FI65242C - Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 1,2,3,4,10,10a-hexahydro-bens(g)isokinoliner och deras syra-additionssalter - Google Patents
Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 1,2,3,4,10,10a-hexahydro-bens(g)isokinoliner och deras syra-additionssalter Download PDFInfo
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- FI65242C FI65242C FI771986A FI771986A FI65242C FI 65242 C FI65242 C FI 65242C FI 771986 A FI771986 A FI 771986A FI 771986 A FI771986 A FI 771986A FI 65242 C FI65242 C FI 65242C
- Authority
- FI
- Finland
- Prior art keywords
- formula
- compounds
- alkyl
- carbon atoms
- hydrogen
- Prior art date
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- 230000001225 therapeutic effect Effects 0.000 title description 3
- 238000005057 refrigeration Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 72
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 3
- 230000002152 alkylating effect Effects 0.000 claims description 2
- -1 stem with 9- 35 Chemical group 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims 1
- 235000020357 syrup Nutrition 0.000 claims 1
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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 8
- 230000000202 analgesic effect Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 206010044565 Tremor Diseases 0.000 description 7
- 238000010171 animal model Methods 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000008602 contraction Effects 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 230000003187 abdominal effect Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 4
- 206010001488 Aggression Diseases 0.000 description 4
- 208000009132 Catalepsy Diseases 0.000 description 4
- 206010015995 Eyelid ptosis Diseases 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 206010047853 Waxy flexibility Diseases 0.000 description 4
- 230000001430 anti-depressive effect Effects 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 201000003004 ptosis Diseases 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 229960005333 tetrabenazine Drugs 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- ZDQCLDBVVQUHDH-UHFFFAOYSA-N 6h-isoquinolin-5-one Chemical compound N1=CC=C2C(=O)CC=CC2=C1 ZDQCLDBVVQUHDH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002537 isoquinolines Chemical class 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 2
- 229940000681 5-hydroxytryptophan Drugs 0.000 description 2
- KSDPQKMYYDMWQB-UHFFFAOYSA-N 5-phenyl-2-propan-2-yl-3,4,10,10a-tetrahydro-1h-benzo[g]isoquinoline Chemical compound C12=CC=CC=C2CC2CN(C(C)C)CCC2=C1C1=CC=CC=C1 KSDPQKMYYDMWQB-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 230000016571 aggressive behavior Effects 0.000 description 2
- 208000012761 aggressive behavior Diseases 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000002631 hypothermal effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000011368 organic material Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- LDCYZAJDBXYCGN-UHFFFAOYSA-N oxitriptan Natural products C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MWXCFGOEHFQGIK-UHFFFAOYSA-N 3-benzyl-1-ethoxycarbonylpiperidine-4-carboxylic acid Chemical compound C1N(C(=O)OCC)CCC(C(O)=O)C1CC1=CC=CC=C1 MWXCFGOEHFQGIK-UHFFFAOYSA-N 0.000 description 1
- XCQGHTMUTPODBU-UHFFFAOYSA-N 3-methyl-4-phenyl-1,2,3,4-tetrahydrobenzo[g]isoquinoline Chemical compound CC1NCC2=CC3=CC=CC=C3C=C2C1C1=CC=CC=C1 XCQGHTMUTPODBU-UHFFFAOYSA-N 0.000 description 1
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
- XRRQQHIQGYVQDJ-FBIGCWIYSA-N C(C)(C)N1C[C@@H]2CC3=C(C([C@H]2CC1)(O)C1=CC=CC=C1)C=CC=C3 Chemical compound C(C)(C)N1C[C@@H]2CC3=C(C([C@H]2CC1)(O)C1=CC=CC=C1)C=CC=C3 XRRQQHIQGYVQDJ-FBIGCWIYSA-N 0.000 description 1
- GTDHIJCVZOUVLD-UHFFFAOYSA-N C1C2=C3C=CN=CC3=CC1=CC=C2 Chemical compound C1C2=C3C=CN=CC3=CC1=CC=C2 GTDHIJCVZOUVLD-UHFFFAOYSA-N 0.000 description 1
- CHVQHZYTAPCJRW-UHFFFAOYSA-N CC(C)N1CCC2=C(C3=CC=CC=C3CC2C1)C4=CC=C(C=C4)Cl Chemical compound CC(C)N1CCC2=C(C3=CC=CC=C3CC2C1)C4=CC=C(C=C4)Cl CHVQHZYTAPCJRW-UHFFFAOYSA-N 0.000 description 1
- SAFQVAQCAQXHEC-UHFFFAOYSA-N CC(C)N1CCC2=CC3=CC=CC=C3CC2C1 Chemical compound CC(C)N1CCC2=CC3=CC=CC=C3CC2C1 SAFQVAQCAQXHEC-UHFFFAOYSA-N 0.000 description 1
- OEJPZJNZBZMQLM-UHFFFAOYSA-N CC1C2CCN(CC2=CC3=CC=CCC13)C(C)C Chemical compound CC1C2CCN(CC2=CC3=CC=CCC13)C(C)C OEJPZJNZBZMQLM-UHFFFAOYSA-N 0.000 description 1
- ZNPLRJHYPSOISR-UHFFFAOYSA-N CCOC(=O)N1CC=C(C(C1)CC2=CC=CC=C2)C#N Chemical compound CCOC(=O)N1CC=C(C(C1)CC2=CC=CC=C2)C#N ZNPLRJHYPSOISR-UHFFFAOYSA-N 0.000 description 1
- PHYUUINIALGROP-UHFFFAOYSA-N CN1CCC2C(C3CC=CC=C3C=C2C1)C4=CC=C(C=C4)Cl Chemical compound CN1CCC2C(C3CC=CC=C3C=C2C1)C4=CC=C(C=C4)Cl PHYUUINIALGROP-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 206010037218 Psychopathic personality Diseases 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- 241000555745 Sciuridae Species 0.000 description 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000002539 anti-aggressive effect Effects 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 230000002716 ataractic effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000001604 effect on 5-hydroxytryptophan Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- GZYOMNVTMULSSV-UHFFFAOYSA-N ethyl 1h-isoquinoline-2-carboxylate Chemical compound C1=CC=C2C=CN(C(=O)OCC)CC2=C1 GZYOMNVTMULSSV-UHFFFAOYSA-N 0.000 description 1
- VKZRTEYQYHCQPM-UHFFFAOYSA-N ethyl 3-benzyl-4-cyano-4-hydroxypiperidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CCC(O)(C#N)C1CC1=CC=CC=C1 VKZRTEYQYHCQPM-UHFFFAOYSA-N 0.000 description 1
- SSRXCUGKKUNZJL-UHFFFAOYSA-N ethyl 3-benzyl-4-cyanopiperidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CCC(C#N)C1CC1=CC=CC=C1 SSRXCUGKKUNZJL-UHFFFAOYSA-N 0.000 description 1
- QBWFQPVWLBVNNK-UHFFFAOYSA-N ethyl 3-benzyl-4-oxopiperidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CCC(=O)C1CC1=CC=CC=C1 QBWFQPVWLBVNNK-UHFFFAOYSA-N 0.000 description 1
- WPIYPWPXFHJGOJ-UHFFFAOYSA-N ethyl 5-benzyl-4-cyano-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OCC)CCC(C#N)=C1CC1=CC=CC=C1 WPIYPWPXFHJGOJ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000468 ketone group Chemical group 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
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 238000005406 washing Methods 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
- C07D221/06—Ring systems of three rings
- C07D221/08—Aza-anthracenes
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
- C07D211/66—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having a hetero atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (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)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI832464A FI832464L (fi) | 1976-07-06 | 1977-06-27 | Foerfarande foer framstaellning av nya bens(g)isokinolinderivat |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH863276A CH622783A5 (en) | 1976-07-06 | 1976-07-06 | Process for the preparation of novel hexahydrobenz[g]isoquinoline derivatives |
| CH863176 | 1976-07-06 | ||
| CH863176A CH622782A5 (en) | 1976-07-06 | 1976-07-06 | Process for the preparation of novel hexahydrobenz[g]isoquinoline derivatives |
| CH863276 | 1976-07-06 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI771986A7 FI771986A7 (enExample) | 1978-01-07 |
| FI65242B FI65242B (fi) | 1983-12-30 |
| FI65242C true FI65242C (fi) | 1984-04-10 |
Family
ID=25703556
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI771986A FI65242C (fi) | 1976-07-06 | 1977-06-27 | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 1,2,3,4,10,10a-hexahydro-bens(g)isokinoliner och deras syra-additionssalter |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4150136A (enExample) |
| JP (1) | JPS537681A (enExample) |
| AT (1) | AT366369B (enExample) |
| CA (1) | CA1094561A (enExample) |
| DE (1) | DE2728831A1 (enExample) |
| DK (1) | DK285077A (enExample) |
| ES (2) | ES460371A1 (enExample) |
| FI (1) | FI65242C (enExample) |
| FR (1) | FR2357547A1 (enExample) |
| GB (1) | GB1582783A (enExample) |
| IE (1) | IE45241B1 (enExample) |
| IL (1) | IL52449A (enExample) |
| MY (1) | MY8400058A (enExample) |
| NL (1) | NL7707307A (enExample) |
| NZ (1) | NZ184547A (enExample) |
| PH (1) | PH14074A (enExample) |
| PT (1) | PT66758B (enExample) |
| SE (2) | SE7707445L (enExample) |
| SU (1) | SU692559A3 (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4678791A (en) * | 1985-05-07 | 1987-07-07 | Pennwalt Corporation | 6-phenyl-1,2-3,4,4a,5-6,10b-octahydrobenz(h)isoquinolines useful for treating depression |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3325803A (en) * | 1964-10-01 | 1967-06-13 | Ibm | Deflection control circuit |
-
1977
- 1977-06-27 FI FI771986A patent/FI65242C/fi not_active IP Right Cessation
- 1977-06-27 DE DE19772728831 patent/DE2728831A1/de not_active Withdrawn
- 1977-06-27 DK DK285077A patent/DK285077A/da not_active Application Discontinuation
- 1977-06-28 SE SE7707445A patent/SE7707445L/xx not_active Application Discontinuation
- 1977-06-30 US US05/811,585 patent/US4150136A/en not_active Expired - Lifetime
- 1977-06-30 GB GB27304/77A patent/GB1582783A/en not_active Expired
- 1977-07-01 NL NL7707307A patent/NL7707307A/xx unknown
- 1977-07-04 IL IL52449A patent/IL52449A/xx unknown
- 1977-07-04 NZ NZ184547A patent/NZ184547A/xx unknown
- 1977-07-04 PT PT66758A patent/PT66758B/pt unknown
- 1977-07-04 CA CA281,898A patent/CA1094561A/en not_active Expired
- 1977-07-04 IE IE1382/77A patent/IE45241B1/en unknown
- 1977-07-04 ES ES460371A patent/ES460371A1/es not_active Expired
- 1977-07-05 PH PH19950A patent/PH14074A/en unknown
- 1977-07-05 JP JP7956677A patent/JPS537681A/ja active Pending
- 1977-07-05 AT AT0477577A patent/AT366369B/de not_active IP Right Cessation
- 1977-07-06 SU SU772499556A patent/SU692559A3/ru active
- 1977-07-06 FR FR7720814A patent/FR2357547A1/fr active Granted
-
1979
- 1979-01-16 ES ES476889A patent/ES476889A1/es not_active Expired
-
1982
- 1982-12-23 SE SE8207394A patent/SE8207394D0/xx not_active Application Discontinuation
-
1984
- 1984-12-30 MY MY58/84A patent/MY8400058A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL52449A (en) | 1981-09-13 |
| FI771986A7 (enExample) | 1978-01-07 |
| SU692559A3 (ru) | 1979-10-15 |
| DE2728831A1 (de) | 1978-01-19 |
| PT66758A (fr) | 1977-08-01 |
| AT366369B (de) | 1982-04-13 |
| MY8400058A (en) | 1984-12-31 |
| SE7707445L (sv) | 1978-01-07 |
| NZ184547A (en) | 1980-08-26 |
| GB1582783A (en) | 1981-01-14 |
| NL7707307A (nl) | 1978-01-10 |
| CA1094561A (en) | 1981-01-27 |
| IE45241B1 (en) | 1982-07-14 |
| PH14074A (en) | 1981-01-26 |
| PT66758B (fr) | 1979-03-12 |
| SE8207394L (sv) | 1982-12-23 |
| FI65242B (fi) | 1983-12-30 |
| SE8207394D0 (sv) | 1982-12-23 |
| ATA477577A (de) | 1981-08-15 |
| ES460371A1 (es) | 1979-05-01 |
| IL52449A0 (en) | 1977-10-31 |
| FR2357547A1 (fr) | 1978-02-03 |
| JPS537681A (en) | 1978-01-24 |
| US4150136A (en) | 1979-04-17 |
| IE45241L (en) | 1978-01-06 |
| FR2357547B1 (enExample) | 1980-02-15 |
| ES476889A1 (es) | 1979-07-16 |
| AU2677177A (en) | 1979-01-11 |
| DK285077A (da) | 1978-01-07 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: SANDOZ AG |