CS219944B2 - Method of making the racemic and optically unite derivatives of the 1-phenyl-2-cyclohexen-1-alkylamine - Google Patents
Method of making the racemic and optically unite derivatives of the 1-phenyl-2-cyclohexen-1-alkylamine Download PDFInfo
- Publication number
- CS219944B2 CS219944B2 CS817019A CS701981A CS219944B2 CS 219944 B2 CS219944 B2 CS 219944B2 CS 817019 A CS817019 A CS 817019A CS 701981 A CS701981 A CS 701981A CS 219944 B2 CS219944 B2 CS 219944B2
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- CS
- Czechoslovakia
- Prior art keywords
- formula
- compounds
- niederes
- carbon atoms
- racemic
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 3
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 53
- 150000003839 salts Chemical class 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims 2
- 239000007858 starting material Substances 0.000 claims 2
- GAAODRILOUDQTB-UHFFFAOYSA-N 2-methoxy-1,1-dioxo-1,2-benzothiazol-3-one Chemical compound C1=CC=C2S(=O)(=O)N(OC)C(=O)C2=C1 GAAODRILOUDQTB-UHFFFAOYSA-N 0.000 claims 1
- 239000002131 composite material Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 238000005303 weighing Methods 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- -1 hydrocarbon radicals Chemical class 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000001828 Gelatine Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 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 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- MYNLIUPCOLRRLL-UHFFFAOYSA-N 2-[1-(3-methoxyphenyl)cyclohex-2-en-1-yl]-n-methylethanamine Chemical compound C=1C=CC(OC)=CC=1C1(CCNC)CCCC=C1 MYNLIUPCOLRRLL-UHFFFAOYSA-N 0.000 description 2
- KXKUERKNPOCGCT-UHFFFAOYSA-N 2-[1-(3-methoxyphenyl)cyclohex-2-en-1-yl]acetic acid Chemical compound COC1=CC=CC(C2(CC(O)=O)C=CCCC2)=C1 KXKUERKNPOCGCT-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 229960004126 codeine Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
- 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 2
- 229960004193 dextropropoxyphene Drugs 0.000 description 2
- ZBDAMDWKXGTKBT-UHFFFAOYSA-N ethyl 2-cyclohexylacetate Chemical compound CCOC(=O)CC1CCCCC1 ZBDAMDWKXGTKBT-UHFFFAOYSA-N 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- LLCOIQRNSJBFSN-UHFFFAOYSA-N methane;sulfurochloridic acid Chemical compound C.OS(Cl)(=O)=O LLCOIQRNSJBFSN-UHFFFAOYSA-N 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- MRWJNRNJZDUKPX-IUCAKERBSA-N (2s,3s)-2,3-dihydroxy-4-(4-methylphenoxy)-4-oxobutanoic acid Chemical compound CC1=CC=C(OC(=O)[C@@H](O)[C@H](O)C(O)=O)C=C1 MRWJNRNJZDUKPX-IUCAKERBSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- KACQSVYTBQDRGP-UHFFFAOYSA-N 2-(3-methoxyphenyl)cyclohexan-1-one Chemical compound COC1=CC=CC(C2C(CCCC2)=O)=C1 KACQSVYTBQDRGP-UHFFFAOYSA-N 0.000 description 1
- RCIZXFHVCDJFLM-UHFFFAOYSA-N 2-[1-(3-methoxyphenyl)cyclohex-2-en-1-yl]-n,n-dimethylethanamine Chemical compound COC1=CC=CC(C2(CCN(C)C)C=CCCC2)=C1 RCIZXFHVCDJFLM-UHFFFAOYSA-N 0.000 description 1
- JXGPWHGFWOETBV-UHFFFAOYSA-N 2-[1-(3-methoxyphenyl)cyclohex-2-en-1-yl]-n,n-dimethylethanamine;hydrochloride Chemical compound Cl.COC1=CC=CC(C2(CCN(C)C)C=CCCC2)=C1 JXGPWHGFWOETBV-UHFFFAOYSA-N 0.000 description 1
- KWTQWMCFELSGCO-UHFFFAOYSA-N 2-[1-(3-methoxyphenyl)cyclohex-2-en-1-yl]acetaldehyde Chemical compound COC1=CC=CC(C2(CC=O)C=CCCC2)=C1 KWTQWMCFELSGCO-UHFFFAOYSA-N 0.000 description 1
- NHIXWDCCYHGFMD-UHFFFAOYSA-N 2-cyclohex-2-en-1-ylacetaldehyde Chemical compound O=CCC1CCCC=C1 NHIXWDCCYHGFMD-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- CZWMZFMTHRFIPC-UHFFFAOYSA-N 3-[1-(3-methoxyphenyl)cyclohex-2-en-1-yl]-n,n-dimethylpropan-1-amine Chemical compound COC1=CC=CC(C2(CCCN(C)C)C=CCCC2)=C1 CZWMZFMTHRFIPC-UHFFFAOYSA-N 0.000 description 1
- XFHJIZRANHIPTJ-UHFFFAOYSA-N 3-[1-[2-(dimethylamino)ethyl]cyclohex-2-en-1-yl]phenol Chemical compound C=1C=CC(O)=CC=1C1(CCN(C)C)CCCC=C1 XFHJIZRANHIPTJ-UHFFFAOYSA-N 0.000 description 1
- ACZGCWSMSTYWDQ-UHFFFAOYSA-N 3h-1-benzofuran-2-one Chemical compound C1=CC=C2OC(=O)CC2=C1 ACZGCWSMSTYWDQ-UHFFFAOYSA-N 0.000 description 1
- NGUZIGKPTFQHQW-UHFFFAOYSA-N C(C)OC(CC1(C(=CCCC1)CC)C1=CC(=CC=C1)OC)=O Chemical compound C(C)OC(CC1(C(=CCCC1)CC)C1=CC(=CC=C1)OC)=O NGUZIGKPTFQHQW-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 150000000994 L-ascorbates Chemical class 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 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
- 229930006000 Sucrose Natural products 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical class B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 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
- RTKOOMJAGQIBEQ-UHFFFAOYSA-N ethyl 2-[2-hydroxy-1-(3-methoxyphenyl)cyclohexyl]acetate Chemical compound C=1C=CC(OC)=CC=1C1(CC(=O)OCC)CCCCC1O RTKOOMJAGQIBEQ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000008011 inorganic excipient Substances 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- UIEVGJZRKNKEKS-UHFFFAOYSA-N n-(cyclopropylmethyl)-2-[1-(3-methoxyphenyl)cyclohex-2-en-1-yl]-n-methylethanamine Chemical compound COC1=CC=CC(C2(CCN(C)CC3CC3)C=CCCC2)=C1 UIEVGJZRKNKEKS-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000008012 organic excipient Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000007017 scission Effects 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
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical group CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH72480A CH644580A5 (de) | 1980-01-29 | 1980-01-29 | Cyclohexen-derivate. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS219944B2 true CS219944B2 (en) | 1983-03-25 |
Family
ID=4193699
Family Applications (6)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS817019A CS219944B2 (en) | 1980-01-29 | 1981-01-19 | Method of making the racemic and optically unite derivatives of the 1-phenyl-2-cyclohexen-1-alkylamine |
| CS817015A CS219941B2 (en) | 1980-01-29 | 1981-01-19 | Method of making the racemic and optically unite derivatives of the 1-phenyl-2-cyclohexene-1-alcylamine |
| CS81362A CS219940B2 (en) | 1980-01-29 | 1981-01-19 | Method of making the racemic and optically unite derivatives 1-phenyl-2-cyclohexen-1-alcylamide |
| CS817016A CS219942B2 (en) | 1980-01-29 | 1981-01-19 | Method of making the racemic and optically unite derivatives of the 1-phenyl-2-cyclohexene-1-alcylamine |
| CS817017A CS220347B2 (en) | 1980-01-29 | 1981-01-19 | Method of producing racemic and optically uniform 1-phenyl-2-cyclohexene-1-ethylamine derivatives |
| CS817018A CS219943B2 (en) | 1980-01-29 | 1981-01-19 | Method of making the racemic and optically unite derivatives of the 1-phenyl-2-cyclohexene-1-alcylamine |
Family Applications After (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS817015A CS219941B2 (en) | 1980-01-29 | 1981-01-19 | Method of making the racemic and optically unite derivatives of the 1-phenyl-2-cyclohexene-1-alcylamine |
| CS81362A CS219940B2 (en) | 1980-01-29 | 1981-01-19 | Method of making the racemic and optically unite derivatives 1-phenyl-2-cyclohexen-1-alcylamide |
| CS817016A CS219942B2 (en) | 1980-01-29 | 1981-01-19 | Method of making the racemic and optically unite derivatives of the 1-phenyl-2-cyclohexene-1-alcylamine |
| CS817017A CS220347B2 (en) | 1980-01-29 | 1981-01-19 | Method of producing racemic and optically uniform 1-phenyl-2-cyclohexene-1-ethylamine derivatives |
| CS817018A CS219943B2 (en) | 1980-01-29 | 1981-01-19 | Method of making the racemic and optically unite derivatives of the 1-phenyl-2-cyclohexene-1-alcylamine |
Country Status (32)
| Country | Link |
|---|---|
| US (2) | US4336268A (ko) |
| EP (1) | EP0033156B1 (ko) |
| JP (1) | JPS56120650A (ko) |
| KR (6) | KR850000626B1 (ko) |
| AR (1) | AR227906A1 (ko) |
| AT (2) | ATE9895T1 (ko) |
| AU (1) | AU540697B2 (ko) |
| BR (1) | BR8100484A (ko) |
| CA (1) | CA1161064A (ko) |
| CH (1) | CH644580A5 (ko) |
| CS (6) | CS219944B2 (ko) |
| DE (2) | DE3166656D1 (ko) |
| DK (1) | DK15681A (ko) |
| ES (6) | ES8301200A1 (ko) |
| FI (1) | FI801147A7 (ko) |
| FR (1) | FR2479815A1 (ko) |
| GB (1) | GB2068373B (ko) |
| HU (1) | HU182280B (ko) |
| IE (1) | IE50885B1 (ko) |
| IL (1) | IL61961A (ko) |
| IT (1) | IT1135001B (ko) |
| LU (1) | LU83096A1 (ko) |
| MC (1) | MC1365A1 (ko) |
| NL (1) | NL8100403A (ko) |
| NO (1) | NO149958C (ko) |
| NZ (1) | NZ196086A (ko) |
| PH (1) | PH16098A (ko) |
| PT (1) | PT72415B (ko) |
| SE (1) | SE8100403L (ko) |
| YU (1) | YU332180A (ko) |
| ZA (1) | ZA81459B (ko) |
| ZW (1) | ZW31480A1 (ko) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6372919B1 (en) * | 2001-01-11 | 2002-04-16 | Dov Pharmaceutical, Inc. | (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, compositions thereof, and uses as an anti-depressant agent |
| US20060173064A1 (en) * | 2001-08-24 | 2006-08-03 | Lippa Arnold S | (-)-1-(3,4-Dichlorophenyl)-3-azabi cyclo[3.1.0]hexane, compositions thereof, and uses for treating alcohol-related disorders |
| US6569887B2 (en) * | 2001-08-24 | 2003-05-27 | Dov Pharmaceuticals Inc. | (−)-1-(3,4-Dichlorophenyl)-3-azabicyclo[3.1.0]hexane, compositions thereof, and uses as a dopamine-reuptake |
| US20080081834A1 (en) | 2002-07-31 | 2008-04-03 | Lippa Arnold S | Methods and compositions employing bicifadine for treating disability or functional impairment associated with acute pain, chronic pain, or neuropathic disorders |
| US20070043100A1 (en) * | 2005-08-16 | 2007-02-22 | Hagen Eric J | Novel polymorphs of azabicyclohexane |
| US20060100263A1 (en) * | 2004-11-05 | 2006-05-11 | Anthony Basile | Antipyretic compositions and methods |
| RU2008107336A (ru) | 2005-07-27 | 2009-09-10 | Дов Фармасьютикал, Инк. (Us) | Новые 1-арил-з-азабицикло{3.1.0.} гексаны: получение и применение для лечения психоневрологических расстройств |
| US20080045725A1 (en) | 2006-04-28 | 2008-02-21 | Murry Jerry A | Process For The Synthesis of (+) And (-)-1-(3,4-Dichlorophenyl)-3-Azabicyclo[3.1.0]Hexane |
| US8138377B2 (en) * | 2006-11-07 | 2012-03-20 | Dov Pharmaceutical, Inc. | Arylbicyclo[3.1.0]hexylamines and methods and compositions for their preparation and use |
| US20080269348A1 (en) * | 2006-11-07 | 2008-10-30 | Phil Skolnick | Novel Arylbicyclo[3.1.0]Hexylamines And Methods And Compositions For Their Preparation And Use |
| WO2008153937A2 (en) * | 2007-06-06 | 2008-12-18 | Dov Pharmaceutical, Inc. | Novel 1- heteroaryl-3-azabicyclo[3.1.0]hexanes, methods for their preparation and their use as medicaments |
| US9133159B2 (en) | 2007-06-06 | 2015-09-15 | Neurovance, Inc. | 1-heteroaryl-3-azabicyclo[3.1.0]hexanes, methods for their preparation and their use as medicaments |
| US20140206740A1 (en) | 2011-07-30 | 2014-07-24 | Neurovance, Inc. | Use Of (1R,5S)-(+)-(Napthalen-2-yl)-3-Azabicyclo[3.1.0]Hexane In The Treatment Of Conditions Affected By Monoamine Neurotransmitters |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH249052A (de) * | 1944-03-20 | 1947-05-31 | Ag J R Geigy | Verfahren zur Darstellung eines basischen Amids einer 1-Aryl-cycloalkyl-1-carbonsäure. |
| CH249047A (de) * | 1944-03-20 | 1947-05-31 | Ag J R Geigy | Verfahren zur Darstellung eines basischen Esters einer 1-Aryl-cycloalkyl-1-carbonsäure. |
| US2647122A (en) * | 1948-10-01 | 1953-07-28 | Sterling Drug Inc | Tertiary amines and process of preparing them |
| US3109845A (en) * | 1960-02-04 | 1963-11-05 | Thomae Gmbh Dr K | 1-cyclohexyl, 1-cyclohexenyl, 1-furyl, and 1-thienyl, tertiary amino substituted methanes |
| DE1518545A1 (de) * | 1965-04-01 | 1970-01-15 | Boehringer Mannheim Gmbh | Verfahren zur Herstellung neuer Phenylcyclohexylalkylamine und ihrer Salze |
| DE1518663A1 (de) * | 1965-08-02 | 1969-12-18 | Gruenenthal Chemie | Basisch substituierte Cycloalken-derivate und Verfahren zu ihrer Herstellung |
| US3408396A (en) * | 1965-10-22 | 1968-10-29 | Colgate Palmolive Co | alpha-cyclohexyl-3, 4-disubstituted-phenyl acetamides |
| US3485873A (en) * | 1966-12-21 | 1969-12-23 | Sterling Drug Inc | N-benzyl-n-methyl-omega-phenyl-omega-cycloalkyl-lower-alkylamines |
| US3737451A (en) * | 1970-09-23 | 1973-06-05 | Sandoz Ag | Cis-3,4-diaryl-cyclopentylidene-and 1-cyclopentene-1-acetic acids and derivatives |
| US4053637A (en) * | 1971-06-11 | 1977-10-11 | Astra Lakemedal Aktiebolag | Compounds of diphenylcyclopentylamine type and methods for their uses |
| CA1130318A (en) * | 1978-10-11 | 1982-08-24 | Peter M. Muller | Cyclohexadiene derivatives |
-
1980
- 1980-01-29 CH CH72480A patent/CH644580A5/de not_active IP Right Cessation
- 1980-04-10 FI FI801147A patent/FI801147A7/fi not_active Application Discontinuation
- 1980-12-11 CA CA000366550A patent/CA1161064A/en not_active Expired
- 1980-12-19 ZW ZW314/80A patent/ZW31480A1/xx unknown
- 1980-12-30 YU YU03321/80A patent/YU332180A/xx unknown
-
1981
- 1981-01-08 IT IT19047/81A patent/IT1135001B/it active
- 1981-01-14 DK DK15681A patent/DK15681A/da not_active Application Discontinuation
- 1981-01-19 CS CS817019A patent/CS219944B2/cs unknown
- 1981-01-19 CS CS817015A patent/CS219941B2/cs unknown
- 1981-01-19 CS CS81362A patent/CS219940B2/cs unknown
- 1981-01-19 CS CS817016A patent/CS219942B2/cs unknown
- 1981-01-19 CS CS817017A patent/CS220347B2/cs unknown
- 1981-01-19 CS CS817018A patent/CS219943B2/cs unknown
- 1981-01-20 PH PH25103A patent/PH16098A/en unknown
- 1981-01-22 ZA ZA00810459A patent/ZA81459B/xx unknown
- 1981-01-22 NZ NZ196086A patent/NZ196086A/en unknown
- 1981-01-22 IL IL61961A patent/IL61961A/xx unknown
- 1981-01-23 AR AR284052A patent/AR227906A1/es active
- 1981-01-23 SE SE8100403A patent/SE8100403L/xx not_active Application Discontinuation
- 1981-01-26 MC MC811495A patent/MC1365A1/fr unknown
- 1981-01-27 AT AT81100576T patent/ATE9895T1/de active
- 1981-01-27 FR FR8101480A patent/FR2479815A1/fr active Granted
- 1981-01-27 EP EP81100576A patent/EP0033156B1/de not_active Expired
- 1981-01-27 JP JP975781A patent/JPS56120650A/ja active Pending
- 1981-01-27 LU LU83096A patent/LU83096A1/de unknown
- 1981-01-27 DE DE8181100576T patent/DE3166656D1/de not_active Expired
- 1981-01-27 DE DE19813102603 patent/DE3102603A1/de not_active Withdrawn
- 1981-01-27 US US06/228,793 patent/US4336268A/en not_active Expired - Fee Related
- 1981-01-28 GB GB8102555A patent/GB2068373B/en not_active Expired
- 1981-01-28 PT PT72415A patent/PT72415B/pt unknown
- 1981-01-28 AT AT0035581A patent/AT376654B/de not_active IP Right Cessation
- 1981-01-28 IE IE153/81A patent/IE50885B1/en unknown
- 1981-01-28 NO NO810297A patent/NO149958C/no unknown
- 1981-01-28 NL NL8100403A patent/NL8100403A/nl not_active Application Discontinuation
- 1981-01-28 KR KR1019810000259A patent/KR850000626B1/ko not_active Expired
- 1981-01-28 ES ES498866A patent/ES8301200A1/es not_active Expired
- 1981-01-28 BR BR8100484A patent/BR8100484A/pt unknown
- 1981-01-28 HU HU81178A patent/HU182280B/hu unknown
- 1981-01-29 AU AU66719/81A patent/AU540697B2/en not_active Ceased
- 1981-10-29 ES ES506686A patent/ES506686A0/es active Granted
- 1981-10-29 ES ES506685A patent/ES506685A0/es active Granted
- 1981-10-29 ES ES506684A patent/ES506684A0/es active Granted
- 1981-10-29 ES ES506687A patent/ES8301885A1/es not_active Expired
- 1981-10-29 ES ES506688A patent/ES506688A0/es active Granted
-
1982
- 1982-03-24 US US06/361,290 patent/US4448991A/en not_active Expired - Fee Related
-
1984
- 1984-08-01 KR KR1019840004584A patent/KR850000627B1/ko not_active Expired
- 1984-08-01 KR KR1019840004585A patent/KR840001554B1/ko not_active Expired
- 1984-08-01 KR KR1019840004583A patent/KR840001553B1/ko not_active Expired
- 1984-08-01 KR KR1019840004581A patent/KR840001551B1/ko not_active Expired
- 1984-08-01 KR KR1019840004582A patent/KR840001552B1/ko not_active Expired
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