FI65238C - Foerfarande foer framstaellning av terapeutiskt anvaendbara teracykliska foereningar - Google Patents
Foerfarande foer framstaellning av terapeutiskt anvaendbara teracykliska foereningar Download PDFInfo
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- FI65238C FI65238C FI771635A FI771635A FI65238C FI 65238 C FI65238 C FI 65238C FI 771635 A FI771635 A FI 771635A FI 771635 A FI771635 A FI 771635A FI 65238 C FI65238 C FI 65238C
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- 230000001225 therapeutic effect Effects 0.000 title 2
- 150000001875 compounds Chemical class 0.000 claims description 61
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 11
- 230000000794 anti-serotonin Effects 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 239000000739 antihistaminic agent Substances 0.000 claims description 9
- 239000003420 antiserotonin agent Substances 0.000 claims description 9
- 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 claims description 8
- 230000001387 anti-histamine Effects 0.000 claims description 8
- 210000003169 central nervous system Anatomy 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 150000002081 enamines Chemical class 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000003874 central nervous system depressant Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- 229940125715 antihistaminic agent Drugs 0.000 claims 1
- 239000003086 colorant Substances 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 239000011800 void material Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 description 23
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 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 10
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 10
- 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 10
- 229960003147 reserpine Drugs 0.000 description 10
- 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 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- -1 sodium trimethoxyborohydride Chemical compound 0.000 description 9
- 229960004046 apomorphine Drugs 0.000 description 7
- 230000000701 neuroleptic effect Effects 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- NALWAKMXVXNWCO-BTJKTKAUSA-N (z)-but-2-enedioic acid;1h-pyrrole Chemical compound C=1C=CNC=1.OC(=O)\C=C/C(O)=O NALWAKMXVXNWCO-BTJKTKAUSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000009194 climbing Effects 0.000 description 5
- LNFLVFXWOCZBMF-UHFFFAOYSA-N cyclohepta[c]pyrrole Chemical compound C1=CC=CC=C2C=NC=C21 LNFLVFXWOCZBMF-UHFFFAOYSA-N 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000001624 sedative effect Effects 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
- 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
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 229910010082 LiAlH Inorganic materials 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 230000037396 body weight Effects 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
- 125000000468 ketone group Chemical group 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229960004889 salicylic acid Drugs 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 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 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 230000000202 analgesic effect Effects 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
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
- 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 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
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 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 1
- NALWAKMXVXNWCO-WLHGVMLRSA-N (e)-but-2-enedioic acid;1h-pyrrole Chemical compound C=1C=CNC=1.OC(=O)\C=C\C(O)=O NALWAKMXVXNWCO-WLHGVMLRSA-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
- ILXCAPNAPIRSPT-UHFFFAOYSA-N 2H-cyclohepta[c]pyrrol-1-one Chemical compound O=C1C=2C(=CN1)C=CC=CC=2 ILXCAPNAPIRSPT-UHFFFAOYSA-N 0.000 description 1
- USQWMRQZYNJQCT-UHFFFAOYSA-N 2h-thiepino[4,5-c]pyrrole Chemical compound C1=CSC=CC2=CNC=C21 USQWMRQZYNJQCT-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
- 229910016455 AlBN Inorganic materials 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 238000006027 Birch reduction reaction Methods 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 238000006824 Eschweiler-Clarke methylation reaction Methods 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 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
- 150000007513 acids Chemical class 0.000 description 1
- 238000013019 agitation Methods 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
- 150000001412 amines Chemical class 0.000 description 1
- 150000003868 ammonium compounds Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
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- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 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
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- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- LMBQFLQKKMVTMV-UHFFFAOYSA-N cyclohepta[b]pyrrole Chemical compound C1=CC=CC2=NC=CC2=C1 LMBQFLQKKMVTMV-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003001 depressive 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
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000008187 granular material Substances 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
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
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- 230000036031 hyperthermia Effects 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- KPJPHPFMCOKUMW-UHFFFAOYSA-N iodomethane Chemical compound I[CH2] KPJPHPFMCOKUMW-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 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
- 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
- 239000007788 liquid Substances 0.000 description 1
- 229910001338 liquidmetal Inorganic materials 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- WVKNBCACIPKHEW-UHFFFAOYSA-N n,n-diethylethanamine;n,n-dimethylformamide Chemical compound CN(C)C=O.CCN(CC)CC WVKNBCACIPKHEW-UHFFFAOYSA-N 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
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 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
- 230000001681 protective effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 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
- QPPXNMSORVYMTG-UHFFFAOYSA-N pyrrolo[3,4-d]azepine Chemical compound C1=NC=C2C1=CC=NC=C2 QPPXNMSORVYMTG-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
- 150000003254 radicals Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 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
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 238000005303 weighing Methods 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)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI832085A FI67701C (fi) | 1976-05-24 | 1983-06-09 | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara tetracykliska foereningar |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL7605526 | 1976-05-24 | ||
| NL7605526A NL7605526A (nl) | 1976-05-24 | 1976-05-24 | Nieuwe tetracyclische derivaten. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI771635A7 FI771635A7 (en:Method) | 1977-11-25 |
| FI65238B FI65238B (fi) | 1983-12-30 |
| FI65238C true FI65238C (fi) | 1984-04-10 |
Family
ID=19826245
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI771635A FI65238C (fi) | 1976-05-24 | 1977-05-23 | Foerfarande foer framstaellning av terapeutiskt anvaendbara teracykliska foereningar |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4145434A (en:Method) |
| JP (2) | JPS532465A (en:Method) |
| AU (1) | AU509073B2 (en:Method) |
| BE (1) | BE854915A (en:Method) |
| CA (1) | CA1122976A (en:Method) |
| CH (2) | CH633536A5 (en:Method) |
| DE (2) | DE2723209A1 (en:Method) |
| DK (1) | DK157868C (en:Method) |
| ES (3) | ES459024A1 (en:Method) |
| FI (1) | FI65238C (en:Method) |
| FR (1) | FR2352800A1 (en:Method) |
| GB (1) | GB1567862A (en:Method) |
| HU (1) | HU173795B (en:Method) |
| IE (1) | IE45419B1 (en:Method) |
| LU (1) | LU77387A1 (en:Method) |
| NL (1) | NL7605526A (en:Method) |
| SE (1) | SE436202B (en:Method) |
| ZA (1) | ZA772752B (en:Method) |
Families Citing this family (87)
| 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 |
| DE3069086D1 (de) * | 1979-12-10 | 1984-10-04 | Ciba Geigy Ag | Azatetracyclic carbonitriles |
| 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 |
| IL68711A (en) * | 1982-05-18 | 1986-12-31 | Sparamedica Ag | Dihydro-8-halo-6-phenylpyrrolo-(3,4-d)(2)benzazepin derivatives,their preparation and pharmaceutical compositions containing them |
| JPS62101941U (en:Method) * | 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 |
| PT690863E (pt) * | 1993-04-06 | 2003-07-31 | Abbott Lab | Compostos tetraciclicos como agonistas da dopamina |
| PL180465B1 (pl) * | 1994-03-02 | 2001-02-28 | Akzo Nobel Nv | Kompozycja farmaceutyczna zawierajaca trans-5-chloro-2-metylo-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7]oksepino[4,5-c]pirol PL PL PL |
| 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 |
| HUP9901613A3 (en) * | 1996-04-12 | 2001-08-28 | Janssen Pharmaceutica Nv | Substituted tetracyclic fused furanamine derivatives, process for their preparation, use thereof and pharmaceutical compositions containing them |
| CA2290070A1 (en) * | 1997-05-26 | 1998-12-03 | 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 |
| KR20060011873A (ko) * | 2003-05-16 | 2006-02-03 | 화이자 프로덕츠 인코포레이티드 | 비정형 항정신약과 ｇａｂａ 조절제, 항경련성 약물 또는 벤조다이아제핀의 치료 혼합물 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| HRP20030959A2 (en:Method) * | 2003-11-21 | 2005-10-31 | Pliva-Istra�iva�ki institut d.o.o. | |
| 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 |
| CA2556160A1 (en) * | 2004-02-13 | 2005-09-01 | Pfizer Products Inc. | Therapeutic combinations of atypical antipsychotics with corticotropin releasing factor antagonists |
| EP1753460A2 (en) * | 2004-05-11 | 2007-02-21 | Pfizer Products Inc. | Combination of atypical antipsychotics and 5-ht1b receptor antagonists |
| BRPI0516000A (pt) * | 2004-10-15 | 2008-05-06 | Pfizer | uso de um composto ou de um sal, solvato, hidrato ou isÈmero óptico farmaceuticamente aceitável do mesmo, método para tratar distúrbio bipolar em um mamìfero em necessidade do mesmo, e, kit para uso no tratamento de distúrbios bipolares |
| 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 |
| UA93043C2 (ru) | 2005-04-07 | 2011-01-10 | Н.В. Органон | ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ ДЛЯ ПОЛУЧЕНИЯ ТРАНС-5-ХЛОР-2-МЕТИЛ-2,3,3А,12В-ТЕТРАГИДРО-1Н-ДИБЕНЗ[2,3:6,7]ОКСЕПИНО[4,5-с]ПИРОЛА |
| PL1917267T3 (pl) * | 2005-04-07 | 2009-06-30 | Merck Sharp & Dohme | Postać krystaliczna maleinianu asenapiny |
| 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 |
| US7750167B2 (en) * | 2006-07-05 | 2010-07-06 | N.V. Organon | Process for the preparation of asenapine and intermediate products used in said process |
| TW200817414A (en) * | 2006-07-05 | 2008-04-16 | Organon Nv | Process for the preparation of asenapine and intermediate products used in said process |
| PE20081457A1 (es) * | 2006-10-06 | 2008-10-18 | Organon Nv | Asenapina amorfa, procesos para prepararlas y su uso para tratar trastornos del sistema nervioso central |
| US7875729B2 (en) * | 2007-01-05 | 2011-01-25 | Synthon Bv | Process for making asenapine |
| EP2170399A1 (en) * | 2007-06-05 | 2010-04-07 | 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 |
| MX2010007404A (es) * | 2008-01-04 | 2010-10-05 | Organon Nv | Procedimiento para la preparacion de asenapina y productos intermediarios utilizados en dicho procedimiento. |
| EP2254420A4 (en) | 2008-02-20 | 2012-02-15 | Targia Pharmaceuticals | CNS PHARMACEUTICALS AND METHOD FOR THEIR USE |
| JP2011526881A (ja) * | 2008-06-25 | 2011-10-20 | ファイザー・インク | ジアリール化合物およびそれらの使用 |
| JP5801295B2 (ja) | 2009-06-24 | 2015-10-28 | メルク・シャープ・エンド・ドーム・ベー・フェー | アセナピンを含有する注射可能な配合物およびそれを用いた処置方法 |
| AR077429A1 (es) | 2009-07-29 | 2011-08-24 | Organon Nv | Compuestos hidroxiasenapina sus derivados y composiciones farmaceuticas que comprenden los mismos |
| CA2802990A1 (en) | 2010-06-18 | 2011-12-22 | Dr. Reddy's Laboratories Ltd. | Asenapine maleate |
| WO2012013766A1 (en) | 2010-07-29 | 2012-02-02 | Laboratorios Lesvi, S.L. | Novel process for the preparation of asenapine |
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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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| ES2575544T3 (es) | 2010-12-24 | 2016-06-29 | Medichem, S.A. | Procedimientos para la preparación de 5-cloro-2-metil-2,3,3a,12b-tetrahidro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pirrol |
| 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 |
| WO2012156676A1 (en) | 2011-05-18 | 2012-11-22 | Laboratorios Lesvi S.L. | Monoclinic crystalline form of asenapine maleate with a specific particle size distribution |
| JP6014656B2 (ja) | 2011-05-18 | 2016-10-25 | ラビラトリオス レスビ エス エレ | 化合物の多形体 |
| WO2013024492A2 (en) | 2011-07-01 | 2013-02-21 | Megafine Pharma (P) Ltd. | A process for the preparation of asenapine and novel salts thereof |
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| WO2013035109A1 (en) | 2011-09-08 | 2013-03-14 | Mylan Laboratories Ltd | Improved process for the preparation of asenapine maleate |
| WO2013041604A1 (en) | 2011-09-21 | 2013-03-28 | Sandoz Ag | Crystal form of asenapine maleate |
| EP2572703A1 (en) | 2011-09-21 | 2013-03-27 | Hexal AG | Compressed oral dosage form for asenapine maleate |
| AU2012346880A1 (en) | 2011-11-28 | 2014-06-19 | Sun Pharmaceutical Industries Limited | Process for the preparation of asenapine intermediate |
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| JP6440625B2 (ja) | 2012-11-14 | 2018-12-19 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 精神分裂病を処置するための方法および組成物 |
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| AU2016279052A1 (en) | 2015-06-19 | 2018-02-15 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
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| US20180170941A1 (en) | 2016-12-19 | 2018-06-21 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
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| WO2019246300A1 (en) | 2018-06-19 | 2019-12-26 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| BR112020026099A2 (pt) | 2018-06-20 | 2021-03-23 | Lts Lohmann Therapie-Systeme Ag | sistema terapêutico transdérmico que contém asenapina |
| EP3810099A1 (en) | 2018-06-20 | 2021-04-28 | LTS Lohmann Therapie-Systeme AG | Transdermal therapeutic system containing asenapine |
| CN110183457A (zh) * | 2019-06-27 | 2019-08-30 | 浙江天顺药业有限公司 | 一种阿塞那平及其制备方法 |
| CN112830931A (zh) | 2019-08-13 | 2021-05-25 | 浙江奥翔药业股份有限公司 | 制备阿塞那平的方法 |
| US11679407B2 (en) * | 2020-06-26 | 2023-06-20 | Intel Corporation | Liquid metal thermal interface material application |
| WO2023006954A1 (en) | 2021-07-30 | 2023-02-02 | Fundació Institut D'investigació Biomèdica De Bellvitge (Idibell) | Asenapine for use in cancer |
| JP2025529834A (ja) | 2022-08-19 | 2025-09-09 | エージンバイオ， インコーポレイテッド | 認知障害を処置するためのベンゾアゼピン誘導体、組成物および方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH507232A (de) * | 1968-11-27 | 1971-05-15 | 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 US US05/798,222 patent/US4145434A/en not_active Expired - Lifetime
- 1977-05-18 FR FR7715413A patent/FR2352800A1/fr active Granted
- 1977-05-20 CH CH626477A patent/CH633536A5/de not_active IP Right Cessation
- 1977-05-20 AU AU25331/77A patent/AU509073B2/en not_active Expired
- 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 DE DE19772723209 patent/DE2723209A1/de not_active Withdrawn
- 1977-05-23 HU HU77AO447A patent/HU173795B/hu unknown
- 1977-05-23 FI FI771635A patent/FI65238C/fi not_active IP Right Cessation
- 1977-05-23 LU LU77387A patent/LU77387A1/xx unknown
- 1977-05-23 BE BE177807A patent/BE854915A/xx not_active IP Right Cessation
- 1977-05-23 DE DE2760372A patent/DE2760372C2/de not_active Expired - Lifetime
- 1977-05-24 DK DK227477A patent/DK157868C/da not_active IP Right Cessation
- 1977-05-24 CA CA279,010A patent/CA1122976A/en not_active Expired
-
1978
- 1978-06-01 ES ES470408A patent/ES470408A1/es not_active Expired
- 1978-06-01 ES ES470407A patent/ES470407A1/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
Also Published As
| Publication number | Publication date |
|---|---|
| LU77387A1 (en:Method) | 1977-08-29 |
| ZA772752B (en) | 1978-04-26 |
| CH637382A5 (de) | 1983-07-29 |
| DE2760372C2 (en:Method) | 1991-05-29 |
| DE2723209A1 (de) | 1977-12-15 |
| DK157868B (da) | 1990-02-26 |
| HU173795B (hu) | 1979-08-28 |
| JPS6238348B2 (en:Method) | 1987-08-17 |
| JPS61178965A (ja) | 1986-08-11 |
| DK157868C (da) | 1990-07-30 |
| BE854915A (fr) | 1977-11-23 |
| SE436202B (sv) | 1984-11-19 |
| AU509073B2 (en) | 1980-04-17 |
| FI771635A7 (en:Method) | 1977-11-25 |
| JPS532465A (en) | 1978-01-11 |
| IE45419L (en) | 1977-11-24 |
| SE7705957L (sv) | 1977-11-25 |
| CH633536A5 (de) | 1982-12-15 |
| ES470408A1 (es) | 1979-01-01 |
| AU2533177A (en) | 1978-11-23 |
| FI65238B (fi) | 1983-12-30 |
| JPS6134426B2 (en:Method) | 1986-08-07 |
| FR2352800B1 (en:Method) | 1980-02-01 |
| NL7605526A (nl) | 1977-11-28 |
| FR2352800A1 (fr) | 1977-12-23 |
| GB1567862A (en) | 1980-05-21 |
| CA1122976A (en) | 1982-05-04 |
| US4145434A (en) | 1979-03-20 |
| DK227477A (da) | 1977-11-25 |
| ES470407A1 (es) | 1979-01-01 |
| IE45419B1 (en) | 1982-08-25 |
| ES459024A1 (es) | 1978-11-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired | ||
| MA | Patent expired |
Owner name: AKZO N.V. |