NO774155L - Nye fenylderivater. - Google Patents

Nye fenylderivater.

Info

Publication number: NO774155L
Authority: NO; Norway
Prior art keywords: compound; phenoxy; formula; methylmorphinan; lower alkyl
Prior art date: 1976-12-06

Application number

NO774155A

Other languages

English (en)

Norwegian (no)

Inventor

Ernest Mohacsi

Original Assignee

Hoffmann La Roche

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.)

1976-12-06

Filing date

1977-12-05

Publication date

1978-06-07

1977-06-29 Priority claimed from US05/811,233 external-priority patent/US4113729A/en

1977-12-05 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1978-06-07 Publication of NO774155L publication Critical patent/NO774155L/no

Links

CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 title 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 174
150000001875 compounds Chemical class 0.000 claims description 152
238000000034 method Methods 0.000 claims description 60
125000000217 alkyl group Chemical group 0.000 claims description 30
-1 3-phenoxy-N-substituted morphinan Chemical class 0.000 claims description 22
238000002360 preparation method Methods 0.000 claims description 21
229960004126 codeine Drugs 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 16
229910052739 hydrogen Inorganic materials 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
150000002431 hydrogen Chemical class 0.000 claims description 10
229910052740 iodine Inorganic materials 0.000 claims description 10
238000002156 mixing Methods 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
PWLXGNOVURURNQ-MDNUFGMLSA-N (-)-3-phenoxy-n-methylmorphinan Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1C)[H])C2=CC=C3OC1=CC=CC=C1 PWLXGNOVURURNQ-MDNUFGMLSA-N 0.000 claims description 6
125000001072 heteroaryl group Chemical group 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
230000000202 analgesic effect Effects 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 5
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
GWYZMUPEPNNPDO-GGBSJPMNSA-N (-)-3-phenoxy-n-cyclopropylcarbonylmorphinan Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1C(=O)C1CC1)[H])C2=CC=C3OC1=CC=CC=C1 GWYZMUPEPNNPDO-GGBSJPMNSA-N 0.000 claims description 3
HZJQJGYYKQYCDE-GNSPLJBXSA-N (-)-3-phenoxy-n-phenethylmorphinan Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1CCC=1C=CC=CC=1)[H])C2=CC=C3OC1=CC=CC=C1 HZJQJGYYKQYCDE-GNSPLJBXSA-N 0.000 claims description 3
XYYFHBGOYHWPFV-UHFFFAOYSA-N 2-methyl-1-[(4-phenoxyphenyl)methyl]-3,4,5,6,7,8-hexahydro-1h-isoquinoline Chemical compound CN1CCC(CCCC2)=C2C1CC(C=C1)=CC=C1OC1=CC=CC=C1 XYYFHBGOYHWPFV-UHFFFAOYSA-N 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical compound C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 claims description 3
229940051807 opiod analgesics morphinan derivative Drugs 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
238000012546 transfer Methods 0.000 claims description 3
239000011701 zinc Substances 0.000 claims description 3
229910052725 zinc Inorganic materials 0.000 claims description 3
XHCNZHWSZVMLAZ-KJYTXNCISA-N (-)-3-phenoxy-n-[2-(2-furyl)ethyl]morphinan Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1CCC=1OC=CC=1)[H])C2=CC=C3OC1=CC=CC=C1 XHCNZHWSZVMLAZ-KJYTXNCISA-N 0.000 claims description 2
MJCDPGDYLGVXLX-BGWNEDDSSA-N (-)-3-phenoxy-n-trichlorocarbethoxymorphinan Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1C(=O)OCC(Cl)(Cl)Cl)[H])C2=CC=C3OC1=CC=CC=C1 MJCDPGDYLGVXLX-BGWNEDDSSA-N 0.000 claims description 2
AXPRHBMSSFWEHZ-SKBVVQJISA-N (1R,9R,10R)-17-(cyclopropylmethyl)-4-phenoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1CC1CC1)[H])C2=CC=C3OC1=CC=CC=C1 AXPRHBMSSFWEHZ-SKBVVQJISA-N 0.000 claims description 2
239000012876 carrier material Substances 0.000 claims description 2
239000007788 liquid Substances 0.000 claims description 2
239000007787 solid Substances 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 7
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
239000004480 active ingredient Substances 0.000 claims 1
239000000969 carrier Substances 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
231100000252 nontoxic Toxicity 0.000 claims 1
230000003000 nontoxic effect Effects 0.000 claims 1
230000001225 therapeutic effect Effects 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 156
239000000243 solution Substances 0.000 description 72
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 61
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 52
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 47
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 42
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 40
239000011541 reaction mixture Substances 0.000 description 36
238000006243 chemical reaction Methods 0.000 description 35
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 33
238000002844 melting Methods 0.000 description 32
230000008018 melting Effects 0.000 description 32
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
239000002904 solvent Substances 0.000 description 29
238000010992 reflux Methods 0.000 description 27
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
238000009835 boiling Methods 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
239000002585 base Substances 0.000 description 21
229910052757 nitrogen Inorganic materials 0.000 description 21
239000000706 filtrate Substances 0.000 description 20
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
229910000027 potassium carbonate Inorganic materials 0.000 description 17
238000003756 stirring Methods 0.000 description 17
235000019439 ethyl acetate Nutrition 0.000 description 16
235000011181 potassium carbonates Nutrition 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
239000000725 suspension Substances 0.000 description 15
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
229910052802 copper Inorganic materials 0.000 description 14
239000010949 copper Substances 0.000 description 14
239000000203 mixture Substances 0.000 description 14
239000000047 product Substances 0.000 description 13
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 11
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 description 10
239000000908 ammonium hydroxide Substances 0.000 description 10
235000006408 oxalic acid Nutrition 0.000 description 9
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
239000012280 lithium aluminium hydride Substances 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound 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 description 8
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
238000002425 crystallisation Methods 0.000 description 7
230000008025 crystallization Effects 0.000 description 7
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
238000013459 approach Methods 0.000 description 6
239000002775 capsule Substances 0.000 description 6
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
239000002798 polar solvent Substances 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 5
230000020335 dealkylation Effects 0.000 description 5
238000006900 dealkylation reaction Methods 0.000 description 5
238000005661 deetherification reaction Methods 0.000 description 5
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
229910000147 aluminium phosphate Inorganic materials 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
230000008485 antagonism Effects 0.000 description 4
QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
229960001270 d- tartaric acid Drugs 0.000 description 4
150000007529 inorganic bases Chemical class 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
229960005181 morphine Drugs 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
229940095064 tartrate Drugs 0.000 description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 4
XNJVYGJIDQNXTL-KSEOMHKRSA-N (1R,9R,10R)-4-phenoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1)[H])C2=CC=C3OC1=CC=CC=C1 XNJVYGJIDQNXTL-KSEOMHKRSA-N 0.000 description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
150000008044 alkali metal hydroxides Chemical class 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
150000004945 aromatic hydrocarbons Chemical class 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
ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
230000000694 effects Effects 0.000 description 3
OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 3
125000004356 hydroxy functional group Chemical group O* 0.000 description 3
229910052500 inorganic mineral Inorganic materials 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
150000003512 tertiary amines Chemical class 0.000 description 3
238000012360 testing method Methods 0.000 description 3
POLBUGDCWRJCEO-XOGZZPMPSA-N (-)-3-phenoxy-n-cyclobutylmethylmorphinan hydrochloride Chemical compound Cl.C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1CC1CCC1)[H])C2=CC=C3OC1=CC=CC=C1 POLBUGDCWRJCEO-XOGZZPMPSA-N 0.000 description 2
OKCBBODMVLQPKM-LIXABZRUSA-N (1R,9R,10R)-17-(cyclopropylmethyl)-4-phenoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene hydrochloride Chemical compound Cl.C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1CC1CC1)[H])C2=CC=C3OC1=CC=CC=C1 OKCBBODMVLQPKM-LIXABZRUSA-N 0.000 description 2
MWHCGABAVDOYQS-DKRHUIDYSA-N 1-[(1R,9R,10R)-4-phenoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-17-yl]-2-thiophen-2-ylethanone Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1C(=O)CC=1SC=CC=1)[H])C2=CC=C3OC1=CC=CC=C1 MWHCGABAVDOYQS-DKRHUIDYSA-N 0.000 description 2
NMFJSADPLJZVNC-UHFFFAOYSA-N 4-[(2-methyl-3,4,5,6,7,8-hexahydro-1h-isoquinolin-1-yl)methyl]phenol Chemical compound CN1CCC(CCCC2)=C2C1CC1=CC=C(O)C=C1 NMFJSADPLJZVNC-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
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
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
208000002193 Pain Diseases 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
239000013543 active substance Substances 0.000 description 2
229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
150000008041 alkali metal carbonates Chemical class 0.000 description 2
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
230000036592 analgesia Effects 0.000 description 2
229940035676 analgesics Drugs 0.000 description 2
239000000730 antalgic agent Substances 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
KHIVJMCELJPZHP-VXQMPNGUSA-N cyclobutyl-[(1R,9R,10R)-4-phenoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-17-yl]methanone Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1C(=O)C1CCC1)[H])C2=CC=C3OC1=CC=CC=C1 KHIVJMCELJPZHP-VXQMPNGUSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000008187 granular material Substances 0.000 description 2
ZQBFAOFFOQMSGJ-UHFFFAOYSA-N hexafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1F ZQBFAOFFOQMSGJ-UHFFFAOYSA-N 0.000 description 2
QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 2
150000002430 hydrocarbons Chemical group 0.000 description 2
229910000042 hydrogen bromide Inorganic materials 0.000 description 2
FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
239000011707 mineral Substances 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
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235000017550 sodium carbonate Nutrition 0.000 description 2
229910001220 stainless steel Inorganic materials 0.000 description 2
239000010935 stainless steel Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
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HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
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SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
230000037396 body weight Effects 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
MXEOIGQNIHTYGL-TYMHPWAKSA-N chembl2062278 Chemical compound OC(=O)C(O)C(O)C(O)=O.C([C@@H]1[C@@H]2CCCC[C@@]2(C2=C3)CCN1C)C2=CC=C3OC1=CC=CC=C1 MXEOIGQNIHTYGL-TYMHPWAKSA-N 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
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239000002026 chloroform extract Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
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239000003245 coal Substances 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
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229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
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239000013078 crystal Substances 0.000 description 1
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238000004821 distillation Methods 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
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239000003814 drug Substances 0.000 description 1
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238000010828 elution Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
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235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
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239000013067 intermediate product Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000004571 lime Substances 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
239000003887 narcotic antagonist Substances 0.000 description 1
230000003533 narcotic effect Effects 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
RLXDCJUIXHSXQD-UHFFFAOYSA-N oxalic acid;hydrate Chemical compound O.OC(=O)C(O)=O.OC(=O)C(O)=O RLXDCJUIXHSXQD-UHFFFAOYSA-N 0.000 description 1
TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
239000003973 paint Substances 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
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229960004889 salicylic acid Drugs 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
229960001367 tartaric acid Drugs 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
- C07D221/28—Morphinans

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pain & Pain Management (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biomedical Technology (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Other In-Based Heterocyclic Compounds (AREA)

NO774155A 1976-12-06 1977-12-05 Nye fenylderivater. NO774155L (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US74802276A	1976-12-06	1976-12-06
US05/811,233 US4113729A (en)	1976-12-06	1977-06-29	3-Phenoxymorphinans and derivatives thereof

Publications (1)

Publication Number	Publication Date
NO774155L true NO774155L (no)	1978-06-07

Family

ID=27114858

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO774155A NO774155L (no)	1976-12-06	1977-12-05	Nye fenylderivater.

Country Status (22)

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JP (1)	JPS5392776A (it)
AR (1)	AR219510A1 (it)
AT (1)	AT364826B (it)
AU (1)	AU514827B2 (it)
CA (1)	CA1088935A (it)
DE (1)	DE2754062A1 (it)
DK (1)	DK540977A (it)
ES (3)	ES464751A1 (it)
FI (1)	FI773636A (it)
FR (1)	FR2372808A1 (it)
GB (1)	GB1589792A (it)
HU (1)	HU177640B (it)
IE (1)	IE46003B1 (it)
IL (1)	IL53532A (it)
IT (1)	IT1143727B (it)
LU (1)	LU78638A1 (it)
MC (1)	MC1172A1 (it)
NL (1)	NL7713432A (it)
NO (1)	NO774155L (it)
NZ (1)	NZ185860A (it)
PT (1)	PT67363B (it)
SE (1)	SE7713779L (it)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4247697A (en) *	1979-09-10	1981-01-27	Hoffmann-La Roche Inc.	3-Phenoxy morphinans and their derivatives
TW264473B (it) *	1993-01-06	1995-12-01	Hoffmann La Roche

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CH543514A (de) *	1967-08-25	1973-10-31	Hoffmann La Roche	Verfahren zur Herstellung von Morphinanderivaten
JPS493961B1 (it) *	1969-06-24	1974-01-29

1977
- 1977-11-30 FI FI773636A patent/FI773636A/fi not_active Application Discontinuation
- 1977-12-05 GB GB50495/77A patent/GB1589792A/en not_active Expired
- 1977-12-05 NL NL7713432A patent/NL7713432A/xx not_active Application Discontinuation
- 1977-12-05 NO NO774155A patent/NO774155L/no unknown
- 1977-12-05 DK DK540977A patent/DK540977A/da unknown
- 1977-12-05 PT PT67363A patent/PT67363B/pt unknown
- 1977-12-05 ES ES464751A patent/ES464751A1/es not_active Expired
- 1977-12-05 SE SE7713779A patent/SE7713779L/xx not_active Application Discontinuation
- 1977-12-05 IL IL53532A patent/IL53532A/xx unknown
- 1977-12-05 DE DE19772754062 patent/DE2754062A1/de not_active Withdrawn
- 1977-12-05 CA CA292,433A patent/CA1088935A/en not_active Expired
- 1977-12-05 JP JP14520377A patent/JPS5392776A/ja active Pending
- 1977-12-05 AT AT0869277A patent/AT364826B/de not_active IP Right Cessation
- 1977-12-05 MC MC771272A patent/MC1172A1/xx unknown
- 1977-12-05 HU HU77HO2029A patent/HU177640B/hu unknown
- 1977-12-05 LU LU7778638A patent/LU78638A1/xx unknown
- 1977-12-05 IE IE2468/77A patent/IE46003B1/en unknown
- 1977-12-05 NZ NZ185860A patent/NZ185860A/xx unknown
- 1977-12-06 FR FR7736745A patent/FR2372808A1/fr active Granted
- 1977-12-06 AU AU31264/77A patent/AU514827B2/en not_active Expired
- 1977-12-06 IT IT30510/77A patent/IT1143727B/it active
- 1977-12-06 AR AR270265A patent/AR219510A1/es active
1978
- 1978-08-16 ES ES472573A patent/ES472573A1/es not_active Expired
- 1978-08-16 ES ES472572A patent/ES472572A1/es not_active Expired

Also Published As

Publication number	Publication date
AU514827B2 (en)	1981-02-26
FI773636A (fi)	1978-06-07
AR219510A1 (es)	1980-08-29
IL53532A0 (en)	1978-03-10
IE46003B1 (en)	1983-01-26
NZ185860A (en)	1980-10-24
HU177640B (en)	1981-11-28
FR2372808B1 (it)	1981-07-10
DK540977A (da)	1978-06-07
ES464751A1 (es)	1978-12-16
JPS5392776A (en)	1978-08-15
SE7713779L (sv)	1978-06-07
AT364826B (de)	1981-11-25
IT1143727B (it)	1986-10-22
GB1589792A (en)	1981-05-20
FR2372808A1 (fr)	1978-06-30
AU3126477A (en)	1979-06-14
ES472572A1 (es)	1979-02-16
NL7713432A (nl)	1978-06-08
IL53532A (en)	1981-09-13
PT67363A (en)	1978-01-01
ATA869277A (de)	1981-04-15
PT67363B (en)	1979-12-17
ES472573A1 (es)	1979-02-16
IE46003L (en)	1978-06-06
DE2754062A1 (de)	1978-06-08
LU78638A1 (it)	1979-02-02
CA1088935A (en)	1980-11-04
MC1172A1 (fr)	1978-09-25

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JPH0153671B2 (it)	1989-11-15
JPS6289679A (ja)	1987-04-24	ピペリジン誘導体
US3714149A (en)	1973-01-30	Pyridobenzodiazepinones
JPH0251897B2 (it)	1990-11-08
JPH06502871A (ja)	1994-03-31	新規のβ−カルボリン誘導体、その製造および医薬品としての使用
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CA1180335A (en)	1985-01-02	3-amino-1-aryl-2-pyrazoline compounds
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NO762085L (it)	1976-12-28
EP0001585B1 (de)	1981-07-22	Piperazino-pyrrolobenzodiazepine, Verfahren zu ihrer Herstellung sowie pharmazeutische Präparate enthaltend diese Verbindungen
USRE30452E (en)	1980-12-16	3-Phenoxymorphinans and derivatives thereof
JPH0433795B2 (it)	1992-06-04
US3420841A (en)	1969-01-07	1,3-di-(4-pyridyl)propane derivatives