JPS6134426B2 - - Google Patents
Info
- Publication number
- JPS6134426B2 JPS6134426B2 JP52059295A JP5929577A JPS6134426B2 JP S6134426 B2 JPS6134426 B2 JP S6134426B2 JP 52059295 A JP52059295 A JP 52059295A JP 5929577 A JP5929577 A JP 5929577A JP S6134426 B2 JPS6134426 B2 JP S6134426B2
- Authority
- JP
- Japan
- Prior art keywords
- cis
- trans
- methyl
- compounds
- hexahydro
- 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 description 84
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 238000002844 melting Methods 0.000 description 45
- 230000008018 melting Effects 0.000 description 45
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 30
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 30
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 29
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- -1 sodium trimethoxyborohydride Chemical compound 0.000 description 11
- BFJMHTOBRRZELQ-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C(I)=NNC2=C1 BFJMHTOBRRZELQ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 229910052681 coesite Inorganic materials 0.000 description 7
- 229910052906 cristobalite Inorganic materials 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 235000012239 silicon dioxide Nutrition 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 229910052682 stishovite Inorganic materials 0.000 description 7
- 229910052905 tridymite Inorganic materials 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 6
- 229910010082 LiAlH Inorganic materials 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 150000002081 enamines Chemical class 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 4
- QLSJOGIENLKPTF-BTJKTKAUSA-N (z)-but-2-enedioic acid;pyridine Chemical compound C1=CC=NC=C1.OC(=O)\C=C/C(O)=O QLSJOGIENLKPTF-BTJKTKAUSA-N 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- LNFLVFXWOCZBMF-UHFFFAOYSA-N cyclohepta[c]pyrrole Chemical compound C1=CC=CC=C2C=NC=C21 LNFLVFXWOCZBMF-UHFFFAOYSA-N 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000011976 maleic acid Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 3
- 230000001387 anti-histamine Effects 0.000 description 3
- 230000000794 anti-serotonin Effects 0.000 description 3
- 239000000739 antihistaminic agent Substances 0.000 description 3
- 239000003420 antiserotonin agent Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 125000000468 ketone group Chemical group 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- SXLUCYUNXMFXTK-UHFFFAOYSA-N oxepino[4,5-c]pyridine Chemical compound C1=COC=CC2=CC=NC=C21 SXLUCYUNXMFXTK-UHFFFAOYSA-N 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000001624 sedative effect Effects 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 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 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000006027 Birch reduction reaction Methods 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- SLENXKMKHOABFS-BTJKTKAUSA-N OC(=O)\C=C/C(O)=O.C1=CSC=CC2=CC=NC=C21 Chemical compound OC(=O)\C=C/C(O)=O.C1=CSC=CC2=CC=NC=C21 SLENXKMKHOABFS-BTJKTKAUSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000003874 central nervous system depressant Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000002631 hypothermal effect Effects 0.000 description 2
- KPJPHPFMCOKUMW-UHFFFAOYSA-N iodomethane Chemical compound I[CH2] KPJPHPFMCOKUMW-UHFFFAOYSA-N 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 230000000701 neuroleptic effect Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- 150000003233 pyrroles Chemical class 0.000 description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 2
- 229960003147 reserpine Drugs 0.000 description 2
- 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 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000000932 sedative agent Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- OPXSBNSQDBIFMK-BTJKTKAUSA-N (Z)-but-2-enedioic acid 2H-cyclohepta[c]pyridine Chemical compound OC(=O)\C=C/C(O)=O.C1=CC=CC2=CNC=CC2=C1 OPXSBNSQDBIFMK-BTJKTKAUSA-N 0.000 description 1
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
- HCLXLZGAYCTHQJ-UHFFFAOYSA-N 1h-cyclohepta[b]pyridine Chemical compound C1=CC=CC=C2NC=CC=C21 HCLXLZGAYCTHQJ-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- CDZCREIHDRCTHZ-UHFFFAOYSA-N 2h-cyclohepta[c]pyridine Chemical compound C1=CC=CC2=CNC=CC2=C1 CDZCREIHDRCTHZ-UHFFFAOYSA-N 0.000 description 1
- KYXLYJWGRDSBIK-UHFFFAOYSA-N 5h-pyrido[3,2-b]azepine Chemical group N1C=CC=CC2=NC=CC=C12 KYXLYJWGRDSBIK-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- WUEBKKCYOAZLJV-UHFFFAOYSA-N C=1NC=CC=2C1C=CN=CC2 Chemical compound C=1NC=CC=2C1C=CN=CC2 WUEBKKCYOAZLJV-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 238000006824 Eschweiler-Clarke methylation reaction Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- HZDATNPNIJGYLC-UHFFFAOYSA-N [I-].C=1[NH2+]C=CC=2C1C=CC=CC2 Chemical compound [I-].C=1[NH2+]C=CC=2C1C=CC=CC2 HZDATNPNIJGYLC-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
- 229960004046 apomorphine Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- PCKRALVYSUGNGV-UHFFFAOYSA-N cs-m2771 Chemical compound C1C2=CC=CC=C2C2CCN(C)CC2C2=CC=CC=C21 PCKRALVYSUGNGV-UHFFFAOYSA-N 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 239000012259 ether extract Substances 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
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- CTVOZUFKICZROL-UHFFFAOYSA-N pyrrolo[3,2-b]azepine Chemical class C1=CC=CC2=NC=CC2=N1 CTVOZUFKICZROL-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000000698 schizophrenic effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/70—[b]- or [c]-condensed containing carbocyclic rings other than six-membered
-
- 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
- C07D221/18—Ring systems of four or more rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Anesthesiology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL7605526A NL7605526A (nl) | 1976-05-24 | 1976-05-24 | Nieuwe tetracyclische derivaten. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS532465A JPS532465A (en) | 1978-01-11 |
| JPS6134426B2 true JPS6134426B2 (US07534539-20090519-C00280.png) | 1986-08-07 |
Family
ID=19826245
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5929577A Granted JPS532465A (en) | 1976-05-24 | 1977-05-20 | Novel tetracyclic derivative* its preparation and formulations containing same |
| JP61007790A Granted JPS61178965A (ja) | 1976-05-24 | 1986-01-17 | 新規な四環式誘導体 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61007790A Granted JPS61178965A (ja) | 1976-05-24 | 1986-01-17 | 新規な四環式誘導体 |
Country Status (18)
Families Citing this family (86)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0007450A1 (de) * | 1978-07-07 | 1980-02-06 | Ciba-Geigy Ag | Azatetracyclische Carbonitrile, ihre Herstellung, pharmazeutische Präparate, die diese enthalten und deren Verwendung |
| ATE9159T1 (de) * | 1979-12-10 | 1984-09-15 | Ciba-Geigy Ag | Azatetracyclische carbonitrile. |
| FR2504140A1 (fr) * | 1981-04-16 | 1982-10-22 | Centre Nat Rech Scient | Nouveaux derives tetracycliques de la dibenzazepine, leur procede de preparation et les compositions pharmaceutiques en renfermant |
| DE3372369D1 (de) * | 1982-05-18 | 1987-08-13 | Hoffmann La Roche | Pyrrole (3,4-d)(2)benzazepine derivatives |
| JPS62101941U (US07534539-20090519-C00280.png) * | 1985-12-16 | 1987-06-29 | ||
| IE62754B1 (en) * | 1988-08-26 | 1995-02-22 | Akzo Nv | Tetracyclic antidepressants |
| EP0569096A1 (en) * | 1992-05-08 | 1993-11-10 | Akzo Nobel N.V. | Depot preparation |
| WO1994022858A1 (en) * | 1993-04-06 | 1994-10-13 | Abbott Laboratories | Tetracyclic compounds as dopamine agonists |
| CA2182981C (en) * | 1994-03-02 | 2006-10-17 | Leonardus Petrus Carla Delbressine | Sublingual or buccal pharmaceutical composition |
| JP3274579B2 (ja) * | 1995-01-12 | 2002-04-15 | 住友製薬株式会社 | 脳血管障害に伴う精神症候治療剤 |
| DK0892793T3 (da) * | 1996-04-12 | 2003-07-21 | Janssen Pharmaceutica Nv | Substituerede tetracykliske tetrahydrofuranderivater |
| PL337027A1 (en) * | 1997-05-26 | 2000-07-31 | Akzo Nobel Nv | Salts of aromatic sulphonic acids |
| HRP20020305A8 (en) * | 2002-04-10 | 2009-03-31 | GlaxoSmithKline istra�iva�ki centar Zagreb d.o.o. | 2-thia-dibenzoazulenes as inhibitors of tumour necrosis factor production and intermediates for the preparation thereof |
| HRP20020441A2 (en) * | 2002-05-21 | 2003-12-31 | Pliva D D | 1-oxa-dibenzoazulen as inhibitor of production of tumor necrosis factors and intermediate for preparation thereof |
| HRP20030160A2 (en) * | 2003-03-06 | 2005-04-30 | Pliva-Istra�iva�ki institut d.o.o. | 1-thiadibenzoazulene derivatives and biological action thereof |
| WO2004100992A2 (en) * | 2003-05-16 | 2004-11-25 | Pfizer Products Inc. | Therapeutic combinations of atypical antipsychotics with gaba modulators, anticonvulsants or benzodiazapines |
| HRP20030885A2 (en) * | 2003-11-03 | 2005-08-31 | Pliva-Istra�iva�ki institut d.o.o. | USE OF 2-THIA-DIBENZO[e,h]AZULENES FOR THE MANUFACTURE OF PHARMACEUTICAL FORMULATIONS FOR THE TREATMENT AND PREVENTION OF CENTRAL NERVOUS SYYTEM DISEASES AND DISORDERS |
| HRP20030953A2 (en) * | 2003-11-21 | 2005-10-31 | Pliva-Istra�iva�ki institut d.o.o. | PREPARATION OF 1-AZA-2-OXA-DIBENZO[e,h]AZULENES AND THEIR USE FOR THE MANUFACTURE OF PHARMACEUTICAL FORMULATIONS FOR THE TREATMENT AND PREVENTION OF CENTRAL NERVOUS SYSTEM DISEASES AND DISORDERS |
| HRP20030955A2 (en) * | 2003-11-21 | 2005-08-31 | Pliva-Istra�iva�ki institut d.o.o. | USE OF 1-OXADIBENZO[e,h]AZULENES FOR THE MANUFACTURE OF PHARMACEUTICAL FORMULATIONS FOR THE TREATMENT AND PREVENTION OF CENTRAL NERVOUS SYSTEM DISEASES AND DISORDERS |
| HRP20030958A2 (en) * | 2003-11-21 | 2005-08-31 | Pliva-Istra�iva�ki institut d.o.o. | USE OF 1,3-DIAZA-DIBENZO[e,h]AZULENES FOR THE MANUFACTURE OF THE TREATMENT AND PREVENTION OF CENTRAL NERVOUS SYSTEM DISEASES AND DISORDERS |
| HRP20030956A2 (en) * | 2003-11-21 | 2005-08-31 | Pliva-Istra�iva�ki institut d.o.o. | USE OF 1,2-DIAZA-DIBENZO[e,h]AZULENES FOR THE MANU |
| HRP20030959A2 (US07534539-20090519-C00280.png) * | 2003-11-21 | 2005-10-31 | Pliva-Istra�iva�ki institut d.o.o. | |
| HRP20030957A2 (en) * | 2003-11-21 | 2005-08-31 | Pliva-Istra�iva�ki institut d.o.o. | USE OF 1-THIA-3-AZA-DIBENZO[e,h]AZULENES FOR THE MANUFACTURE OF PHARMACEUTICAL FORMULATIONS FOR THE TREATMENT AND PREVENTION OF CENTRAL NERVOUS SYSTEM DISEASES AND DISORDERS |
| HRP20030954A2 (en) * | 2003-11-21 | 2005-08-31 | Pliva D.D. | USE OF 1-AZA-DIBENZO[e,h]AZULENES FOR THE MANUFACTURENT AND PREVENTION OF CENTRAL NERVOUS SYSTEM DISEASES AND DISORDERS |
| HRP20040104A2 (en) * | 2004-01-30 | 2005-10-31 | Pliva-Istra�iva�ki institut d.o.o. | Use of benzonaphthoazulenes for the manufacture of pharmaceutical formulations for the treatment and prevention of central nervous system diseases and disorders |
| CN1917882A (zh) * | 2004-02-13 | 2007-02-21 | 辉瑞产品公司 | 非典型抗精神病药物与促肾上腺皮质激素释放因子拮抗剂的治疗剂组合 |
| EP1753460A2 (en) * | 2004-05-11 | 2007-02-21 | Pfizer Products Inc. | Combination of atypical antipsychotics and 5-ht1b receptor antagonists |
| US20060084692A1 (en) * | 2004-10-15 | 2006-04-20 | Pfizer Inc. | Treatment of bipolar disorders and associated symptoms |
| PT1710241E (pt) * | 2005-04-07 | 2009-12-10 | Organon Nv | Compostos intermediários para preparação de trans-5-cloro-2- metil-2,3,3a,12b-tetra-hidro-1h-dibenz[2,3:6,7]oxepino- [4,5-c]pirrol |
| US7872147B2 (en) * | 2005-04-07 | 2011-01-18 | N. V. Organon | Intermediate compounds for the preparation of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole |
| RU2405786C2 (ru) * | 2005-04-07 | 2010-12-10 | Н.В. Органон | Кристаллическая форма малеата азенапина |
| US7741358B2 (en) * | 2005-04-14 | 2010-06-22 | N.V. Organon | Crystal form of asenapine maleate |
| WO2007046554A1 (ja) * | 2005-10-21 | 2007-04-26 | Sumitomo Chemical Company, Limited | ジベンゾオキセピノピロール化合物の製造方法、その中間体及び該中間体の製造方法 |
| TW200817414A (en) * | 2006-07-05 | 2008-04-16 | Organon Nv | Process for the preparation of asenapine and intermediate products used in said process |
| US7750167B2 (en) * | 2006-07-05 | 2010-07-06 | N.V. Organon | Process for the preparation of asenapine and intermediate products used in said process |
| WO2008040816A1 (en) * | 2006-10-06 | 2008-04-10 | N.V. Organon | Amorphous asenapine and processes for preparing same |
| US7875729B2 (en) * | 2007-01-05 | 2011-01-25 | Synthon Bv | Process for making asenapine |
| WO2008148515A1 (en) * | 2007-06-05 | 2008-12-11 | Synthon B.V. | Intranasal administration of asenapine and pharmaceutical compositions therefor |
| JP5245428B2 (ja) | 2007-07-06 | 2013-07-24 | 住友化学株式会社 | トランス−ジベンゾオキセノピロール化合物の製造方法およびその中間体 |
| CA2710800A1 (en) * | 2008-01-04 | 2009-07-16 | N.V. Organon | Process for the preparation of asenapine and intermediate products used in said process |
| WO2009104080A2 (en) | 2008-02-20 | 2009-08-27 | Targia Pharmaceuticals | Cns pharmaceutical compositions and methods of use |
| EP2321011A1 (en) * | 2008-06-25 | 2011-05-18 | Pfizer Inc. | Diaryl compounds and uses thereof |
| RU2012102247A (ru) | 2009-06-24 | 2013-07-27 | Мсд Осс Б.В. | Инъекционные композиции, содержащие асенапин и способ лечения с их применением |
| TW201118102A (en) | 2009-07-29 | 2011-06-01 | Organon Nv | Hydroxyasenapine compounds, derivatives thereof and pharmaceutical compositions comprising same |
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| ES2466767T3 (es) | 2010-07-29 | 2014-06-11 | Laboratorios Lesvi, S.L. | Nuevo proceso para la preparación de asenapina |
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| WO2012066565A2 (en) | 2010-11-16 | 2012-05-24 | Cadila Healthcare Limited | Asenapine maleate amorphous and crystalline form and process for preparation thereof |
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| EP2468751B1 (en) | 2010-12-24 | 2016-03-16 | Medichem, S.A. | Processes for the preparation of 5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrole |
| WO2012123325A1 (en) | 2011-03-11 | 2012-09-20 | Medichem S.A. | NEW CRYSTAL FORMS OF THE SALT OF TRANS-5-CHLORO-2-METHYL-2,3,3A,12b-TETRAHYDRO-1H-DIBENZO[2,3:6,7]OXEPINO[4,5-c]PYRROLE WITH MALEIC ACID |
| ITMI20110734A1 (it) | 2011-05-02 | 2012-11-03 | Olon Spa | Sali cristallini di asenapina |
| EP2524921A1 (en) * | 2011-05-17 | 2012-11-21 | Sandoz AG | Novel Crystalline Salts of Asenapine |
| EP2524919A1 (en) | 2011-05-17 | 2012-11-21 | Sandoz AG | Novel crystalline salts of Asenapine with organic Di-acids and Tri-acids |
| US9533994B2 (en) | 2011-05-18 | 2017-01-03 | Laboratorios Lesvi S.L. | Monoclinic crystalline form of asenapine maleate with a specific particle size distribution |
| EP2709616B1 (en) | 2011-05-18 | 2018-01-24 | Laboratorios Lesvi, S.L. | Synthesis of a stable micronised monoclinic form of asenapine maleate |
| WO2013024492A2 (en) | 2011-07-01 | 2013-02-21 | Megafine Pharma (P) Ltd. | A process for the preparation of asenapine and novel salts thereof |
| WO2013011461A1 (en) | 2011-07-20 | 2013-01-24 | Ranbaxy Laboratories Limited | Process for the preparation of asenapine maleate |
| WO2013035109A1 (en) | 2011-09-08 | 2013-03-14 | Mylan Laboratories Ltd | Improved process for the preparation of asenapine maleate |
| EP2572703A1 (en) | 2011-09-21 | 2013-03-27 | Hexal AG | Compressed oral dosage form for asenapine maleate |
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Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH501007A (de) * | 1968-11-27 | 1970-12-31 | Ciba Geigy Ag | Verfahren zur Herstellung von neuen Thiepin- und Oxepinderivaten |
| NL178593C (nl) * | 1974-01-31 | 1986-04-16 | Akzo Nv | Werkwijze ter bereiding van een farmaceutisch preparaat op basis van een tetracyclische verbinding en werkwijze voor de bereiding van de daarbij te gebruiken tetracyclische verbindingen. |
| AU469026B2 (en) * | 1974-11-07 | 1976-01-29 | Ciba-Geigy Ag | New azepine derivatives and process forthe production thereof |
-
1976
- 1976-05-24 NL NL7605526A patent/NL7605526A/xx not_active Application Discontinuation
-
1977
- 1977-05-09 ZA ZA00772752A patent/ZA772752B/xx unknown
- 1977-05-13 GB GB20275/77A patent/GB1567862A/en not_active Expired
- 1977-05-17 IE IE1013/77A patent/IE45419B1/en not_active IP Right Cessation
- 1977-05-18 FR FR7715413A patent/FR2352800A1/fr active Granted
- 1977-05-18 US US05/798,222 patent/US4145434A/en not_active Expired - Lifetime
- 1977-05-20 AU AU25331/77A patent/AU509073B2/en not_active Expired
- 1977-05-20 CH CH626477A patent/CH633536A5/de not_active IP Right Cessation
- 1977-05-20 JP JP5929577A patent/JPS532465A/ja active Granted
- 1977-05-20 SE SE7705957A patent/SE436202B/xx not_active IP Right Cessation
- 1977-05-21 ES ES459024A patent/ES459024A1/es not_active Expired
- 1977-05-23 BE BE177807A patent/BE854915A/xx not_active IP Right Cessation
- 1977-05-23 DE DE19772723209 patent/DE2723209A1/de not_active Withdrawn
- 1977-05-23 DE DE2760372A patent/DE2760372C2/de not_active Expired - Lifetime
- 1977-05-23 FI FI771635A patent/FI65238C/fi not_active IP Right Cessation
- 1977-05-23 HU HU77AO447A patent/HU173795B/hu unknown
- 1977-05-23 LU LU77387A patent/LU77387A1/xx unknown
- 1977-05-24 CA CA279,010A patent/CA1122976A/en not_active Expired
- 1977-05-24 DK DK227477A patent/DK157868C/da not_active IP Right Cessation
-
1978
- 1978-06-01 ES ES470407A patent/ES470407A1/es not_active Expired
- 1978-06-01 ES ES470408A patent/ES470408A1/es not_active Expired
-
1982
- 1982-06-07 CH CH351282A patent/CH637382A5/de not_active IP Right Cessation
-
1986
- 1986-01-17 JP JP61007790A patent/JPS61178965A/ja active Granted
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