IL125480A - History 2, 3 - Benzodiazepine tricyclics with multiple transducers, pharmaceutical preparations containing them and processes for their preparation - Google Patents

History 2, 3 - Benzodiazepine tricyclics with multiple transducers, pharmaceutical preparations containing them and processes for their preparation

Info

Publication number: IL125480A
Authority: IL; Israel
Prior art keywords: benzodiazepine; llh; imidazo; dioxolo; methoxy
Prior art date: 1996-02-01

Application number

IL12548097A

Other languages

English (en)

Hebrew (he)

Other versions

IL125480A0 (en

Original Assignee

Schering Ag

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.)

1996-02-01

Filing date

1997-01-29

Publication date

2002-07-25

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=7785064&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IL125480(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1997-01-29 Application filed by Schering Ag filed Critical Schering Ag

1999-03-12 Publication of IL125480A0 publication Critical patent/IL125480A0/xx

2002-07-25 Publication of IL125480A publication Critical patent/IL125480A/en

Links

RPBDCDQMCRHNLM-UHFFFAOYSA-N C1=NNC=C2C=CC=CC2=C1 Chemical class C1=NNC=C2C=CC=CC2=C1 RPBDCDQMCRHNLM-UHFFFAOYSA-N 0.000 title claims description 74
238000000034 method Methods 0.000 title claims description 16
238000004519 manufacturing process Methods 0.000 title claims description 11
239000008194 pharmaceutical composition Substances 0.000 title claims 5
150000001875 compounds Chemical class 0.000 claims abstract description 140
-1 hydroxy, thiocyanato Chemical group 0.000 claims abstract description 59
229910052736 halogen Inorganic materials 0.000 claims abstract description 30
150000002367 halogens Chemical class 0.000 claims abstract description 29
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
239000001257 hydrogen Substances 0.000 claims abstract description 19
150000003839 salts Chemical class 0.000 claims abstract description 16
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 15
150000002431 hydrogen Chemical class 0.000 claims abstract description 13
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 11
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 8
125000004423 acyloxy group Chemical group 0.000 claims abstract description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 5
229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
239000001301 oxygen Substances 0.000 claims abstract description 5
229920006395 saturated elastomer Polymers 0.000 claims abstract description 5
229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
239000011593 sulfur Substances 0.000 claims abstract description 5
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 3
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 3
125000002252 acyl group Chemical group 0.000 claims abstract 4
125000004430 oxygen atom Chemical group O* 0.000 claims abstract 2
229940049706 benzodiazepine Drugs 0.000 claims description 54
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 46
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 32
238000006243 chemical reaction Methods 0.000 claims description 31
125000000217 alkyl group Chemical group 0.000 claims description 23
230000002829 reductive effect Effects 0.000 claims description 22
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 18
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 15
JENALEDAZIFLGS-UHFFFAOYSA-N 3h-imidazo[1,2-c][2,3]benzodiazepine Chemical compound C1=NN2CC=NC2=CC2=CC=CC=C21 JENALEDAZIFLGS-UHFFFAOYSA-N 0.000 claims description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
UWAHBPUHTZEWOC-UHFFFAOYSA-N 3H-[1,2,4]triazolo[4,3-c][2,3]benzodiazepine Chemical compound N1=NCN2N=CC3=C(C=C21)C=CC=C3 UWAHBPUHTZEWOC-UHFFFAOYSA-N 0.000 claims description 11
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 10
201000010099 disease Diseases 0.000 claims description 10
238000011282 treatment Methods 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
102000003678 AMPA Receptors Human genes 0.000 claims description 7
108090000078 AMPA Receptors Proteins 0.000 claims description 7
125000003277 amino group Chemical group 0.000 claims description 7
239000008177 pharmaceutical agent Substances 0.000 claims description 7
150000008065 acid anhydrides Chemical class 0.000 claims description 6
239000004480 active ingredient Substances 0.000 claims description 6
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 5
125000004414 alkyl thio group Chemical group 0.000 claims description 4
229910021529 ammonia Inorganic materials 0.000 claims description 4
LRJRPHROCLHMHK-UHFFFAOYSA-N boron;n,n-dimethylmethanamine Chemical compound [B].CN(C)C LRJRPHROCLHMHK-UHFFFAOYSA-N 0.000 claims description 4
239000003257 excitatory amino acid Substances 0.000 claims description 4
230000002461 excitatory amino acid Effects 0.000 claims description 4
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
208000024827 Alzheimer disease Diseases 0.000 claims description 3
125000000304 alkynyl group Chemical group 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
229910000365 copper sulfate Inorganic materials 0.000 claims description 3
ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 3
229940042795 hydrazides for tuberculosis treatment Drugs 0.000 claims description 3
208000013403 hyperactivity Diseases 0.000 claims description 3
UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 3
208000018737 Parkinson disease Diseases 0.000 claims description 2
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
208000015122 neurodegenerative disease Diseases 0.000 claims description 2
229910052720 vanadium Inorganic materials 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
230000004770 neurodegeneration Effects 0.000 claims 1
125000005017 substituted alkenyl group Chemical group 0.000 claims 1
125000004001 thioalkyl group Chemical group 0.000 claims 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 5
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract description 3
125000006700 (C1-C6) alkylthio group Chemical group 0.000 abstract description 3
125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
208000015114 central nervous system disease Diseases 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 160
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 138
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
238000002844 melting Methods 0.000 description 87
230000008018 melting Effects 0.000 description 87
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
239000000243 solution Substances 0.000 description 51
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
238000001704 evaporation Methods 0.000 description 41
230000008020 evaporation Effects 0.000 description 41
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 38
239000000203 mixture Substances 0.000 description 38
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
239000000741 silica gel Substances 0.000 description 27
229910002027 silica gel Inorganic materials 0.000 description 27
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 26
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
239000000047 product Substances 0.000 description 22
238000000354 decomposition reaction Methods 0.000 description 21
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
150000002828 nitro derivatives Chemical class 0.000 description 19
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
238000009835 boiling Methods 0.000 description 16
239000002904 solvent Substances 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
235000002639 sodium chloride Nutrition 0.000 description 15
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
229960000583 acetic acid Drugs 0.000 description 14
239000012043 crude product Substances 0.000 description 14
238000004440 column chromatography Methods 0.000 description 13
239000012074 organic phase Substances 0.000 description 13
239000002244 precipitate Substances 0.000 description 12
238000001953 recrystallisation Methods 0.000 description 12
239000000725 suspension Substances 0.000 description 12
UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 11
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
238000001816 cooling Methods 0.000 description 10
239000000706 filtrate Substances 0.000 description 10
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
239000003054 catalyst Substances 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
WZUODJNEIXSNEU-UHFFFAOYSA-N 2-Hydroxy-4-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(O)=C1 WZUODJNEIXSNEU-UHFFFAOYSA-N 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
229910000029 sodium carbonate Inorganic materials 0.000 description 7
239000007858 starting material Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
206010010904 Convulsion Diseases 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
239000012362 glacial acetic acid Substances 0.000 description 6
239000013067 intermediate product Substances 0.000 description 6
229910052740 iodine Inorganic materials 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
SUMMWKHSCFGUEV-UHFFFAOYSA-N 2,3-benzodiazepine-8-thione Chemical compound C1=NN=CC=C2C1=CC(C=C2)=S SUMMWKHSCFGUEV-UHFFFAOYSA-N 0.000 description 5
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 5
229910052786 argon Inorganic materials 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000005457 ice water Substances 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
239000007787 solid Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
FMSJHWUIRRQXMH-UHFFFAOYSA-N 3H-imidazo[1,5-c][2,3]benzodiazepine Chemical compound C1=NCN2N=CC3=C(C=C21)C=CC=C3 FMSJHWUIRRQXMH-UHFFFAOYSA-N 0.000 description 4
XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 description 4
ZCPGZXDGDWHJCS-UHFFFAOYSA-N 8-methoxy-1-(4-nitrophenyl)-3,5-dihydro-2,3-benzodiazepine-4-thione Chemical compound C12=CC(OC)=CC=C2CC(=S)NN=C1C1=CC=C([N+]([O-])=O)C=C1 ZCPGZXDGDWHJCS-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
241001061127 Thione Species 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
125000003342 alkenyl group Chemical group 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 4
239000012954 diazonium Substances 0.000 description 4
238000001035 drying Methods 0.000 description 4
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 4
239000012071 phase Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000006722 reduction reaction Methods 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
239000003826 tablet Substances 0.000 description 4
238000005406 washing Methods 0.000 description 4
QSDBXXXZPYVJOT-UHFFFAOYSA-N 1,2-benzodiazepin-8-one Chemical compound N1=NC=CC=C2C1=CC(C=C2)=O QSDBXXXZPYVJOT-UHFFFAOYSA-N 0.000 description 3
ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical class CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 3
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
RQKDTQACQPHOQL-UHFFFAOYSA-N 3h-2,3-benzodiazepine Chemical compound C1=NNC=CC2=CC=CC=C21 RQKDTQACQPHOQL-UHFFFAOYSA-N 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 3
QOONNGCBOZCBLS-UHFFFAOYSA-N 4-methoxy-2-(4-nitrobenzoyl)benzaldehyde Chemical compound COC1=CC=C(C=O)C(C(=O)C=2C=CC(=CC=2)[N+]([O-])=O)=C1 QOONNGCBOZCBLS-UHFFFAOYSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
ATDCFPVIRWVWQS-UHFFFAOYSA-N 8-methoxy-1-(4-nitrophenyl)-3,5-dihydro-2,3-benzodiazepin-4-one Chemical compound C12=CC(OC)=CC=C2CC(=O)NN=C1C1=CC=C([N+]([O-])=O)C=C1 ATDCFPVIRWVWQS-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
ZJEHXSSAXVIPJF-UHFFFAOYSA-N [5-(4-nitrophenyl)-9h-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-8-yl]methanol Chemical compound C12=CC=3OCOC=3C=C2CC(CO)=NN=C1C1=CC=C([N+]([O-])=O)C=C1 ZJEHXSSAXVIPJF-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
230000010933 acylation Effects 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
125000003118 aryl group Chemical group 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
125000001589 carboacyl group Chemical group 0.000 description 3
239000003638 chemical reducing agent Substances 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
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
150000001989 diazonium salts Chemical class 0.000 description 3
235000019253 formic acid Nutrition 0.000 description 3
150000008282 halocarbons Chemical class 0.000 description 3
239000011630 iodine Substances 0.000 description 3
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239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
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 1
ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
MRXQMNWIADOAJY-UHFFFAOYSA-M tetrabutylazanium;fluoride;dihydrofluoride Chemical compound F.F.[F-].CCCC[N+](CCCC)(CCCC)CCCC MRXQMNWIADOAJY-UHFFFAOYSA-M 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
150000004654 triazenes Chemical class 0.000 description 1
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- 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
- 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
- A61P25/06—Antimigraine agents
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- 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
- A61P25/22—Anxiolytics
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Psychiatry (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Psychology (AREA)
Pain & Pain Management (AREA)
Vascular Medicine (AREA)
Addiction (AREA)
Urology & Nephrology (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)

IL12548097A 1996-02-01 1997-01-29 History 2, 3 - Benzodiazepine tricyclics with multiple transducers, pharmaceutical preparations containing them and processes for their preparation IL125480A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19604919A DE19604919A1 (de)	1996-02-01	1996-02-01	Neue 2,3-Benzodiazepinderivate, deren Herstellung und Verwendung als Arzneimittel
PCT/DE1997/000234 WO1997028163A1 (de)	1996-02-01	1997-01-29	Kondensierte 2,3-benzodiazepin derivate und deren verwendung als ampa-rezeptoren-hemmer

Publications (2)

Publication Number	Publication Date
IL125480A0 IL125480A0 (en)	1999-03-12
IL125480A true IL125480A (en)	2002-07-25

Family

ID=7785064

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL12548097A IL125480A (en)	1996-02-01	1997-01-29	History 2, 3 - Benzodiazepine tricyclics with multiple transducers, pharmaceutical preparations containing them and processes for their preparation

Country Status (31)

Country	Link
US (2)	US6323197B1 (da)
EP (1)	EP0888356B1 (da)
JP (1)	JP4141499B2 (da)
KR (1)	KR100465269B1 (da)
CN (1)	CN1096464C (da)
AT (1)	ATE214703T1 (da)
AU (1)	AU724956B2 (da)
BG (1)	BG63394B1 (da)
BR (1)	BR9707335A (da)
CA (1)	CA2245539C (da)
CZ (1)	CZ289658B6 (da)
DE (2)	DE19604919A1 (da)
DK (1)	DK0888356T3 (da)
EE (1)	EE04017B1 (da)
ES (1)	ES2173435T3 (da)
HK (1)	HK1018782A1 (da)
HU (1)	HU224636B1 (da)
IL (1)	IL125480A (da)
IS (1)	IS2103B (da)
MY (1)	MY119140A (da)
NO (1)	NO983510L (da)
NZ (1)	NZ331187A (da)
PL (1)	PL187128B1 (da)
PT (1)	PT888356E (da)
RU (1)	RU2179557C2 (da)
SK (1)	SK283563B6 (da)
TR (1)	TR199801485T2 (da)
TW (1)	TW438801B (da)
UA (1)	UA56157C2 (da)
WO (1)	WO1997028163A1 (da)
ZA (1)	ZA97848B (da)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HUP9701325A1 (hu) *	1997-07-31	2000-08-28	Gyógyszerkutató Intézet Kft.	Új 2,3-benzodiazepin-származékok
UA67749C2 (uk) *	1997-08-12	2004-07-15	Егіш Дьйодьсердьяр Рт.	Похідна 8-заміщеного-9н-1,3-діоксол/4,5-h//2,3/бензодіазепіну з властивостями амра/каїнатного антагоніста, спосіб одержання похідних, фармацевтична композиція (варіанти), спосіб її одержання та спосіб лікування
WO2000001376A2 (en) *	1998-07-02	2000-01-13	Eisai Co., Ltd	Pharmaceutical compositions and their uses for treatment of demyelinating disorders
EP1296960A2 (en) *	2000-06-16	2003-04-02	Annovis, Inc.	5h-2,3-benzodiazepine antagonists of excitatory amino acid receptors
DE10041671C1 (de) *	2000-08-10	2002-06-13	Schering Ag	Verfahren zur Herstellung von Imidazo[1,2-c][2,3]benzodiazepinen sowie Phenylessigsäureester und Oxazol-Derivate als Zwischenprodukte bei deren Herstellung
US20070280876A1 (en) *	2004-03-25	2007-12-06	William Marsh Rice University	Functionalization of Carbon Nanotubes in Acidic Media
US20060166969A1 (en) *	2005-01-14	2006-07-27	Turski Lechoslaw A	AMPA antagonists for the treatment of dizziness, including vertigo and Meniere's disorder
EP2338492A1 (en)	2009-12-24	2011-06-29	Universidad del Pais Vasco	Methods and compositions for the treatment of alzheimer

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5891871A (en)	1996-03-21	1999-04-06	Cocensys, Inc.	Substituted 2,3-benzodiazepin-4-ones and the use thereof
HU9600871D0 (en) *	1996-04-04	1996-05-28	Gyogyszerkutato Intezet	New 2,3-benzodiazepine derivatives

1996
- 1996-02-01 DE DE19604919A patent/DE19604919A1/de not_active Withdrawn
1997
- 1997-01-29 UA UA98084653A patent/UA56157C2/uk unknown
- 1997-01-29 CN CN97192012A patent/CN1096464C/zh not_active Expired - Fee Related
- 1997-01-29 JP JP52724897A patent/JP4141499B2/ja not_active Expired - Fee Related
- 1997-01-29 EE EE9800225A patent/EE04017B1/xx not_active IP Right Cessation
- 1997-01-29 ES ES97916315T patent/ES2173435T3/es not_active Expired - Lifetime
- 1997-01-29 CZ CZ19982427A patent/CZ289658B6/cs not_active IP Right Cessation
- 1997-01-29 TR TR1998/01485T patent/TR199801485T2/xx unknown
- 1997-01-29 SK SK1033-98A patent/SK283563B6/sk unknown
- 1997-01-29 WO PCT/DE1997/000234 patent/WO1997028163A1/de active IP Right Grant
- 1997-01-29 RU RU98116292/04A patent/RU2179557C2/ru not_active IP Right Cessation
- 1997-01-29 AT AT97916315T patent/ATE214703T1/de not_active IP Right Cessation
- 1997-01-29 NZ NZ331187A patent/NZ331187A/xx unknown
- 1997-01-29 HU HU9901417A patent/HU224636B1/hu not_active IP Right Cessation
- 1997-01-29 BR BR9707335A patent/BR9707335A/pt not_active IP Right Cessation
- 1997-01-29 KR KR10-1998-0705917A patent/KR100465269B1/ko not_active IP Right Cessation
- 1997-01-29 DE DE59706686T patent/DE59706686D1/de not_active Expired - Lifetime
- 1997-01-29 CA CA002245539A patent/CA2245539C/en not_active Expired - Fee Related
- 1997-01-29 IL IL12548097A patent/IL125480A/en not_active IP Right Cessation
- 1997-01-29 AU AU25029/97A patent/AU724956B2/en not_active Ceased
- 1997-01-29 PL PL97328224A patent/PL187128B1/pl not_active IP Right Cessation
- 1997-01-29 DK DK97916315T patent/DK0888356T3/da active
- 1997-01-29 US US09/117,508 patent/US6323197B1/en not_active Expired - Fee Related
- 1997-01-29 PT PT97916315T patent/PT888356E/pt unknown
- 1997-01-29 EP EP97916315A patent/EP0888356B1/de not_active Expired - Lifetime
- 1997-01-31 MY MYPI97000379A patent/MY119140A/en unknown
- 1997-01-31 ZA ZA9700848A patent/ZA97848B/xx unknown
- 1997-02-01 TW TW086101218A patent/TW438801B/zh not_active IP Right Cessation
1998
- 1998-07-06 IS IS4794A patent/IS2103B/is unknown
- 1998-07-29 BG BG102658A patent/BG63394B1/bg unknown
- 1998-07-30 NO NO983510A patent/NO983510L/no unknown
1999
- 1999-09-02 HK HK99103802A patent/HK1018782A1/xx not_active IP Right Cessation
2001
- 2001-11-27 US US09/993,646 patent/US6600036B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2245539A1 (en)	1997-08-07
EE9800225A (et)	1998-12-15
US6323197B1 (en)	2001-11-27
BR9707335A (pt)	1999-07-20
CN1210538A (zh)	1999-03-10
UA56157C2 (uk)	2003-05-15
HK1018782A1 (en)	2000-01-07
EP0888356B1 (de)	2002-03-20
EP0888356A1 (de)	1999-01-07
ATE214703T1 (de)	2002-04-15
JP2000503997A (ja)	2000-04-04
DK0888356T3 (da)	2002-06-03
CZ242798A3 (cs)	1999-01-13
NZ331187A (en)	2000-01-28
AU724956B2 (en)	2000-10-05
ES2173435T3 (es)	2002-10-16
NO983510L (no)	1998-09-30
DE19604919A1 (de)	1997-08-07
NO983510D0 (no)	1998-07-30
ZA97848B (en)	1997-08-04
HU224636B1 (hu)	2005-12-28
IS4794A (is)	1998-07-06
US6600036B2 (en)	2003-07-29
PL328224A1 (en)	1999-01-18
DE59706686D1 (de)	2002-04-25
IL125480A0 (en)	1999-03-12
CN1096464C (zh)	2002-12-18
HUP9901417A3 (en)	2001-11-28
US20020052364A1 (en)	2002-05-02
TW438801B (en)	2001-06-07
PT888356E (pt)	2002-09-30
RU2179557C2 (ru)	2002-02-20
IS2103B (is)	2006-05-15
MY119140A (en)	2005-04-30
TR199801485T2 (xx)	1998-10-21
SK103398A3 (en)	1999-01-11
HUP9901417A2 (hu)	1999-08-30
SK283563B6 (sk)	2003-09-11
JP4141499B2 (ja)	2008-08-27
AU2502997A (en)	1997-08-22
BG102658A (en)	1999-06-30
PL187128B1 (pl)	2004-05-31
WO1997028163A1 (de)	1997-08-07
CZ289658B6 (cs)	2002-03-13
CA2245539C (en)	2005-10-04
KR100465269B1 (ko)	2005-04-14
BG63394B1 (bg)	2001-12-29
KR19990082192A (ko)	1999-11-25
EE04017B1 (et)	2003-04-15

Legal Events

Date	Code	Title
2003-01-12	FF	Patent granted
2003-03-12	KB	Patent renewed
2007-05-21	KB	Patent renewed
2011-02-28	KB	Patent renewed
2015-09-24	MM9K	Patent not in force due to non-payment of renewal fees

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CA2025005A1 (en)	1991-03-12	Condensed diazepinones, process for preparing them and pharmaceutical compositions containing these compounds
WO1994007891A1 (en)	1994-04-14	1-substituted oxindoles and azaoxindoles as novel cognition enhancers
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EP0813534A1 (en)	1997-12-29	6-ARYL PYRAZOLO 3,4-d]PYRIMIDIN-4-ONES AND COMPOSITIONS AND METHODS OF USE THEREOF
JP2004526769A (ja)	2004-09-02	子宮収縮抑制オキシトシン受容体拮抗薬としての新規三環系ピリジルベンズアゼピンカルボキサミドおよびその誘導体
US6323197B1 (en)	2001-11-27	Condensed 2,3-benzodiazepine derivatives and their use as AMPA-receptor inhibitors
WO1994006793A1 (en)	1994-03-31	3,3'-DISUBSTITUTED-1,3-DIHYDRO-2H-PYRROLO[2,3-b]HETEROCYCLIC-2-ONE USEFUL IN THE TREATMENT OF COGNITIVE DISORDERS OF MAN
JP2018521022A (ja)	2018-08-02	Ｔｎｆ活性のモジュレーターとしての縮合三環式イミダゾピラジン類
NZ255821A (en)	1996-10-28	3-oxo-pyrido-(or 4-oxo-azepino)[1,2-a]benzimidazole-4(or 5)-carboxyl derivatives; medicament
CZ251995A3 (en)	1996-01-17	Disubstituted polycyclic compounds and their derivatives per se and for therapy as well as pharmaceutical compositions based thereon
JP2003516994A (ja)	2003-05-20	認知能力を向上させるための置換１，２，３−トリアゾロ［１，５−ａ］キナゾリン
AU741162B2 (en)	2001-11-22	New 2,3-benzodiazepine derivatives
Barluenga et al.	1993	Intramolecular Friedel-Crafts cyclization of nitrogen heterocycles. An expeditious approach to the azaphenanthrene skeleton
AU2005238220A1 (en)	2005-11-10	Enantiomer-pure hexahydro- pyrrolocyclopenta- pyridine derivatives