances 0.000 description 1
229940051129 meperidine hydrochloride Drugs 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
229960004715 morphine sulfate Drugs 0.000 description 1
GRVOTVYEFDAHCL-RTSZDRIGSA-N morphine sulfate pentahydrate Chemical compound O.O.O.O.O.OS(O)(=O)=O.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O GRVOTVYEFDAHCL-RTSZDRIGSA-N 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
231100000957 no side effect Toxicity 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000011084 recovery Methods 0.000 description 1
239000006215 rectal suppository Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
239000002002 slurry Substances 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000005945 von Braun degradation reaction Methods 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

NO166137A 1966-01-19 1966-12-23 NO120368B (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US52170866A	1966-01-19	1966-01-19
US677727A US3393197A (en)	1966-01-19	1967-10-24	Nu-substituted-14-hydroxydihydronormorphines

Publications (1)

Publication Number	Publication Date
NO120368B true NO120368B (fr)	1970-10-12

Family

ID=27060549

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO166137A NO120368B (fr)	1966-01-19	1966-12-23

Country Status (13)

Country	Link
US (1)	US3393197A (fr)
AT (1)	AT292206B (fr)
CH (1)	CH493522A (fr)
DE (2)	DE1795707C3 (fr)
DK (1)	DK115631B (fr)
ES (1)	ES334942A1 (fr)
FR (1)	FR6112M (fr)
GB (1)	GB1119270A (fr)
IL (1)	IL26896A (fr)
LU (1)	LU52650A1 (fr)
NL (2)	NL165744C (fr)
NO (1)	NO120368B (fr)
SE (1)	SE329402B (fr)

Families Citing this family (57)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3476757A (en) *	1966-04-18	1969-11-04	Syntex Corp	Tetrahydropyranyl and tetrahydrofuranyl ethers of benzomorphans and morphanans
US4161597A (en) *	1976-12-20	1979-07-17	Research Corporation	N-alkyl-14-hydroxymorphinans and derivatives
GB1593191A (en) *	1977-03-23	1981-07-15	Reckitt & Colmann Prod Ltd	Derivatives of morphine
GB1587831A (en) *	1977-03-23	1981-04-08	Reckitt & Colmann Prod Ltd	Morphine derivatives
US4218454A (en) *	1977-07-08	1980-08-19	Sri International	N-αMethylcyclopropylmethyl derivatives of normorphine and noroodeine, and analgesic compositions and methods employing the normorphine derivatives
US4269843A (en) *	1978-05-24	1981-05-26	Sri International	N-Sec-alkyl analogs of norcodeine and normorphine and analgesic compositions and methods employing the normorphine derivatives
US4272541A (en) *	1978-06-02	1981-06-09	Miles Laboratories, Inc.	7,8 and 7-8 Substituted 4,5α-epoxymorphinan-6-one compounds, and methods of treating pain and drug dependence with them
US4236008A (en) *	1978-09-19	1980-11-25	E. I. Du Pont De Nemours And Company	Fluorination of precursors for fluorine analogs of hydrocodone and oxycodone
US4241065A (en) *	1979-07-02	1980-12-23	E. I. Du Pont De Nemours And Company	Fluoro analogs of hydrocodone and oxycodone useful as analgesics, narcotic antagonists or both
US4237140A (en) *	1979-05-18	1980-12-02	E. I. Du Pont De Nemours And Company	Analgesic mixture of nalbuphine and acetaminophen
US4282215A (en) *	1980-06-17	1981-08-04	E. I. Du Pont De Nemours And Company	Analgesic mixture of nalbuphine and acetylsalicylic acid, derivative or salt thereof
US4366159A (en) *	1981-09-08	1982-12-28	Michael Richard Magruder	Nalbuphine-narcotic analgesic composition and method of producing analgesia
US4407805A (en) *	1982-06-30	1983-10-04	E. I. Du Pont De Nemours And Company	Analgesic mixture of nalbuphine and zomepirac
US4404208A (en) *	1982-06-30	1983-09-13	E. I. Du Pont De Nemours And Company	Analgesic mixture of nalbuphine and tiflamizole
US4404209A (en) *	1982-06-30	1983-09-13	E. I. Du Pont De Nemours And Company	Analgesic mixture of nalbuphine and sulindac
US4407804A (en) *	1982-06-30	1983-10-04	E. I. Du Pont De Nemours And Company	Analgesic mixture of nalbuphine and indomethacin
US4404210A (en) *	1982-06-30	1983-09-13	E. I. Du Pont De Nemours And Company	Analgesic mixture of nalbuphine and ibuprofen
US4404211A (en) *	1982-06-30	1983-09-13	E. I. Du Pont De Nemours And Company	Analgesic mixture of nalbuphine and flurbiprofen
AU565634B2 (en) *	1982-06-30	1987-09-24	E.I. Du Pont De Nemours And Company	Synergistic compositions of nalbuphine and non-narcotic analgesic compounds
US4402962A (en) *	1982-06-30	1983-09-06	E. I. Du Pont De Nemours And Company	Analgesic mixture of nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole
US4477457A (en) *	1982-10-28	1984-10-16	E. I. Du Pont De Nemours And Company	Method for inducing anorexia using nalmetrene
US4478840A (en) *	1983-10-11	1984-10-23	E. I. Du Pont De Nemours And Company	Appetite suppressing compositions and methods
US4668685A (en) *	1984-07-05	1987-05-26	E.I. Du Pont De Nemours And Company	Substituted benzoate ester prodrug derivatives of 3-hydroxymorphinans, which are analgesics or narcotic antagonists
CA1280695C (fr) *	1985-04-29	1991-02-26	Benigno M. Sulit, Jr.	Compose de nalbuphine anesthesique local et analgesique et methode d'utilisation
DE4132159A1 (de) *	1991-09-27	1993-04-01	Boehringer Ingelheim Kg	14-hydroxy-n-(2-methoxyethyl)-7,8-dihydromorphin und -norisomorphin, verfahren zu deren herstellung und deren verwendung als arzneimittel
US5478577A (en) *	1993-11-23	1995-12-26	Euroceltique, S.A.	Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level
ES2127532T3 (es) *	1994-05-31	1999-04-16	Mallinckrodt Chemical Inc	Preparacion de nalbufina con niveles bajos del epimero beta.
US6348216B1 (en) *	1996-06-10	2002-02-19	Knoll Pharmaceutical Company	Ibuprofen and narcotic analgesic compositions
US6361794B1 (en)	1996-06-12	2002-03-26	Basf Corporation	Method of making ibuprofen and narcotic analgesic composition
US7585493B2 (en)	2001-05-24	2009-09-08	Alexza Pharmaceuticals, Inc.	Thin-film drug delivery article and method of use
US20030138508A1 (en) *	2001-12-18	2003-07-24	Novack Gary D.	Method for administering an analgesic
US7645442B2 (en)	2001-05-24	2010-01-12	Alexza Pharmaceuticals, Inc.	Rapid-heating drug delivery article and method of use
US7458374B2 (en)	2002-05-13	2008-12-02	Alexza Pharmaceuticals, Inc.	Method and apparatus for vaporizing a compound
US7090830B2 (en)	2001-05-24	2006-08-15	Alexza Pharmaceuticals, Inc.	Drug condensation aerosols and kits
US7766013B2 (en)	2001-06-05	2010-08-03	Alexza Pharmaceuticals, Inc.	Aerosol generating method and device
US20070122353A1 (en)	2001-05-24	2007-05-31	Hale Ron L	Drug condensation aerosols and kits
CA2446904A1 (fr)	2001-05-24	2003-04-03	Alexza Pharmaceuticals, Inc.	Administration d'esters medicamenteux par inhalation
US8329216B2 (en) *	2001-07-06	2012-12-11	Endo Pharmaceuticals Inc.	Oxymorphone controlled release formulations
KR20030048026A (ko) *	2001-07-06	2003-06-18	펜웨스트 파머슈티칼즈 컴파니	옥시모르폰의 서방형 제제
CN1610551A (zh)	2001-07-06	2005-04-27	恩德制药公司	用作止痛剂的6－羟基羟吗啡酮的肠胃外给药
AU2002337686B2 (en) *	2001-09-26	2008-05-15	Penwest Pharmaceuticals Company	Opioid formulations having reduced potential for abuse
US20040105818A1 (en)	2002-11-26	2004-06-03	Alexza Molecular Delivery Corporation	Diuretic aerosols and methods of making and using them
US7913688B2 (en)	2002-11-27	2011-03-29	Alexza Pharmaceuticals, Inc.	Inhalation device for producing a drug aerosol
EP1625333A1 (fr)	2003-05-21	2006-02-15	Alexza Pharmaceuticals, Inc.	Unite de chauffage autonome et unite de fourniture de medicament faisant appel a cette unite de chauffage
US7279579B2 (en) *	2003-06-04	2007-10-09	Alkermes, Inc.	Polymorphic forms of naltrexone
US7540286B2 (en)	2004-06-03	2009-06-02	Alexza Pharmaceuticals, Inc.	Multiple dose condensation aerosol devices and methods of forming condensation aerosols
EP2246086A3 (fr)	2004-08-12	2012-11-21	Alexza Pharmaceuticals, Inc.	Dispositif d'administration de médicament en aérosol comprenant une unité de chauffage allumée par percussion
US20070093517A1 (en) *	2005-10-24	2007-04-26	Gary Newton	Local anesthetic compositions
US20070212414A1 (en) *	2006-03-08	2007-09-13	Penwest Pharmaceuticals Co.	Ethanol-resistant sustained release formulations
KR101421747B1 (ko)	2006-04-21	2014-07-30	넥타르 테라퓨틱스	모르피논의 입체선택적 환원
EP2121088B1 (fr)	2007-03-09	2016-07-13	Alexza Pharmaceuticals, Inc.	Unité chauffante à utiliser dans un dispositif d'administration de médicament
WO2008118654A1 (fr) *	2007-03-23	2008-10-02	Mallinckrodt Inc.	Préparation améliorée d'oxymorphone à partir d'oripavine
WO2008130553A1 (fr) *	2007-04-16	2008-10-30	Mallinckrodt Inc.	Réduction d'opiacés innovante utilisant une réaction de transfert d'hydrogène catalytique
US20090124650A1 (en) *	2007-06-21	2009-05-14	Endo Pharmaceuticals, Inc.	Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instructions on Effects of Alcohol
ES2569655T3 (es) *	2007-12-17	2016-05-12	Mallinckrodt Llc	Procedimientos para la producción de compuestos de (+)-'nal' morfinano
WO2017046814A1 (fr) *	2015-09-14	2017-03-23	Rusan Pharma Limited	Procédé sûr et respectueux de l'environnement permettant de produire de la nalbuphine ou ses sels pharmaceutiquement acceptables
EP3746138B1 (fr)	2018-02-02	2025-12-10	Alexza Pharmaceuticals, Inc.	Dispositif aérosol à condensation électrique

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3320262A (en) *	1964-09-22	1967-05-16	Lewenstein	14 hydroxy morphine and codeine carboxymethyloximes

1966
- 1966-11-20 IL IL26896A patent/IL26896A/en unknown
- 1966-12-16 CH CH1803266A patent/CH493522A/de not_active IP Right Cessation
- 1966-12-16 GB GB56530/66A patent/GB1119270A/en not_active Expired
- 1966-12-19 DE DE1795707A patent/DE1795707C3/de not_active Expired
- 1966-12-19 DE DE1670616A patent/DE1670616C3/de not_active Expired
- 1966-12-20 LU LU52650D patent/LU52650A1/xx unknown
- 1966-12-22 SE SE17639/66A patent/SE329402B/xx unknown
- 1966-12-22 NL NL6618022.A patent/NL165744C/xx not_active IP Right Cessation
- 1966-12-23 NO NO166137A patent/NO120368B/no unknown
- 1966-12-23 AT AT1135867A patent/AT292206B/de not_active IP Right Cessation
- 1966-12-23 DK DK667766AA patent/DK115631B/da not_active IP Right Cessation
- 1966-12-26 ES ES334942A patent/ES334942A1/es not_active Expired
1967
- 1967-01-13 FR FR91097A patent/FR6112M/fr not_active Expired
- 1967-10-24 US US677727A patent/US3393197A/en not_active Expired - Lifetime
1978
- 1978-05-24 NL NL7805652A patent/NL7805652A/xx not_active Application Discontinuation

Also Published As

Publication number	Publication date
DE1670616C3 (de)	1978-06-29
NL7805652A (nl)	1978-09-29
ES334942A1 (es)	1968-03-01
US3393197A (en)	1968-07-16
DE1795707C3 (de)	1979-12-20
AT292206B (de)	1971-08-25
GB1119270A (en)	1968-07-10
NL165744B (nl)	1980-12-15
LU52650A1 (fr)	1967-02-20
DE1670616A1 (de)	1970-09-10
NL165744C (nl)	1981-05-15
DE1795707B2 (de)	1979-04-19
NL6618022A (fr)	1967-07-20
DK115631B (da)	1969-10-27
IL26896A (en)	1970-11-30
DE1795707A1 (de)	1973-10-11
DE1670616B2 (de)	1977-11-10
CH493522A (de)	1970-07-15
SE329402B (fr)	1970-10-12
FR6112M (fr)	1968-06-17

Publication	Publication Date	Title
NO120368B (fr)	1970-10-12
US3299072A (en)	1967-01-17	Thebaine derivatives
DE3212682A1 (de)	1982-10-21	Substituierte cyclobutane, verfahren zu ihrer herstellung und pharmazeutische zubereitungen, welche diese verbindungen enthalten
JPS60112792A (ja)	1985-06-19	６―デスオキシー６―メチレンナロキソンおよび６―デスオキシー６―メチレンナルトレキソンの製法
DE2265256A1 (de)	1977-01-27	Verfahren zur herstellung von analgetischen verbindungen
DE2539452A1 (de)	1976-03-18	1,3,4-trisubstituierte-4-arylpiperidine
JPS5835197B2 (ja)	1983-08-01	チンツウザイ
DE1518663A1 (de)	1969-12-18	Basisch substituierte Cycloalken-derivate und Verfahren zu ihrer Herstellung
US3513169A (en)	1970-05-19	5,9-diethyl benzomorphan derivatives
NO166137B (no)	1991-02-25	Fremgangsmaate for avsetning av et slitasjeresistent belegg paa et skjaereverktoey av et karbonholdig materiale.
US3828050A (en)	1974-08-06	3-alkoxy-14-acyloxydihydromorphinone derivatives
DE2159324C2 (de)	1984-06-14	Benzobicycloalkanamine,-aminoxide, Verfahren zu ihrer Herstellung und pharmazeutische Mittel, welche diese Verbindungen enthalten
DE2748466A1 (de)	1978-05-03	4a-aryloctahydro-1h-2-pyrindine
DE2311881A1 (de)	1973-09-20	Morphinanderivate
US3206480A (en)	1965-09-14	Dibenzofuranamines
DE1543388B1 (de)	1970-10-01	Basisch substituierte,tricyclische heterocyclische Verbindungen und deren pharmakologisch nicht giftige Salze sowie Verfahren zu ihrer Herstellung
US3936462A (en)	1976-02-03	1,2,3,4,5,6-Hexahydro-1-oxo or hydroxy-3-acyl-2,6-methano-3-benzazocines and corresponding 1-esters thereof
Burger et al.	1950	Amino Derivatives of 2, 2-Diphenylcyclohexanone. I1
DE1445606A1 (de)	1969-01-23	Benzoazacycloalkene
DE1545947A1 (de)	1969-12-11	Verfahren zur Herstellung von Iminodibenzyl-Derivaten
DE2015297A1 (de)	1970-10-15	Neue, in Stellung 5 substituierte 5H-Dibenzo eckige Klammer auf a,d eckige Klammer zu cycloheptene und Verfahren zu ihrer Herstellung
DE301870C (fr)
JPS5911577B2 (ja)	1984-03-16	２−ヒドロキシ−６，９−メタノ−１１−アミノ−５，６，７，８，９，１０−ヘキサヒドロ−ベンゾシクロオクテンのアミノ誘導体
DE2434015A1 (de)	1975-04-03	1-phenyl-6-azabicyclo eckige klammer auf 3,2,1 eckige klammer zu octanderivate, verfahren zu deren herstellung und dieselben enthaltendes mittel
CA1085834A (fr)	1980-09-16	Obtention d'hydrohalogenure de 8-halodihydrocodeinone