FI65238C - Foerfarande foer framstaellning av terapeutiskt anvaendbara teracykliska foereningar - Google Patents

Foerfarande foer framstaellning av terapeutiskt anvaendbara teracykliska foereningar Download PDF

Info

Publication number: FI65238C
Authority: FI; Finland
Prior art keywords: formula; compounds; alkyl; compound; test
Prior art date: 1976-05-24

Application number

FI771635A

Other languages

English (en)

Finnish (fi)

Other versions

FI771635A7 (fr

FI65238B (fi

Inventor

Willem Jacob Van Der Burg

Original Assignee

Akzo Nv

Priority date (The priority date 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 date listed.)

1976-05-24

Filing date

1977-05-23

Publication date

1984-04-10

1977-05-23 Application filed by Akzo Nv filed Critical Akzo Nv

1977-11-25 Publication of FI771635A7 publication Critical patent/FI771635A7/fi

1983-06-09 Priority to FI832085A priority Critical patent/FI67701C/fi

1983-12-30 Application granted granted Critical

1983-12-30 Publication of FI65238B publication Critical patent/FI65238B/fi

1984-04-10 Publication of FI65238C publication Critical patent/FI65238C/fi

Links

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
229940005513 antidepressants 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
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
239000002775 capsule Substances 0.000 description 1
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
239000000284 extract Substances 0.000 description 1
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
229940071870 hydroiodic acid Drugs 0.000 description 1
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)
Psychiatry (AREA)
Anesthesiology (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)

FI771635A 1976-05-24 1977-05-23 Foerfarande foer framstaellning av terapeutiskt anvaendbara teracykliska foereningar FI65238C (fi)

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 (fr)	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 (fr)
JP (2)	JPS532465A (fr)
AU (1)	AU509073B2 (fr)
BE (1)	BE854915A (fr)
CA (1)	CA1122976A (fr)
CH (2)	CH633536A5 (fr)
DE (2)	DE2760372C2 (fr)
DK (1)	DK157868C (fr)
ES (3)	ES459024A1 (fr)
FI (1)	FI65238C (fr)
FR (1)	FR2352800A1 (fr)
GB (1)	GB1567862A (fr)
HU (1)	HU173795B (fr)
IE (1)	IE45419B1 (fr)
LU (1)	LU77387A1 (fr)
NL (1)	NL7605526A (fr)
SE (1)	SE436202B (fr)
ZA (1)	ZA772752B (fr)

Families Citing this family (87)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0007450A1 (fr) *	1978-07-07	1980-02-06	Ciba-Geigy Ag	Carbonitriles azatétracycliques, leur préparation, compositions pharmaceutiques les contenant et leur application
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 (fr) *	1985-12-16	1987-06-29
IE62754B1 (en) *	1988-08-26	1995-02-22	Akzo Nv	Tetracyclic antidepressants
EP0569096A1 (fr) *	1992-05-08	1993-11-10	Akzo Nobel N.V.	Préparation de dépôt
DK0690863T3 (da) *	1993-04-06	2003-06-30	Abbott Lab	Tetracykliske forbindelser som dopamin-agonister
CN1079670C (zh) *	1994-03-02	2002-02-27	阿克佐诺贝尔公司	舌下或颊给药的药物组合物
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
DE69720709T2 (de) *	1996-04-12	2004-03-11	Janssen Pharmaceutica N.V.	Substituierte tetracyclische tetrahydrofuranderivate
WO1998054186A1 (fr) *	1997-05-26	1998-12-03	Akzo Nobel N.V.	Sels d'acides sulfoniques aromatiques
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
EP1633400A2 (fr) *	2003-05-16	2006-03-15	Pfizer Products Inc.	Combinaisons therapeutiques d'antipsychotiques atypiques avec des modulateurs de l'acide 4-aminobutanoique et/ou des medicaments anticonvulsivants
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
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
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
HRP20030959A2 (fr) *	2003-11-21	2005-10-31	Pliva-Istra�iva�ki institut d.o.o.
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
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
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
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
AU2005215257A1 (en) *	2004-02-13	2005-09-01	Pfizer Products Inc.	Therapeutic combinations of atypical antipsychotics with corticotropin releasing factor antagonists
EP1753460A2 (fr) *	2004-05-11	2007-02-21	Pfizer Products Inc.	Combinaison d'antipsychotiques atypiques et d'antagonistes du recepteur de 5-ht1b
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
CA2603181A1 (fr) *	2005-04-07	2006-10-12	N.V. Organon	Composes intermediaires pour la synthese du trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1h-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole
PL1710245T3 (pl) *	2005-04-07	2008-01-31	Merck Sharp & Dohme	Postać krystaliczna maleinianu asenapiny
US7741358B2 (en) *	2005-04-14	2010-06-22	N.V. Organon	Crystal form of asenapine maleate
WO2007046554A1 (fr) *	2005-10-21	2007-04-26	Sumitomo Chemical Company, Limited	Procédé pour la production d'un composé de dibenzoxépinopyrrole, intermédiaire pour la production du composé et procédé pour la production de l'intermédiaire
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
TW200831514A (en) *	2006-10-06	2008-08-01	Organon Nv	Amorphous asenapine and processes for preparing same
US7875729B2 (en) *	2007-01-05	2011-01-25	Synthon Bv	Process for making asenapine
WO2008148515A1 (fr) *	2007-06-05	2008-12-11	Synthon B.V.	Administration intranasale d'asénapine et compositions à cet usage
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
JP2011508751A (ja) *	2008-01-04	2011-03-17	ナームローゼ・フエンノートチヤツプ・オルガノン	アセナピンの調製方法および前記方法において使用される中間生成物
EP2254420A4 (fr)	2008-02-20	2012-02-15	Targia Pharmaceuticals	Compositions pharmaceutiques actives sur le snc et méthodes d'utilisation
EP2321011A1 (fr) *	2008-06-25	2011-05-18	Pfizer Inc.	Composés diaryle et leurs utilisations
MX2012000061A (es) *	2009-06-24	2012-06-01	Msd Oss Bv	Formulaciones inyectables que contienen asenapina, y metodo de tratamiento usando las mismas.
AR077429A1 (es)	2009-07-29	2011-08-24	Organon Nv	Compuestos hidroxiasenapina sus derivados y composiciones farmaceuticas que comprenden los mismos
WO2011159903A2 (fr)	2010-06-18	2011-12-22	Dr. Reddy's Laboratories Ltd.	Maléate d'asénapine
WO2012013766A1 (fr)	2010-07-29	2012-02-02	Laboratorios Lesvi, S.L.	Nouveau procédé de synthèse de l'asénapine
DK3034079T3 (en)	2010-11-15	2018-02-05	Agenebio Inc	PYRIDAZINE DERIVATIVES, COMPOSITIONS AND PROCEDURES FOR TREATING COGNITIVE WEAKNESS
WO2012066565A2 (fr)	2010-11-16	2012-05-24	Cadila Healthcare Limited	Maléate d'asénapine amorphe et forme cristalline et procédé pour leur préparation
EP2468750A1 (fr)	2010-12-13	2012-06-27	Chemo Ibérica, S.A.	Formes polymorphiques de maléate d'asénapine et procédés de préparation
EP2468751B1 (fr)	2010-12-24	2016-03-16	Medichem, S.A.	Procédé de préparation de 5-chloro-2-méthyl-2,3,3a,12b-tétrahydro-1H-dibenzo[2,3:6,7]oxépino[4,5-c]pyrrole
WO2012123325A1 (fr)	2011-03-11	2012-09-20	Medichem S.A.	Nouvelles formes cristallines du sel de trans-5-chloro-2-méthyl-2,3,3a,12b-tétrahydro-1h-dibenzo[2,3:6,7] oxépino[4,5-c]pyrrole avec l'acide maléique
ITMI20110734A1 (it)	2011-05-02	2012-11-03	Olon Spa	Sali cristallini di asenapina
EP2524919A1 (fr)	2011-05-17	2012-11-21	Sandoz AG	Nouveaux sels cristallins d'asénapine avec des di-acides et des tri-acides cristallins
EP2524921A1 (fr) *	2011-05-17	2012-11-21	Sandoz AG	Nouveaux sels cristallins d'asénapine
EP2709615A1 (fr)	2011-05-18	2014-03-26	Laboratorios Lesvi, S.L.	Forme cristalline monoclinique de maléate d'asénapine présentant une granulométrie spécifique
US9505771B2 (en)	2011-05-18	2016-11-29	Laboratories Lesvi S.L.	Stable micronised monoclin form of asenapine maleate and its synthesis
WO2013024492A2 (fr)	2011-07-01	2013-02-21	Megafine Pharma (P) Ltd.	Procédé de préparation d'asénapine et nouveaux sels de celle-ci
WO2013011461A1 (fr)	2011-07-20	2013-01-24	Ranbaxy Laboratories Limited	Procédé de préparation de maléate d'asénapine
WO2013035109A1 (fr)	2011-09-08	2013-03-14	Mylan Laboratories Ltd	Procédé amélioré de préparation de maléate d'asénapine
EP2572703A1 (fr)	2011-09-21	2013-03-27	Hexal AG	Forme pharmaceutique orale compressée pour maléate d'asénapine
WO2013041604A1 (fr)	2011-09-21	2013-03-28	Sandoz Ag	Forme cristalline de maléate d'asénapine
US20140336391A1 (en)	2011-11-28	2014-11-13	Ranbaxy Laboratories Limited	Process for the preparation of asenapine intermediate
CN103254201B (zh) *	2012-02-21	2016-04-13	四川科伦药物研究有限公司	一种阿塞那平的制备方法
WO2013190481A1 (fr) *	2012-06-21	2013-12-27	Alembic Pharmaceuticals Limited	Procédé pour la préparation d'asénapine et sels d'intermédiaires de celle-ci
ITMI20121810A1 (it)	2012-10-24	2014-04-25	Chemo Iberica Sa	Poliformi di maleato di asenapina e processo per la loro preparazione
WO2014078568A1 (fr)	2012-11-14	2014-05-22	The Johns Hopkins University	Méthodes et compositions pour le traitement de la schizophrénie
WO2014127786A1 (fr)	2013-02-22	2014-08-28	Zentiva, K.S.	Composition pharmaceutique à désintégration orale comprenant de l'asénapine
CN103113379A (zh) *	2013-03-12	2013-05-22	盛世泰科生物医药技术(苏州)有限公司	阿塞那平马来酸盐的合成工艺
CN103351393B (zh) *	2013-07-03	2016-04-06	华裕(无锡)制药有限公司	用于制备阿森那平之还原剂及阿森那平之制备方法
CN112409363B (zh)	2013-12-20	2023-11-14	艾吉因生物股份有限公司	用于治疗认知损害的苯并二氮杂䓬衍生物、组合物和方法
CN103772401A (zh) *	2014-01-07	2014-05-07	万特制药(海南)有限公司	11-氯-2,3,3a,12b-四氢-2-甲基-1H-二苯并[2,3:6,7]氧杂卓并[4,5-c]吡咯-1-酮的一种新精制方法
CN103772400A (zh) *	2014-01-07	2014-05-07	万特制药(海南)有限公司	反式-5-氯-2,3,3a,12b-四氢-1H-二苯并[2,3:6,7]氧杂卓并[4,5-c]吡咯的制备方法
WO2016198113A1 (fr)	2015-06-11	2016-12-15	Alrise Biosystems Gmbh	Procédé pour la préparation de microparticules chargées de médicament
WO2016205739A1 (fr)	2015-06-19	2016-12-22	Belew Mekonnen	Dérivés de benzodiazépine, compositions et méthodes de traitement de la déficience cognitive
US20180170941A1 (en)	2016-12-19	2018-06-21	Agenebio, Inc.	Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
US11505555B2 (en)	2016-12-19	2022-11-22	Agenebio, Inc.	Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
PL3338768T3 (pl)	2016-12-20	2020-05-18	Lts Lohmann Therapie-Systeme Ag	Transdermalny system terapeutyczny zawierający asenapinę
ES3001152T3 (es)	2016-12-20	2025-03-04	Lts Lohmann Therapie Systeme Ag	Sistema terapéutico transdérmico que contiene asenapina y polisiloxano o poliisobutileno
WO2019002204A1 (fr)	2017-06-26	2019-01-03	Lts Lohmann Therapie-Systeme Ag	Système thérapeutique transdermique contenant de l'asénapine et un polymère hybride acrylique de type silicone
BR112020026062B1 (pt)	2018-06-19	2023-04-04	Agenebio, Inc	Compostos derivados de benzodiazepina ou um sal farmaceuticamente aceitavel, isômero ou combinação dos mesmos, composição farmacêutica compreendendo os mesmos e usos dos mesmos para o tratamento de comprometimento cognitivo, câncer cerebral e psicose da doença de parkinson
AU2019291060B2 (en)	2018-06-20	2024-09-05	Lts Lohmann Therapie-Systeme Ag	Transdermal therapeutic system containing asenapine
EP3810099A1 (fr)	2018-06-20	2021-04-28	LTS Lohmann Therapie-Systeme AG	Système thérapeutique transdermique comportant de l'asénapine
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 (fr)	2021-07-30	2023-02-02	Fundació Institut D'investigació Biomèdica De Bellvitge (Idibell)	Asénapine pour une utilisation dans le cancer
US20240132513A1 (en)	2022-08-19	2024-04-25	Agenebio, Inc.	Benzazepine derivatives, compositions, and methods for treating cognitive impairment

Family Cites Families (3)

* Cited by examiner, † Cited by third party
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 US US05/798,222 patent/US4145434A/en not_active Expired - Lifetime
- 1977-05-18 FR FR7715413A patent/FR2352800A1/fr active Granted
- 1977-05-20 SE SE7705957A patent/SE436202B/xx 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 CH CH626477A patent/CH633536A5/de not_active IP Right Cessation
- 1977-05-21 ES ES459024A patent/ES459024A1/es not_active Expired
- 1977-05-23 LU LU77387A patent/LU77387A1/xx unknown
- 1977-05-23 HU HU77AO447A patent/HU173795B/hu unknown
- 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 BE BE177807A patent/BE854915A/fr not_active IP Right Cessation
- 1977-05-23 DE DE19772723209 patent/DE2723209A1/de not_active Withdrawn
- 1977-05-24 CA CA279,010A patent/CA1122976A/fr 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

Also Published As

Publication number	Publication date
IE45419L (en)	1977-11-24
AU509073B2 (en)	1980-04-17
CA1122976A (fr)	1982-05-04
DK157868C (da)	1990-07-30
FI771635A7 (fr)	1977-11-25
US4145434A (en)	1979-03-20
SE436202B (sv)	1984-11-19
ES459024A1 (es)	1978-11-01
DK227477A (da)	1977-11-25
GB1567862A (en)	1980-05-21
BE854915A (fr)	1977-11-23
IE45419B1 (en)	1982-08-25
FR2352800B1 (fr)	1980-02-01
NL7605526A (nl)	1977-11-28
CH633536A5 (de)	1982-12-15
JPS6238348B2 (fr)	1987-08-17
LU77387A1 (fr)	1977-08-29
JPS61178965A (ja)	1986-08-11
JPS6134426B2 (fr)	1986-08-07
HU173795B (hu)	1979-08-28
FI65238B (fi)	1983-12-30
DE2723209A1 (de)	1977-12-15
JPS532465A (en)	1978-01-11
DE2760372C2 (fr)	1991-05-29
ES470408A1 (es)	1979-01-01
ES470407A1 (es)	1979-01-01
CH637382A5 (de)	1983-07-29
SE7705957L (sv)	1977-11-25
FR2352800A1 (fr)	1977-12-23
AU2533177A (en)	1978-11-23
DK157868B (da)	1990-02-26
ZA772752B (en)	1978-04-26

Legal Events

Date	Code	Title	Description
1977-05-23	MA	Patent expired
2004-08-31	MA	Patent expired	Owner name: AKZO N.V.

Publication	Publication Date	Title
FI65238B (fi)	1983-12-30	Foerfarande foer framstaellning av terapeutiskt anvaendbara teracykliska foereningar
KR20060072142A (ko)	2006-06-27	Ｃｒｆ 길항제 및 이환식 복소환 화합물
EP0508549A2 (fr)	1992-10-14	Nouveaux dérivés de la triazolopyrimidine et de la pyrazolopyrimidine utilés pour traîter la cachexie
PL190960B1 (pl)	2006-02-28	Tetracykliczna pochodna tetrahydrofuranu, kompozycja farmaceutyczna i sposób wytwarzania tetracyklicznej pochodnej tetrahydrofuranu
CA1262908A (fr)	1989-11-14	Pyrrolobenzimidazoles, procede de preparation et composes pharmaceutiques les contenant
FR2799757A1 (fr)	2001-04-20	Nouveaux derives polycycliques azaindoliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US4271179A (en)	1981-06-02	1,2,3,3a,8,12b-Hexahydro-dibenzo[1,2;5,6]cyclohepta[3,4-C]pyrroles and pharmaceutical use thereof
RU95104939A (ru)	1996-10-27	Тетрациклические соединения, способ их получения и промежуточные соединения для этого и применение их в качестве противоопухолевых веществ
US3993650A (en)	1976-11-23	Pyrrolo [3,4-d] pyrimidines
US4158059A (en)	1979-06-12	Tension reducing 2,3,4,4a,9,136-hexahydro-dibenz[1,2;5,6]cyclohepta[3,4-c]py
US4406900A (en)	1983-09-27	Neuroleptic use of morphanthridines
NO763567L (fr)	1977-04-26
CA1271193A (fr)	1990-07-03	Diazepinoindoles, leur fabrication et compositions pharmaceutiques les renfermant
CA1136134A (fr)	1982-11-23	1-hydroxyalcanamine tetrahydrocarbazoles
US4271177A (en)	1981-06-02	2,3,3a,12b-Tetrahydro-1H-dibenzo[2,3;6,7]thiepino[4,5-c]pyrroles and pharmaceutical use thereof
FI67701B (fi)	1985-01-31	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara tetracykliska foereningar
US4271178A (en)	1981-06-02	1,2,3,3a,8,12b-Hexahydro-dibenzo[b,f]pyrrolo[3,4-d]azepines and pharmaceutical use thereof
US4177275A (en)	1979-12-04	Tension reducing 2,3,4,4a,9,13b-hexahydro-1H-dibenzo[b,f]pyrido[3,4-d]azepine derivatives
US4224321A (en)	1980-09-23	Biologically active tetracyclic compounds and pharmaceutical compositions containing same
US4548947A (en)	1985-10-22	1-(Substituted-aryl)-dihydro-1H-pyrrolizine-3,5-[2H,6H-]diones and use for reversing amnesia
RICE et al.	1958	Hypotensive Agents. IX. 3-Azabicyclo [3.3. 1] nonane Derivatives1
CA1045135A (fr)	1978-12-26	Pyrrolo (3,4-d) pyrimidines
US3458578A (en)	1969-07-29	Aminodibenzocycloalkenones
CA1271754A (fr)	1990-07-17	Derives de 1,5-benzoxathiepine; preparation et utilisation
AU690090C (en)	1999-07-29	Pyrrolopyrimidines as CRF antagonists