CA1100136A - 4a-aryl octahydro-1h-2-pyrindines - Google Patents
4a-aryl octahydro-1h-2-pyrindinesInfo
- Publication number
- CA1100136A CA1100136A CA289,687A CA289687A CA1100136A CA 1100136 A CA1100136 A CA 1100136A CA 289687 A CA289687 A CA 289687A CA 1100136 A CA1100136 A CA 1100136A
- Authority
- CA
- Canada
- Prior art keywords
- octahydro
- pyrindine
- hydroxyphenyl
- phenyl
- compound
- 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.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 68
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 13
- 239000002168 alkylating agent Substances 0.000 claims abstract description 12
- 229940100198 alkylating agent Drugs 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 49
- 239000002253 acid Substances 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 13
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 229960000583 acetic acid Drugs 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 231100000252 nontoxic Toxicity 0.000 claims description 6
- 230000003000 nontoxic effect Effects 0.000 claims description 6
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
- NNTYFRJCGLTEMW-UHFFFAOYSA-N 4a-(3-methoxyphenyl)-1,2,3,4,5,6,7,7a-octahydrocyclopenta[c]pyridine Chemical compound COC1=CC=CC(C23C(CCC2)CNCC3)=C1 NNTYFRJCGLTEMW-UHFFFAOYSA-N 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 239000012362 glacial acetic acid Substances 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- UHMCIKFAUSFZLW-UHFFFAOYSA-N 3-(1,2,3,4,5,6,7,7a-octahydrocyclopenta[c]pyridin-4a-yl)phenol Chemical compound OC1=CC=CC(C23C(CCC2)CNCC3)=C1 UHMCIKFAUSFZLW-UHFFFAOYSA-N 0.000 claims description 4
- HTEVNWBCKRJEST-UHFFFAOYSA-N 4a-(3-methoxyphenyl)-2-pentyl-3,4,5,6,7,7a-hexahydro-1h-cyclopenta[c]pyridine Chemical compound C1CCC2CN(CCCCC)CCC21C1=CC=CC(OC)=C1 HTEVNWBCKRJEST-UHFFFAOYSA-N 0.000 claims description 4
- HFEHLDPGIKPNKL-UHFFFAOYSA-N allyl iodide Chemical compound ICC=C HFEHLDPGIKPNKL-UHFFFAOYSA-N 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 claims description 3
- WHHZDVZHTFWSRD-UHFFFAOYSA-N 3-[2-(cyclopropylmethyl)-3,4,5,6,7,7a-hexahydro-1H-cyclopenta[c]pyridin-4a-yl]phenol Chemical compound OC=1C=C(C=CC1)C12CCN(CC2CCC1)CC1CC1 WHHZDVZHTFWSRD-UHFFFAOYSA-N 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- VOHILFSOWRNVJJ-UHFFFAOYSA-N 2-(bromomethyl)oxolane Chemical compound BrCC1CCCO1 VOHILFSOWRNVJJ-UHFFFAOYSA-N 0.000 claims description 2
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 13
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 6
- 230000002152 alkylating effect Effects 0.000 claims 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 3
- VUKNOJLWFRGGOF-UHFFFAOYSA-N 4a-(3-methoxyphenyl)-2-propyl-3,4,5,6,7,7a-hexahydro-1h-cyclopenta[c]pyridine Chemical compound C1CCC2CN(CCC)CCC21C1=CC=CC(OC)=C1 VUKNOJLWFRGGOF-UHFFFAOYSA-N 0.000 claims 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- XNFIZOUXSFKBHL-UHFFFAOYSA-N 3-(2-pentyl-3,4,5,6,7,7a-hexahydro-1h-cyclopenta[c]pyridin-4a-yl)phenol Chemical compound C1CCC2CN(CCCCC)CCC21C1=CC=CC(O)=C1 XNFIZOUXSFKBHL-UHFFFAOYSA-N 0.000 claims 2
- QOZKQIRLIRKQIE-UHFFFAOYSA-N 3-(2-prop-2-enyl-3,4,5,6,7,7a-hexahydro-1h-cyclopenta[c]pyridin-4a-yl)phenol Chemical compound OC1=CC=CC(C23C(CCC2)CN(CC=C)CC3)=C1 QOZKQIRLIRKQIE-UHFFFAOYSA-N 0.000 claims 2
- UTOZTQIBZHHHNJ-UHFFFAOYSA-N 3-(2-propyl-3,4,5,6,7,7a-hexahydro-1h-cyclopenta[c]pyridin-4a-yl)phenol Chemical compound C1CCC2CN(CCC)CCC21C1=CC=CC(O)=C1 UTOZTQIBZHHHNJ-UHFFFAOYSA-N 0.000 claims 2
- YZWKKMVJZFACSU-UHFFFAOYSA-N 1-bromopentane Chemical compound CCCCCBr YZWKKMVJZFACSU-UHFFFAOYSA-N 0.000 claims 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims 1
- 239000000730 antalgic agent Substances 0.000 abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 95
- 239000000243 solution Substances 0.000 description 58
- 239000011541 reaction mixture Substances 0.000 description 47
- FGFBEHFJSQBISW-UHFFFAOYSA-N 1h-cyclopenta[b]pyridine Chemical class C1=CNC2=CC=CC2=C1 FGFBEHFJSQBISW-UHFFFAOYSA-N 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 44
- 239000002904 solvent Substances 0.000 description 35
- 239000003921 oil Substances 0.000 description 34
- 235000019198 oils Nutrition 0.000 description 34
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- 239000000047 product Substances 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 238000004458 analytical method Methods 0.000 description 24
- 238000001704 evaporation Methods 0.000 description 23
- 230000008020 evaporation Effects 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 230000000202 analgesic effect Effects 0.000 description 10
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 235000011121 sodium hydroxide Nutrition 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000003638 chemical reducing agent Substances 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 150000004880 oxines Chemical class 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 150000003141 primary amines Chemical class 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- IVAATAQAFOAALG-UHFFFAOYSA-N 2h-cyclopenta[c]pyridine Chemical class C1=CNC=C2C=CC=C21 IVAATAQAFOAALG-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229940035676 analgesics Drugs 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 241000124008 Mammalia Species 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 230000036592 analgesia Effects 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 229940093956 potassium carbonate Drugs 0.000 description 5
- 235000011181 potassium carbonates Nutrition 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 229960001407 sodium bicarbonate Drugs 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- PGJZFAPVZDXDNA-UHFFFAOYSA-N 4a-phenyl-1,2,3,4,5,6,7,7a-octahydrocyclopenta[c]pyridine Chemical compound C1CCC2CNCCC21C1=CC=CC=C1 PGJZFAPVZDXDNA-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 230000010933 acylation Effects 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 230000036461 convulsion Effects 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- KPXSPHQLZBMRLW-UHFFFAOYSA-N 2,3,4,4a,5,6,7,7a-octahydro-1h-cyclopenta[c]pyridine Chemical class C1CNCC2CCCC21 KPXSPHQLZBMRLW-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000010779 crude oil Substances 0.000 description 3
- 238000006264 debenzylation reaction Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 3
- 229960004127 naloxone Drugs 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- FRVZWIGAQXKWER-UHFFFAOYSA-N 2-benzyl-4a-(3-methoxyphenyl)-5,6,7,7a-tetrahydro-4h-cyclopenta[c]pyridine-1,3-dione Chemical compound COC1=CC=CC(C23C(CCC2)C(=O)N(CC=2C=CC=CC=2)C(=O)C3)=C1 FRVZWIGAQXKWER-UHFFFAOYSA-N 0.000 description 2
- DTGIQJKGEJIAAL-UHFFFAOYSA-N 2-ethyl-4a-phenyl-3,4,5,6,7,7a-hexahydro-1h-cyclopenta[c]pyridine Chemical compound C1CCC2CN(CC)CCC21C1=CC=CC=C1 DTGIQJKGEJIAAL-UHFFFAOYSA-N 0.000 description 2
- BPPPUFSZQDCMEE-UHFFFAOYSA-N 2-oxocyclohexane-1-carbaldehyde Chemical class O=CC1CCCCC1=O BPPPUFSZQDCMEE-UHFFFAOYSA-N 0.000 description 2
- DRLVMOAWNVOSPE-UHFFFAOYSA-N 2-phenylcyclohexan-1-one Chemical compound O=C1CCCCC1C1=CC=CC=C1 DRLVMOAWNVOSPE-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- LPMQLTPCZIWTLF-UHFFFAOYSA-N 3-[2-(2-phenylethyl)-3,4,5,6,7,7a-hexahydro-1h-cyclopenta[c]pyridin-4a-yl]phenol Chemical compound OC1=CC=CC(C23C(CCC2)CN(CCC=2C=CC=CC=2)CC3)=C1 LPMQLTPCZIWTLF-UHFFFAOYSA-N 0.000 description 2
- 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 2
- DAUWHPNJBHKVJK-UHFFFAOYSA-N 4a-(3-methoxyphenyl)-2-methyl-3,4,5,6,7,7a-hexahydro-1h-cyclopenta[c]pyridine Chemical compound COC1=CC=CC(C23C(CCC2)CN(C)CC3)=C1 DAUWHPNJBHKVJK-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 206010012335 Dependence Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 239000012670 alkaline solution Substances 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- NGPGDYLVALNKEG-UHFFFAOYSA-N azanium;azane;2,3,4-trihydroxy-4-oxobutanoate Chemical compound [NH4+].[NH4+].[O-]C(=O)C(O)C(O)C([O-])=O NGPGDYLVALNKEG-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- AQIHMSVIAGNIDM-UHFFFAOYSA-N benzoyl bromide Chemical compound BrC(=O)C1=CC=CC=C1 AQIHMSVIAGNIDM-UHFFFAOYSA-N 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- CHIWXYAWZYPFJS-UHFFFAOYSA-N bromomethoxybenzene Chemical compound BrCOC1=CC=CC=C1 CHIWXYAWZYPFJS-UHFFFAOYSA-N 0.000 description 1
- 125000003865 brosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)S(*)(=O)=O 0.000 description 1
- KKBWAGPOKIAPAW-UHFFFAOYSA-N butoxyalumane Chemical compound CCCCO[AlH2] KKBWAGPOKIAPAW-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- ZVTQWXCKQTUVPY-UHFFFAOYSA-N chloromethylcyclopropane Chemical compound ClCC1CC1 ZVTQWXCKQTUVPY-UHFFFAOYSA-N 0.000 description 1
- WTEVQBCEXWBHNA-JXMROGBWSA-N citral A Natural products CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- AVLJDNPAYGPMMJ-UHFFFAOYSA-N cyclobutanecarbonyl bromide Chemical compound BrC(=O)C1CCC1 AVLJDNPAYGPMMJ-UHFFFAOYSA-N 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- IABZFPLSDXDLRS-UHFFFAOYSA-N cyclohexylmethyl methanesulfonate Chemical compound CS(=O)(=O)OCC1CCCCC1 IABZFPLSDXDLRS-UHFFFAOYSA-N 0.000 description 1
- CGFCQGODEOUVFT-UHFFFAOYSA-N cyclopenta[b]pyran-2,3-dione Chemical class O=C1C(=O)OC2=CC=CC2=C1 CGFCQGODEOUVFT-UHFFFAOYSA-N 0.000 description 1
- QFWIZBDAWJSJOT-UHFFFAOYSA-N cyclopenta[c]pyridine-1,3-dione Chemical compound O=C1NC(C=C2C=CC=C12)=O QFWIZBDAWJSJOT-UHFFFAOYSA-N 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 1
- 229960004193 dextropropoxyphene Drugs 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- ZEUNFSXJLTXSBS-UHFFFAOYSA-N ethyl 2-[1-(3-hydroxyphenyl)-2-oxocyclohexyl]acetate Chemical compound C=1C=CC(O)=CC=1C1(CC(=O)OCC)CCCCC1=O ZEUNFSXJLTXSBS-UHFFFAOYSA-N 0.000 description 1
- XIAYIHJKGNBZON-UHFFFAOYSA-N ethyl 2-[1-(3-methoxyphenyl)-2-oxocyclohexyl]acetate Chemical compound C=1C=CC(OC)=CC=1C1(CC(=O)OCC)CCCCC1=O XIAYIHJKGNBZON-UHFFFAOYSA-N 0.000 description 1
- NBGQWTYYPGXUBM-UHFFFAOYSA-N ethyl 2-[3-formyl-1-(3-methoxyphenyl)-2-oxocyclohexyl]acetate Chemical compound C=1C=CC(OC)=CC=1C1(CC(=O)OCC)CCCC(C=O)C1=O NBGQWTYYPGXUBM-UHFFFAOYSA-N 0.000 description 1
- IMMGIMKNXZXXLY-UHFFFAOYSA-N ethyl 3-diazo-6-methyl-2-oxo-1-phenylcyclohexane-1-carboxylate Chemical compound C1(=CC=CC=C1)C1(C(C(CCC1C)=[N+]=[N-])=O)C(=O)OCC IMMGIMKNXZXXLY-UHFFFAOYSA-N 0.000 description 1
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- GFAUNYMRSKVDJL-UHFFFAOYSA-N formyl chloride Chemical compound ClC=O GFAUNYMRSKVDJL-UHFFFAOYSA-N 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- PIXBVQFCTGBRHV-UHFFFAOYSA-N hex-4-enoyl chloride Chemical compound CC=CCCC(Cl)=O PIXBVQFCTGBRHV-UHFFFAOYSA-N 0.000 description 1
- PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- ATADHKWKHYVBTJ-UHFFFAOYSA-N hydron;4-[1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol;chloride Chemical compound Cl.CNCC(O)C1=CC=C(O)C(O)=C1 ATADHKWKHYVBTJ-UHFFFAOYSA-N 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002537 isoquinolines Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- ANAFTYVSHCSQPP-UHFFFAOYSA-N lithium;trimethoxyalumane Chemical compound [Li].CO[Al](OC)OC ANAFTYVSHCSQPP-UHFFFAOYSA-N 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
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- BWLHABBEJLLEBV-UHFFFAOYSA-N methyl 2-(2-ethoxy-2-oxoethyl)-2-(3-methoxyphenyl)cyclopentane-1-carboxylate Chemical compound C=1C=CC(OC)=CC=1C1(CC(=O)OCC)CCCC1C(=O)OC BWLHABBEJLLEBV-UHFFFAOYSA-N 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 230000000945 opiatelike Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- XGISHOFUAFNYQF-UHFFFAOYSA-N pentanoyl chloride Chemical compound CCCCC(Cl)=O XGISHOFUAFNYQF-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 235000007686 potassium Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000007157 ring contraction reaction Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 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
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229940083608 sodium hydroxide Drugs 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- NDLIRBZKZSDGSO-UHFFFAOYSA-N tosyl azide Chemical compound CC1=CC=C(S(=O)(=O)[N-][N+]#N)C=C1 NDLIRBZKZSDGSO-UHFFFAOYSA-N 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 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
- 229940086542 triethylamine Drugs 0.000 description 1
- JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
- C07D221/04—Ortho- or peri-condensed ring systems
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/757—Unsaturated compounds containing a keto groups being part of a ring containing —CHO groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/94—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pain & Pain Management (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000364856A CA1119175A (en) | 1976-11-02 | 1980-11-17 | 4a-aryl octahydro-1h-2-pyrindines |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73795876A | 1976-11-02 | 1976-11-02 | |
| US737,958 | 1976-11-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1100136A true CA1100136A (en) | 1981-04-28 |
Family
ID=24965981
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA289,687A Expired CA1100136A (en) | 1976-11-02 | 1977-10-27 | 4a-aryl octahydro-1h-2-pyrindines |
Country Status (26)
| Country | Link |
|---|---|
| JP (1) | JPS5356669A (cs) |
| AR (1) | AR223454A1 (cs) |
| AT (1) | ATA782177A (cs) |
| AU (1) | AU513679B2 (cs) |
| BE (1) | BE860314A (cs) |
| CA (1) | CA1100136A (cs) |
| CS (1) | CS211380B2 (cs) |
| DD (1) | DD133795A5 (cs) |
| DE (1) | DE2748466A1 (cs) |
| DK (1) | DK485277A (cs) |
| ES (3) | ES463783A1 (cs) |
| FR (1) | FR2369267A1 (cs) |
| GB (1) | GB1590155A (cs) |
| GR (1) | GR70053B (cs) |
| HU (1) | HU176231B (cs) |
| IE (1) | IE45901B1 (cs) |
| IL (1) | IL53236A0 (cs) |
| NL (1) | NL7712053A (cs) |
| NZ (1) | NZ185539A (cs) |
| PH (1) | PH12590A (cs) |
| PL (3) | PL108610B1 (cs) |
| PT (1) | PT67194B (cs) |
| RO (3) | RO72900A (cs) |
| SE (3) | SE7712218L (cs) |
| SU (3) | SU812174A3 (cs) |
| ZA (1) | ZA776497B (cs) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ189230A (en) * | 1977-12-27 | 1981-05-15 | Lilly Co Eli | Trans-4a-aryl-2-substituted-octahydro-1h-2-pyrindines |
| US4236009A (en) * | 1979-06-21 | 1980-11-25 | Eli Lilly And Company | Method of preparing 4A-arylhexahydro-1H-2-pyrindines and 4A-aryloctahydroisoquinolines |
| US4277608A (en) * | 1979-06-21 | 1981-07-07 | Eli Lilly And Company | Method of preparing 4a-arylhexahydro-1H-2-pyrindines and 4a-aryloctahydroisoquinolines |
| ZA9510829B (en) * | 1994-12-23 | 1996-07-03 | Smithkline Beecham Corp | 3,3-(disubstituted)cyclohexan-1-one monomers and related compounds |
| HUE028983T2 (en) | 2010-05-06 | 2017-01-30 | Vertex Pharma | Heterocyclic chromene-spirocyclic piperidine amides as ion channel modulators |
| HRP20160382T8 (hr) | 2011-02-02 | 2016-10-21 | Vertex Pharmaceuticals Incorporated | Pirolopirazin-spirociklični piperidin amidi kao modulatori ionskih kanala |
| CN103443105A (zh) | 2011-02-18 | 2013-12-11 | 沃泰克斯药物股份有限公司 | 作为离子通道调节剂的苯并二氢吡喃-螺环哌啶酰胺 |
| MX347982B (es) | 2011-03-14 | 2017-05-22 | Vertex Pharma | Morfolina-piperidina espirociclica-amidas como moduladores de canales ionicos. |
-
1977
- 1977-10-26 PT PT67194A patent/PT67194B/pt unknown
- 1977-10-27 GB GB44729/77A patent/GB1590155A/en not_active Expired
- 1977-10-27 CA CA289,687A patent/CA1100136A/en not_active Expired
- 1977-10-27 IL IL53236A patent/IL53236A0/xx unknown
- 1977-10-27 NZ NZ185539A patent/NZ185539A/xx unknown
- 1977-10-28 SE SE7712218A patent/SE7712218L/xx unknown
- 1977-10-28 IE IE2206/77A patent/IE45901B1/en unknown
- 1977-10-28 BE BE1008483A patent/BE860314A/xx unknown
- 1977-10-28 DE DE19772748466 patent/DE2748466A1/de not_active Withdrawn
- 1977-10-28 PH PH20380A patent/PH12590A/en unknown
- 1977-10-28 FR FR7732776A patent/FR2369267A1/fr active Granted
- 1977-10-29 GR GR54664A patent/GR70053B/el unknown
- 1977-10-31 AR AR269797A patent/AR223454A1/es active
- 1977-11-01 ZA ZA00776497A patent/ZA776497B/xx unknown
- 1977-11-01 DK DK485277A patent/DK485277A/da unknown
- 1977-11-01 NL NL7712053A patent/NL7712053A/xx not_active Application Discontinuation
- 1977-11-01 AU AU30235/77A patent/AU513679B2/en not_active Expired
- 1977-11-01 HU HU77EI768A patent/HU176231B/hu unknown
- 1977-11-02 PL PL1977212225A patent/PL108610B1/pl unknown
- 1977-11-02 RO RO7792007A patent/RO72900A/ro unknown
- 1977-11-02 RO RO7799435A patent/RO77935A/ro unknown
- 1977-11-02 ES ES463783A patent/ES463783A1/es not_active Expired
- 1977-11-02 JP JP13211177A patent/JPS5356669A/ja active Pending
- 1977-11-02 SU SU772539649A patent/SU812174A3/ru active
- 1977-11-02 ES ES463784A patent/ES463784A1/es not_active Expired
- 1977-11-02 PL PL1977201885A patent/PL109690B1/pl unknown
- 1977-11-02 AT AT0782177A patent/ATA782177A/de not_active Application Discontinuation
- 1977-11-02 CS CS777150A patent/CS211380B2/cs unknown
- 1977-11-02 PL PL1977212226A patent/PL108466B1/pl unknown
- 1977-11-02 DD DD7700201831A patent/DD133795A5/xx unknown
- 1977-11-02 RO RO7799434A patent/RO78300A/ro unknown
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1978
- 1978-08-01 ES ES472276A patent/ES472276A1/es not_active Expired
- 1978-10-03 SU SU782669395A patent/SU845777A3/ru active
- 1978-10-03 SU SU782669355A patent/SU913941A3/ru active
-
1981
- 1981-05-18 SE SE8103107A patent/SE8103107L/sv unknown
- 1981-05-18 SE SE8103106A patent/SE8103106L/sv unknown
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