DE2732921A1 - 1-Piperazino-triazolo-thieno-diazepine derivs. - useful as anxiolytics, tranquillisers, sedatives and neuroleptics - Google Patents
1-Piperazino-triazolo-thieno-diazepine derivs. - useful as anxiolytics, tranquillisers, sedatives and neurolepticsInfo
- Publication number
- DE2732921A1 DE2732921A1 DE19772732921 DE2732921A DE2732921A1 DE 2732921 A1 DE2732921 A1 DE 2732921A1 DE 19772732921 DE19772732921 DE 19772732921 DE 2732921 A DE2732921 A DE 2732921A DE 2732921 A1 DE2732921 A1 DE 2732921A1
- Authority
- DE
- Germany
- Prior art keywords
- general formula
- thieno
- diazepine
- compounds
- bromo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- -1 tranquillisers Substances 0.000 title claims description 29
- 239000002249 anxiolytic agent Substances 0.000 title description 2
- 230000000949 anxiolytic effect Effects 0.000 title description 2
- 229940005530 anxiolytics Drugs 0.000 title 1
- 229940125723 sedative agent Drugs 0.000 title 1
- 239000000932 sedative agent Substances 0.000 title 1
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 11
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 5
- 125000005843 halogen group Chemical group 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 24
- 150000004911 1,4-diazepines Chemical class 0.000 claims description 17
- POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 claims description 17
- 239000004480 active ingredient Substances 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 239000000460 chlorine Chemical group 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 239000000969 carrier Substances 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000005059 halophenyl group Chemical group 0.000 claims description 3
- 125000006501 nitrophenyl group Chemical group 0.000 claims description 3
- 150000004885 piperazines Chemical class 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 208000001431 Psychomotor Agitation Diseases 0.000 claims description 2
- 206010037211 Psychomotor hyperactivity Diseases 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 230000002920 convulsive effect Effects 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 4
- 239000013543 active substance Substances 0.000 claims 2
- 239000012876 carrier material Substances 0.000 claims 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002253 acid Substances 0.000 abstract description 3
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- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 abstract 1
- 230000034994 death Effects 0.000 abstract 1
- 231100000517 death Toxicity 0.000 abstract 1
- 125000004663 dialkyl amino group Chemical group 0.000 abstract 1
- 150000004908 diazepines Chemical class 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 125000000714 pyrimidinyl group Chemical group 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
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- 229920002472 Starch Polymers 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
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- ONOBXDPYDHTSBQ-UHFFFAOYSA-N 2,3,4,7-tetrahydro-1h-diazepine Chemical compound C1CC=CCNN1 ONOBXDPYDHTSBQ-UHFFFAOYSA-N 0.000 description 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 2
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- 108010010803 Gelatin Proteins 0.000 description 2
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- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 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 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
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- QAQNWCMGKXMUQT-UHFFFAOYSA-N 6,7-dihydro-1h-1,4-diazepine Chemical class C1CC=NC=CN1 QAQNWCMGKXMUQT-UHFFFAOYSA-N 0.000 description 1
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- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D495/12—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 three hetero rings
- C07D495/14—Ortho-condensed systems
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- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Description
Neue substituierte l-Acyl-piperidino- bzw.-piperazino-4H-s-New substituted l-acyl-piperidino- or -piperazino-4H-s-
triazolo[3,4cithieno[2,3e]l,4-diazepine, Verfahren zu ihrer Herstellung und pharmazeutische Zusammensetzungen Die Erfindung betrifft neue substituierte l-Acyl-piperidino-bzw.-piperazino-4H-s-triazolo [3,4c] thieno [2,3e] 1,4 diazepine der allgemeinen Formel in der R1 Wasserstoff, Alkyl mit 1 - 17 Kohlenstoffatomen, Alkoxy mit 1 - 2 Kohlenstoffatomen, Phenyl, Tolyl, Methoxyphenyl, Halogenphenyl, Nitrophenyl oder Pyridyl, R2 Fluor, Chlor oder Brom, R3 Brom, Chlor oder Alkyl mit 1 - 3 Kohlenstoffatomen und Y N oder die Gruppe CH bedeuten, Verfahren zu ihrer Herstellung und ihre Verwendung als Wirkstoffe in Arzneimitteln.triazolo [3,4cithieno [2,3e] 1,4-diazepines, process for their preparation and pharmaceutical compositions The invention relates to new substituted l-acyl-piperidino- or -piperazino-4H-s-triazolo [3,4c] thieno [2,3e] 1,4 diazepines of the general formula in which R1 is hydrogen, alkyl with 1 - 17 carbon atoms, alkoxy with 1 - 2 carbon atoms, phenyl, tolyl, methoxyphenyl, halophenyl, nitrophenyl or pyridyl, R2 is fluorine, chlorine or bromine, R3 is bromine, chlorine or alkyl with 1 - 3 carbon atoms and YN or the group CH mean processes for their production and their use as active ingredients in pharmaceuticals.
In der allgemeinen Formel I bedeutet der Ausdruck "Alkyl" einen geradkettigen oder verzweigten Alkylrest mit 1 - 17 Kohlensto;fatomen; bevorzugt sind 1 - 6 Kohlenstoffatome.In the general formula I, the term "alkyl" means a straight chain or branched alkyl radical with 1 - 17 carbon atoms; 1 to 6 carbon atoms are preferred.
"Halogen" bezeichnet die Halogenatome Fluor, Chlor, Brom und Jod; der Substituent am Phenylring kann in o-, m- oder p-Stellung stehen. Der Pyridylrest kann in a-, B- oder br-Stellung zum Stickstoffatom mit dem Piperidin- bzw."Halogen" refers to the halogen atoms fluorine, chlorine, bromine and iodine; the substituent on the phenyl ring can be in the o-, m- or p-position. The pyridyl residue can be in a-, B- or br-position to the nitrogen atom with the piperidine resp.
Piperazinring verbunden sein.Be connected to piperazine ring.
Man kann die neuen Verbindungen erhalten a) durch Acylierung einer Verbindung der allgemeinen Formel in der die Reste R2, R3 und Y die oben angegebene Bedeutung haben, oder b) durch Cyclisierung von Verbindungen der allgemeinen Formel in der die Reste R1, R2 und R3 die oben angegebene Bedeutung haben und Y für CH steht, oder c) durch Dehydrierung von Verbindungen der allgemeinen Formel in der R1, R2, R3 und Y die oben angegebene Bedeutung haben, oder d) durch Umsetzung von Verbindungen der allgemeinen Formel in der R2 und R3 die oben angegebene Bedeutung haben, mit Piperazinen der allgemeinen Formel in der R1 die oben angegebene Bedeutung hat.The new compounds can be obtained a) by acylating a compound of the general formula in which the radicals R2, R3 and Y have the meaning given above, or b) by cyclization of compounds of the general formula in which the radicals R1, R2 and R3 have the meaning given above and Y stands for CH, or c) by dehydrogenation of compounds of the general formula in which R1, R2, R3 and Y have the meaning given above, or d) by reacting compounds of the general formula in which R2 and R3 have the meaning given above, with piperazines of the general formula in which R1 has the meaning given above.
Die Acylierung von Verbindungen der Formel II mit einem Piperidin- bzw. Piperazincarbonsäurehalogenid bzw. -anhydrid kann unter Verwendunge eines Uberschusses an Acylierungsmittel oder aber in einem geeigneten inerten Lösungsmittel wie Dioxan, Tetrahydrofuran, Benzol, Toluol oder Xylol erfolgen. In manchen Fällen hat sich der Zusatz einer anorganischen oder organischen Base, beispielsweise von Pyridin, Triäthylamin, Pottasche oder Kaliumbicarbonat zum Abfangen der Säure als nützlich erwiesen. Reaktionstemperatur und Reaktionszeit können, je nach dem eingesetzten Ausgangsmaterial, in weiten Grenzen variieren. So kann die Raktionstemperatur zwischen Raumtemperatur und dem Siedepunkt des verwendeten Lösungsmittels bzw. des Acylierungsmittels liegen; die Reaktionszeit kann wenige Minuten bis mehrere Stunden betragen.The acylation of compounds of the formula II with a piperidine or piperazine carboxylic acid halide or anhydride can using an excess on acylating agents or in a suitable inert solvent such as dioxane, Tetrahydrofuran, benzene, toluene or xylene take place. In some cases it has the addition of an inorganic or organic base, for example pyridine, Triethylamine, potash, or potassium bicarbonate are useful for scavenging the acid proven. Reaction temperature and reaction time can, depending on the one used Starting material, vary within wide limits. So the reaction temperature can be between Room temperature and the boiling point of the solvent or acylating agent used lie; the reaction time can be a few minutes to several hours.
Der Ringschluß von Verbindungen der allgemeinen Formel III gelingt bevorzugt durch Kochen mit einem höher siedenden Lösungsmittel wie Dioxan, Tetrahydrofuran, Benzol, Toluol oder Xylol unter Rückfluß. Bei den meisten Verbindungen erfolgt hierbei ein spontaner Ringschluß; falls der Ringschluß auf diese Weise nicht oder nicht vollständig erreicht werden kann, genügt die Zugabe von Kieselgel und Erhitzen am Wasserabscheider. Die Reaktionszeit reicht auch bei diesem Verfahren von wenigen Minuten bis zu mehreren Stunden, je nach dem eingesetzten Ausgangsmaterial.The ring closure of compounds of the general formula III succeeds preferably by boiling with a higher boiling solvent such as dioxane, tetrahydrofuran, Benzene, toluene or xylene under reflux. Most connections use this a spontaneous ring closure; if the ring closure is not or not in this way can be fully achieved, the addition of silica gel and heating on is sufficient Water separator. The reaction time in this process is also of a few Minutes to several hours, depending on the raw material used.
Die Dehydrierung von Verbindungen der allgemeinen Formel IV erfolgt unter Verwendung geeigneter Dehydrierungsmittel wie z.B. von Halogenen oder auch von Verbindungen der höheren Oxydationsstufen des Chroms oder Mangans, beispielsweise eines Chromats, eines Bichromats oder eines Permanganats.The dehydrogenation of compounds of the general formula IV takes place using suitable dehydrating agents such as halogens or else of compounds of the higher oxidation states of chromium or manganese, for example a chromate, a bichromate or a permanganate.
Als geeignete Lösungsmittel für die Umsetzung mit einem Halogen seien Chlorkohlenwasserstoffe wie Chloroform oder Methylenchlorid genannt. Die Oxydation mit den erwähnten Verbindungen des Chroms oder Mangans erfolgt in Lösungsmitteln wie Aceton, Tetrahydrofuran oder Dioxan.Suitable solvents for the reaction with a halogen are Called chlorinated hydrocarbons such as chloroform or methylene chloride. The oxidation with the mentioned compounds of chromium or manganese takes place in solvents such as acetone, tetrahydrofuran or dioxane.
Je nach Art des Oxydationsmittels liegt die Reaktionstemperatur im allgemeinen zwischen OOC und der Siedetemperatur des verwendeten Lösungsmittels.Depending on the type of oxidizing agent, the reaction temperature is im generally between OOC and the boiling point of the solvent used.
Die Umsetzung von Verbindungen der allgemeinen Formel V mit einem Piperazin der Formel VI erfolgt entweder ohne Lösungsmittel oder in höher siedenden Lösungsmitteln wie Benzol, Toluol, Dioxan, Tetrahydrofuran, Chlorkohlenwasserstoffen wie Tetrachlorkohlenstoff oder Methylenchlorid, vorzugsweise bei der Siedetemperatur des jeweils verwendeten Lösungsmittels. Die Reaktionsdauer ist abhängig vom eingesetzten Ausgangsmaterial und kann wenige Minuten bis mehrere Stunden betragen.The implementation of compounds of the general formula V with a Piperazine of the formula VI takes place either without a solvent or in a higher-boiling one Solvents such as benzene, toluene, dioxane, tetrahydrofuran, chlorinated hydrocarbons such as carbon tetrachloride or methylene chloride, preferably at the boiling point of the solvent used in each case. The reaction time depends on the one used Starting material and can take a few minutes to several hours.
Nach den vorstehend angegebenen Verfahren können beispielsweise die folgenden Endprodukte erhalten werden: 8-Brom-6- (o-chlorphenyl )-l-N-formylpiperazino-4H-s-triazolo [3,4c]thieno[2,3e]l,4-diazepin, l-(N-Acetylpiperazino)-8-brom-6-(o-chlorphenyl)-4H-striazolo[3,4c]thieno[2,3e]1,4-diazepin, l-(N-Acetylpiperazino)-8-äthyl-6-(o-chlorphenyl)-4H-striazolo[3,4c]thieno[2,3e]1,4-diazepin, l-(N-Acetylpiperazino)-8-chlor-6- (o-chlorphenyl)-4H-striazolo[3,4c]thieno[2,3e]1,4-diazepin, l-(N-Acetylpiperazino)-8-brom-6-(o-fluorphenyl)-4H-striazolo(3,4cithieno[2,3e]l,4-diazepin, l-(N-Acetylpiperazino)-8-brom-6-(o-bromphenyl)-4H-striazolo[3,4c]thienot2,3e]1,4-diazepin, 8-Brom-6-(o-chlorphenyl)-1-(N-stearylpiperazino)-4H-striazolo3,4c]thienoC2,3e11,4-diazepin, 8-Brom-l-(N-caproylpiperazino)-6-(o-chlorphenyl)-4H-striazolo[3,4c]thieno[2,3e]1,4-diazepin, 8-Brom-6-(o-chlorphenyl)-1-(N-benzoylpiperazino)-4H-striazoloC3,4c)thienoC2,3e]1,4-diazepin, 8-Brom-6-(o-chlorphenyl)-1-[N-(p-fluorbenzoyl)-piperazino]-4H-s-triazolo[3,4c]thieno[2,3e]1,4-diazepin, 8-Brom-6-(o-chlorphenyl)-1-[N-(o-methylbenzoyl)-piperazino]-4H-s-triazolo[3,4c]thieno[2,3e]1,4-diazepin, 8-Brom-6-(o-chlorphenyl)-1-[N-(p-chlorbenzoyl)-piperazino]-4H-s-triazolo[3,4c]thieno[2,3e]1,4-diazepin, 8-Brom-6-(o-chlorphenyl)-1-tN-(p-nitrobenzoyl)-piperazino]-4H-s-triazolo[3,4c]thieno[2,3e]1,4-diazepin, 8-Brom-6-(o-chlorphenyl)-1-(N-nicotinoyl-piperazino)-4H-striazolot3,4c]thienot2,3e]1,4-diazepin, 8-Brom-6-(o-chlorphenyl)-1-(N-picolinoyl-piperazino)-4H-striazoloC3,4c]thieno[2,3e1,4-diazepin, l-(N-Äthoxycarbonyl-piperazino)-8-brom-6- (o-chlorphenyl) 4H-s-triazolo[3,4c]thieno[2,3e]1,4-diazepin, 8-Brom-6- (o-bromphenyl)-l-(N-formylpiperidino)-4H-striazolo[3,4c]thieno[2,3e]1,4-diazepin, l-(N-Acetylpiperidino)-8-brom-6-(o-chlorphenyl)-4H-striazolo[3,4c]thieno[2,3e]l,4-diazepin, 8-Brom-6- (o-chlorphenyl)-l-(N-benzoylpiperidino)-4H-s triazolo[3,4c]thieno[2,3e]l,4-diazepin, 8-Brom-6-(o-chlorphenyl)-1-[N-(p-fluorbenzoyl)-piperidino]-4H-s-triazolo[3,4c]thieno[2,3e]1,4-diazepin, 8-Brom-l-(N-isobutyrylpiperidino)-6-(o-chlorphenyl)-4H-striazolo[3,4c]thieno[2,3e]l,4-diazepin.According to the method given above, for example, the the following end products are obtained: 8-Bromo-6- (o-chlorophenyl) -l-N-formylpiperazino-4H-s-triazolo [3,4c] thieno [2,3e] 1,4-diazepine, 1- (N-acetylpiperazino) -8-bromo-6- (o -chlorophenyl) -4H-striazolo [3,4c] thieno [2,3e ] 1,4-diazepine, l- (N-Acetylpiperazino) -8-ethyl-6- (o-chlorophenyl) -4H-striazolo [3,4c] thieno [2,3e] 1,4-diazepine, l- (N-acetylpiperazino) -8-chloro-6- (o-chlorophenyl) -4H-striazolo [3,4c] thieno [2,3e] 1,4-diazepine, 1- (N-acetylpiperazino) -8-bromo-6- (o-fluorophenyl) -4H-striazolo ( 3,4cithieno [2,3e] 1,4-diazepine, l- (N-acetylpiperazino) -8-bromo-6- (o-bromophenyl) -4H-striazolo [3,4c] thienot2,3e] 1,4-diazepine, 8-bromo-6- (o-chlorophenyl) -1- (N-stearylpiperazino) -4H-striazolo3,4c] thienoC2,3e11,4-diazepine, 8-bromo-1- (N-caproylpiperazino) -6- (o-chlorophenyl) -4H-striazolo [3,4c] thieno [2,3e] 1,4-diazepine, 8-bromo-6- (o-chlorophenyl) -1- (N-benzoylpiperazino) -4H-striazoloC3,4c) thienoC2,3e] 1,4-diazepine, 8-bromo-6- (o-chlorophenyl) -1- [N- (p-fluorobenzoyl) -piperazino] -4H-s-triazolo [3,4c] thieno [2,3e] 1,4-diazepine, 8-Bromo-6- (o-chlorophenyl) -1- [N- (o-methylbenzoyl) -piperazino] -4H-s-triazolo [3,4c] thieno [2,3e] 1,4-diazepine, 8-bromo-6- (o-chlorophenyl) -1- [N- (p-chlorobenzoyl) piperazino] -4H-s-triazolo [3,4c] thieno [2,3e] 1,4-diazepine, 8-Bromo-6- (o-chlorophenyl) -1-tN- (p-nitrobenzoyl) -piperazino] -4H-s-triazolo [3,4c] thieno [2,3e] 1,4-diazepine, 8-bromo-6- (o-chlorophenyl) -1- (N-nicotinoyl-piperazino) -4H-striazolot3,4c] thienot2,3e] 1,4-diazepine, 8-bromo-6- (o-chlorophenyl) -1- (N-picolinoyl-piperazino) -4H-striazoloC3,4c] thieno [2,3e1,4-diazepine, l- (N-ethoxycarbonyl-piperazino) -8-bromo-6- (o-Chlorophenyl) 4H-s-triazolo [3,4c] thieno [2,3e] 1,4-diazepine, 8-bromo-6- (o -bromophenyl) -1- (N-formylpiperidino) -4H-striazolo [3,4c] thieno [2,3e] 1,4-diazepine, l- (N-Acetylpiperidino) -8-bromo-6- (o-chlorophenyl) -4H-striazolo [3,4c] thieno [2,3e] 1,4-diazepine, 8-Bromo-6- (o-chlorophenyl) -l- (N-benzoylpiperidino) -4H-s triazolo [3,4c] thieno [2,3e] 1,4-diazepine, 8-bromo-6- (o-chlorophenyl) -1- [N- (p-fluorobenzoyl) -piperidino] -4H-s-triazolo [3,4c] thieno [2,3e] 1,4-diazepine, 8-Bromo-1- (N-isobutyrylpiperidino) -6- (o -chlorophenyl) -4H-striazolo [3,4c] thieno [2,3e] 1,4-diazepine.
Die Ausgangsverbindungen der allgemeinen Formel II können z.B. erhalten werden gemäß den Angaben im DBP (deutsche Patentanmeldung P , Case 1/586) durch Umsetzung entsprechend substituierter l-Halogen-4H-s-triazolo[ 3, 4c] thieno[2,3e]l,4-diazepine mit einem Piperazin oder durch Dehydrierung eines l-Piperazinyl-4H-s-triazolo[3,4c]thieno t2,3e]5,6-dihydro-1,4-diazepins.The starting compounds of the general formula II can be obtained, for example are carried out according to the information in the DBP (German patent application P, Case 1/586) Implementation of appropriately substituted l-halo-4H-s-triazolo [3, 4c] thieno [2,3e] 1,4-diazepines with a piperazine or by dehydration of a l-piperazinyl-4H-s-triazolo [3,4c] thieno t2.3e] 5,6-dihydro-1,4-diazepines.
Ausgangsstoffe der allgemeinen Formel III lassen sich herstellen durch Umsetzung von Thieno-benzodiazepin-2-thionen der allgemeinen Formel in der R2 und R3 die oben angeführte Bedeutung haben, mit einem N-Acylpiperidincarbonsäurehydrazid der allgemeinen Formel in der R1 die oben angegebene Bedeutung hat.Starting materials of the general formula III can be prepared by reacting thieno-benzodiazepine-2-thiones of the general formula in which R2 and R3 have the meaning given above, with an N-acylpiperidinecarboxylic acid hydrazide of the general formula in which R1 has the meaning given above.
Verbindungen der allgemeinen Formel IV erhält man durch Umsetzung von Verbindungen der allgemeinen Formel in der R2 und R3 die oben genannte Bedeutung haben, mit einem Piperazinderivat der allgemeinen Formel in der R1 die oben genannte Bedeutung hat und anschließendem Austausch des Ringsauerstoffatoms durch ein Stickstoffatom, wie z.B. in der deutschen Anmeldung P 25 31 678 beschrieben worden ist.Compounds of the general formula IV are obtained by reacting compounds of the general formula in which R2 and R3 have the abovementioned meaning, with a piperazine derivative of the general formula in which R1 has the meaning given above and the subsequent replacement of the ring oxygen atom by a nitrogen atom, as has been described, for example, in German application P 25 31 678.
Die Endprodukte der allgemeinen Formel I weisen wertvolle therapeutische Eigenschaften auf. Bei der Anwendung verschiedener pharmakologischer Testmethoden zeigen sie zunächst eine signifikante neuroleptische Wirkung; mit deren Abklingen entwickelt sich nach etwa 24 bis 48 Stunden eine anxiolytische, spannungslösende und sedierende Wirkung.The end products of general formula I have valuable therapeutic properties Properties on. When using various pharmacological test methods do they initially show a significant neuroleptic effect; with their fading away After about 24 to 48 hours, an anxiolytic, tension-relieving effect develops and sedative effect.
Die neuen Verbindungen sind daher besonders geeignet zur Behebung psychomotorischer Erregungs- und Angstzustände, wie sie beispielsweise bei Schizophrenie auftreten, ferner zur Behandlung von Krampfzuständen und Schlafstörungen verschiedener Genese.The new connections are therefore particularly suitable for rectification psychomotor agitation and anxiety, such as those in schizophrenia occur, also for the treatment of convulsive states and sleep disorders of various Genesis.
Als besonders wirksam haben sich solche Endprodukte der allgemeinen Formel I erwiesen, in denen R1 Wasserstoff oder Methyl, R2 Chlor, R3 Brom und Y Ch oder N bedeuten.Such end products have proven to be particularly effective in general Formula I proved, in which R1 is hydrogen or methyl, R2 is chlorine, R3 is bromine and Y Ch or N mean.
Die Einzeldosis der erfindungsgemäßen Substanzen liegt bei 0,05 bis 50, vorzugsweise 0,1 bis 25 mg und bei 5 bis 150 mg als Tagesdosis.The single dose of the substances according to the invention is from 0.05 to 50, preferably 0.1 to 25 mg and 5 to 150 mg as the daily dose.
Die erfindungsgemäß erhältlichen Verbindungen können allein oder in Kombination mit anderen erfindungsgemäßen Wirkstoffen, gegebenenfalls auch in Kombination mit weiteren pharmakologisch aktiven Wirkstoffen wie Spasmolytika oder B-Rezeptorenblocker zur Anwendung gelangen. Geeignete Anwendungsformen sind beispielsweise Tabletten, Kapseln, Zäpfchen, Lösungen, Säfte, Emulsionen oder dispersible Pulver. Entsprechende Tabletten können beispielsweise durch Mischen des oder der Wirkstoffe mit bekannten Hilfsstoffen, beispielsweise inerten Verdünnungsmitteln, wie Calciumcarbonat, Calciumphosphat oder Milchzucker, Sprengmitteln, wie Maisstärke oder Alginsäure, Bindemitteln, wie Stärke oder Gelatine, Schmiermitteln, wie Magnesiumstearat oder Talk, und/oder Mitteln zur Erzielung des Depoteffektes, wie Carboxypolymethylen, Carboxymethylcellulose, celluloseacetatphthalat, oder Polyvinylacetat erhalten werden. Die Tabletten können auch aus mehreren Schichten bestehen.The compounds obtainable according to the invention can be used alone or in Combination with other active ingredients according to the invention, optionally also in combination with other pharmacologically active ingredients such as antispasmodics or B-receptor blockers come into use. Suitable application forms are, for example, tablets, Capsules, suppositories, solutions, juices, emulsions or dispersible powders. Appropriate Tablets can be made, for example, by mixing the active ingredient (s) with known ones Auxiliaries, for example inert diluents such as calcium carbonate, calcium phosphate or lactose, disintegrants such as corn starch or alginic acid, binders such as Starch or gelatin, lubricants such as magnesium stearate or talc, and / or agents to achieve the depot effect, such as carboxypolymethylene, carboxymethyl cellulose, cellulose acetate phthalate, or polyvinyl acetate. The tablets can also consist of several layers.
Entsprechend können Dragees durch Überziehen von analog den Tabletten hergestellten Kerner mit üblicherweise in Drageeüberzügen verwendeten Mitteln, beispielsweise Kollidon oder Schellack, Gummi arabicum, Talk, Titandioxid oder Zucker, hergestellt werden. Zur Erzielung eines Depoteffektes oder zur Vermeidung von Inkompatibilitäten kann der Kern auch aus mehreren Schichten bestehen. Desgleichen kann auch die Drageehülle zur Erzielung eines Depoteffektes aus mehreren Schichten bestehen, wobei die oben bei den Tabletten erwähnten Hilfsstoffe verwendet werden können.Correspondingly, coated tablets can be made by coating analogously to the tablets manufactured Kerner with agents commonly used in dragee coatings, for example Kollidon or shellac, gum arabic, talc, titanium dioxide or sugar will. To achieve a depot effect or to avoid incompatibilities the core can too consist of several layers. Likewise The coated tablet can also consist of several layers to achieve a depot effect exist, the excipients mentioned above for the tablets being used can.
Säfte der erfindungsgemäßen Wirkstoffe bzw. Wirkstoffkombinationen können zusätzlich noch ein Süßungsmittel, wie Saccharin, Cyclamat, Glycerin oder Zucker sowie ein geschmacksverbesserndes Mittel, z.B. Aromastoffe, wie Vanillin oder Orangenextrakt, enthalten. Sie können außerdem Suspendierhilfsstoffe oder Dickungsmittel, wie Natriumcarboxymethylcellulose, Netzmittel, beispielsweise Kondensationsprodukte von Fettalkoholen mit Äthylenoxid, oder Schutzstoffe, wie p-Hydroxybenzoate, enthalten.Juices of the active ingredients or combinations of active ingredients according to the invention can also use a sweetener such as saccharin, cyclamate, glycerin or Sugar and a flavor-enhancing agent, e.g. flavorings such as vanillin or orange extract. You can also use suspension aids or thickeners, such as sodium carboxymethyl cellulose, wetting agents, for example condensation products of fatty alcohols with ethylene oxide, or protective substances such as p-hydroxybenzoates.
Die eine oder mehrere Wirkstoffe bzw. Wirkstoffkombinationen enthaltenden Kapseln können beispielsweise hergestellt werden, indem man die Wirkstoffe mit inerten Trägern, wie Milchzucker oder Sorbit, mischt und in Gelatinekapseln einkapselt.The one or more active ingredients or combinations of active ingredients Capsules can be produced, for example, by combining the active ingredients with inert Carriers, such as lactose or sorbitol, mixed and encapsulated in gelatin capsules.
Geeignete Zäpfchen lassen sich beispielsweise durch Vermischen mit dafür vorgesehenen Trägermitteln, wie Neutralfetten oder Polyäthylenglykol bzw. dessen Derivaten, herstellen.Suitable suppositories can be made, for example, by mixing with Carriers provided for this purpose, such as neutral fats or polyethylene glycol or its derivatives.
Beispiel 1 l-(N-Acetvlpiperazino)-8-brom-6-(o-chlorshenyl)-4H-striazolo[3,4c]thieno[2,3e]1,4-diazepin 4,6 g (0,01 Mol) 8-Brom-6-(o-chlorphenyl)l-piperazino-4H-striazolo[3,4c]thieno[2,3e]l,4-diazepin werden in 100 ml Essigsäureanhydrid 20 Minuten gerührt. Man gießt das Reaktionsgemisch auf Eis und macht mit Ammoniak alkalisch.Example 1 1- (N-acetylpiperazino) -8-bromo-6- (o -chloroshenyl) -4H-striazolo [3,4c] thieno [2,3e] 1,4-diazepine 4.6 g (0.01 mol) of 8-bromo-6- (o-chlorophenyl) l-piperazino-4H-striazolo [3,4c] thieno [2,3e] 1,4-diazepine are stirred in 100 ml of acetic anhydride for 20 minutes. The reaction mixture is poured on ice and makes alkaline with ammonia.
Die Acetylverbindung wird in Methylenchlorid aufgenommen, die Methylenchloridphase getrocknet und der Rückstand durch Ätherzugabe zur Kristallisation gebracht.The acetyl compound is taken up in methylene chloride, the methylene chloride phase dried and the residue brought to crystallization by adding ether.
Ausbeute: 3,8 g = 76 % d.Th. vom Fp. 247 - 2490C.Yield: 3.8 g = 76% of theory of m.p. 247-2490C.
BeisDiel 2 l-(N-AcetYl-4-piperidino)-8-brom-6-(o-chlorPhenyl)-4H-striazolor3.4clthienor2.3e]1.4-diazepin 7,43 g (0,02 Mol) 7-Brom-5-(o-chlorphenyl)-1,4-diazepin-2-thion werden mit 4 g N-Acetyl-4-piperidincarbonsäurehydrazid und 150 ml Dioxan 4 Stunden unter Rückfluß gekocht. Man dampft das Reaktionsgemisch ein und erhält nach Ätherzugabe 2,7 g eines halbkristallinen Produktes, das man in 60 ml Xylol und 14 g Kieselgel 2 Stunden am Wasserabscheider erhitzt. Die Suspension wird abgesaugt und die Titelverbindung mit Methanol eluiert. Man erhält nach entsprechender Reinigung 2,4 g = 25 % d.Th. der Titelverbindung vom Fp. 221 - 2230C.For example 2 l- (N-AcetYl-4-piperidino) -8-bromo-6- (o-chlorophenyl) -4H-striazolor3.4clthienor2.3e] 1,4-diazepine 7.43 g (0.02 mol) of 7-bromo-5- (o-chlorophenyl) -1,4-diazepine-2-thione are mixed with 4 g of N-acetyl-4-piperidinecarboxylic acid hydrazide and 150 ml of dioxane refluxed for 4 hours. The reaction mixture is evaporated and after the addition of ether, 2.7 g of a semi-crystalline product are obtained heated in 60 ml of xylene and 14 g of silica gel for 2 hours on a water separator. The suspension is filtered off with suction and the title compound is eluted with methanol. One obtains according to the corresponding Purification 2.4 g = 25% of theory the title compound of m.p. 221-2230C.
Beispiel 3 8-Brom-6-(o-chlorphenvl)-1-(N-äthoxYcarbonYlPiperazino)-4H-s-triazolo[3,4c]thieno[2,3e]1,4-diazepin, 4,6 g (0,01 Mol) 8-Brom-6-(o-chlorphenyl)-l-piperazino-4H-s-triazolo[3,4c]thieno[2,3e]1,4-diazepin werden in 100 ml Tetrahydrofuran mit 2 ml Chlorameisensäureäthylester 30 Minuten bei Raumtemperatur gerührt. Man dampft ein, gießt Wasser und Methylenchlorid hinzu, macht mit Ammoniak alkalisch und chromatographiert den Rückstand aus der getrockneten Methylenchloridphase.Example 3 8-Bromo-6- (o-chlorophenyl) -1- (N-ethoxy carbonyl piperazino) -4H-s-triazolo [3,4c] thieno [2,3e] 1,4-diazepine, 4.6 g (0.01 mole) of 8-bromo-6- (o -chlorophenyl) -l-piperazino-4H-s-triazolo [3,4c] thieno [2,3e] 1,4-diazepine are in 100 ml of tetrahydrofuran with 2 ml of ethyl chloroformate for 30 minutes stirred at room temperature. It is evaporated, water and methylene chloride are poured in, make alkaline with ammonia and chromatograph the residue from the dried Methylene chloride phase.
Ausbeute: 4,8 g = 91 % d.Th., Fp. 216 - 2180C.Yield: 4.8 g = 91% of theory, melting point 216-2180C.
Beispiel 4 1-(N-Formylpiperazino)-8-brom-6-(o-chlorphehyl)-4H-striazolo[3,4c]thieno[2,3e]1,4-diazepin 4,6 g (0,01 Mol) 8-Brom-6-(o-chlorphenyl)-l-piperazino-4H-s-triazolo[3,4c]thieno[2,3e]1,4-diazepin werden in 100 ml Ameisensäure 3 Stunden unter Rückfluß gekocht.Example 4 1- (N-Formylpiperazino) -8-bromo-6- (o-Chlorophyl) -4H-striazolo [3,4c] thieno [2,3e] 1,4-diazepine 4.6 g (0.01 mole) of 8-bromo-6- (o -chlorophenyl) -l-piperazino-4H-s-triazolo [3,4c] thieno [2,3e] 1,4-diazepine are refluxed in 100 ml of formic acid for 3 hours.
Man gießt auf Eis, macht mit 2 n Natronlauge alkalisch, nimmt die Formylverbindung in Methylenchlorid auf und arbeitet wie unter Beispiel 1 auf.It is poured onto ice, made alkaline with 2N sodium hydroxide solution and taken Formyl compound in methylene chloride and works up as in Example 1.
Ausbeute: 3,9 g 5 80 % d.Th., Fp. 205 - 215°C.Yield: 3.9 g of 80% of theory, melting point 205-215 ° C.
Auf analoge Weise erhält man weitere Verbindungen der allgemeinen
Formel I wie die nachstehende Tabelle zeigt:
Dragee-Endgewicht: 100 mg b) Tabletten Wirkstoff gemäß der Erfindung 0,5 mg Milchzucker 50,0 mg Maisstärke 43,5 mg lösliche Stärke 5,0 mg Magnesiumstearat 1,0 mg 100,0 mg Herstellung: Wirkstoff und Magnesiumstearat werden mit einer wässrigen Lösung der löslichen Stärke granuliert, das Granulat getrocknet und innig mit Milchzucker und Maisstärke vermischt. Das Gemisch wird sodann zu Tabletten von 100 mg Gewicht verpreßt, die Je 0,5 mg Wirkstoff enthalten. Dragee final weight: 100 mg b) tablets active ingredient according to the invention 0.5 mg lactose 50.0 mg corn starch 43.5 mg soluble starch 5.0 mg magnesium stearate 1.0 mg 100.0 mg Production: Active ingredient and magnesium stearate are made granulated with an aqueous solution of the soluble starch, the granules dried and intimately mixed with milk sugar and corn starch. The mixture then becomes tablets of 100 mg weight, each containing 0.5 mg of active ingredient.
c) Suppositorien 1 Zäpfchen enthält: Wirkstoff gemäß der Erfindung 5,0 mg Zäpfchenmasse 1.695,0 mg Herstellung: Die feingepulverte Substanz wird mit Hilfe eines Eintauch-Homogenisators in die geschmolzene auf 400C abgekühlte Zäpfchenmasse eingerührt. Die Masse wird bei 35 0C in leicht vorgekühlte Formen gegossen.c) Suppositories 1 suppository contains: active ingredient according to the invention 5.0 mg suppository mass 1,695.0 mg Production: The finely powdered substance is mixed with Using an immersion homogenizer in the melted suppository mass cooled to 400C stirred in. The mass is poured into slightly pre-cooled molds at 35 ° C.
Claims (13)
Priority Applications (38)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772732921 DE2732921A1 (en) | 1977-07-21 | 1977-07-21 | 1-Piperazino-triazolo-thieno-diazepine derivs. - useful as anxiolytics, tranquillisers, sedatives and neuroleptics |
| FI782025A FI63033C (en) | 1977-07-21 | 1978-06-26 | FREQUENCY REQUIREMENT FOR ANXIOLYTIC TRANSQUILLATION OF SEED / ELLER NEUROLEPTIC SUBSTITUTES 1-PIPERAZINYL-4H-S-TRIAZOLO (3,4-C) THIENO (2,3-E) -1,4-DIAZEPERE |
| EP78100263A EP0000479B1 (en) | 1977-07-21 | 1978-06-28 | Substituted 1-piperazinyl-4h-s-triazolo (3,4-c)thieno(2,3-e)1,4-diazepines, process for their preparation and medicaments containing them |
| DE7878100263T DE2860404D1 (en) | 1977-07-21 | 1978-06-28 | Substituted 1-piperazinyl-4h-s-triazolo (3,4-c)thieno(2,3-e)1,4-diazepines, process for their preparation and medicaments containing them |
| GR56728A GR65022B (en) | 1977-07-21 | 1978-07-07 | Method for the preparation of new substituted i-piperazinylo-triazolo-thieno-1,4-diazepines |
| AT0498978A AT363949B (en) | 1977-07-21 | 1978-07-11 | METHOD FOR PRODUCING NEW SUBSTITUTED 1-PIPERAZINYL-TRIAZOLOTHIENO-1,4-DIAZEPINE AND ITS SALTS |
| US05/924,149 US4180573A (en) | 1977-07-21 | 1978-07-13 | 1-Piperazino-6-phenyl-4H-s-triazolo[3,4-c]thieno[2,3-e]1,4-diazepines |
| PH21384A PH14236A (en) | 1977-07-21 | 1978-07-17 | 1-piperazino-6-phenyl-4h-s-triazolo(3,4-c)thieno(2,3-e)1,4-diazepines,composition and method of use thereof |
| CH772878A CH642374A5 (en) | 1977-07-21 | 1978-07-18 | SUBSTITUTED 1-PIPERAZINYL-TRIAZOLO-THIENO-1,4-DIAZEPINE. |
| RO7894710A RO75609A (en) | 1977-07-21 | 1978-07-18 | PROCESS FOR THE PREPARATION OF SUBSTITUTED 1-PIPERAZINYL-TRIAZOLO-THINO-1,4-DIAZEPES |
| CS784821A CS209897B2 (en) | 1977-07-21 | 1978-07-19 | Method of making the new substituted 2-piperazinyl-4h-s-triazolo /3,4c/ thieno /2,3c/-1,4-diazepines |
| IL55169A IL55169A (en) | 1977-07-21 | 1978-07-19 | 1-piperazino-8-substituted-4h-s-triazolo(3,4-c)thieno(2,3-e)-1,4-diazepine derivatives,their preparation and pharmaceutical compositions containing them |
| BE189395A BE869136A (en) | 1977-07-21 | 1978-07-19 | NEWS 1-PIPERAZINYL-TRIAZOLO-THIENO-1,4-DIAZEPINES SUBSTITUTES |
| SU782638749A SU725564A3 (en) | 1977-07-21 | 1978-07-19 | Method of preparing substituted 1-piperazinyl-4h-s-triazolo/3,4-c/thieno/2,3-e/ 1,4-diazepines or their salts |
| IT50381/78A IT1107490B (en) | 1977-07-21 | 1978-07-19 | COMPOSITIONS OF 1-PIPERAZINYL-TRIAZOLE-TIENO-1/4-DIAZEPINES REPLACED AND PROCEDURE FOR THEIR PREPARATION |
| LU80002A LU80002A1 (en) | 1977-07-21 | 1978-07-19 | PROCESS FOR THE PREPARATION OF NEW SUBSTITUTED 1-PIPERAZINYL-TRIAZOLO-THIENO-1,4-DIAZEPINE |
| NL7807762A NL7807762A (en) | 1977-07-21 | 1978-07-20 | NEW SUBSTITUTED 1-PIPERAZINYL-TRIAZOLO-THIE-NO-1,4-DIAZEPINES. |
| ES471886A ES471886A1 (en) | 1977-07-21 | 1978-07-20 | Substituted 1-piperazinyl-4H-s-triazolo (3,4-c)thieno(2,3-e)1,4-diazepines, process for their preparation and medicaments containing them. |
| JP8889078A JPS5422395A (en) | 1977-07-21 | 1978-07-20 | Novel diazepine compound |
| NO782499A NO149889C (en) | 1977-07-21 | 1978-07-20 | ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE SUBSTITUTED 1-PIPERAZINYL-4H-S-TRIAZOLO (3.4C) TIENO (2,3E) -1,4-DIAZEPINES |
| PL1978208542A PL115061B1 (en) | 1977-07-21 | 1978-07-20 | Process for preparing novel substituted 1-piperazinylo-4h-sym-triazolo/3,4-c/thieno/2,3-e/-1,4-diazepins |
| GB7830584A GB2001972B (en) | 1977-07-21 | 1978-07-20 | Substituted 1-piperazinyl-triazolo-thieno-1,4-diazepines |
| HU78BO1726A HU176485B (en) | 1977-07-21 | 1978-07-20 | Process for producing new substituted 1-piperasinyl-triasoln-thieno-1,4-diazepines |
| DK325178A DK150306C (en) | 1977-07-21 | 1978-07-20 | METHOD OF ANALOGUE FOR PREPARING SUBSTITUTED 1-PIPERAZINYL-4H-S-TRIAZOLO (3,4-C) THIENO (2,3-E) 1,4-DIAZEPINES OR ACID ADDITION SALTS THEREOF |
| AU38209/78A AU515885B2 (en) | 1977-07-21 | 1978-07-20 | SUBSTITUTED 1-PIPERAZINO-TRIAZOLO-THIENO-l, 4-DIAZEPINES |
| SE7808019A SE439920B (en) | 1977-07-21 | 1978-07-20 | SUBSTITUTED 1-PIPERAZINYL-TRIAZOLO-TIENO-1,4-DIAZEPINES AND PHARMACEUTICAL PREPARATIONS OF |
| PT68330A PT68330A (en) | 1977-07-21 | 1978-07-20 | NEW SUBSTITUTED 1-PIPERAZINYL-TRIAZOLOTHIENO-1,4-DIAZEPINE |
| NZ187915A NZ187915A (en) | 1977-07-21 | 1978-07-20 | 6-phenyl-1-piperazino-4h-s-triazolo(3,4-c)-thieno-(2,3-e)(1,4)diazepines |
| DD78206830A DD137934A5 (en) | 1977-07-21 | 1978-07-20 | METHOD FOR THE PRODUCTION OF NEW SUBSTITUTED 1-PIPERAZINYL-4H-S-TRIAZOLO-SQUARE BRACKET TO 3.4C SQUARE BRACKET TO-THIENO SQUARE BRACKET TO 2.3E SQUARE BRACKET TO-1.4-DIAZEPINE |
| CA307,798A CA1087182A (en) | 1977-07-21 | 1978-07-20 | Substituted 1-piperazinyl-triazolo-thieno-1,4- diazepines |
| IE1456/78A IE47336B1 (en) | 1977-07-21 | 1978-07-20 | Substituted 1-perpazinyl-triazolo-thieno-1,4-diazepines |
| FR7821744A FR2398070A1 (en) | 1977-07-21 | 1978-07-21 | NEWS 1-PIPERAZINYL-TRIAZOLO-THIENO-1,4-DIAZEPINES SUBSTITUTES AND THEIR APPLICATION AS MEDICINAL PRODUCTS |
| ES472812A ES472812A1 (en) | 1977-07-21 | 1978-08-24 | Substituted 1-piperazinyl-4H-s-triazolo (3,4-c)thieno(2,3-e)1,4-diazepines, process for their preparation and medicaments containing them. |
| SU792746903A SU793402A3 (en) | 1977-07-21 | 1979-04-04 | Method of preparing 1-piperazinyl-4h-s-triazolo-/3,4c/-thieno-/2,3e/-2,4-diazepin derivatives |
| SU792744749A SU784778A3 (en) | 1977-07-21 | 1979-04-04 | Method of preparing substituted 1-piperazinyl-4h-s-triazolo-/3,4-c/ thieno /2,3-e/ 1,4-diazepins |
| AT614879A AT363951B (en) | 1977-07-21 | 1979-09-19 | METHOD FOR PRODUCING NEW SUBSTITUTED 1-PIPERAZINYL-TRIAZOLOTHIENO-1,4-DIAZEPINE AND ITS SALTS |
| CS801311A CS209898B2 (en) | 1977-07-21 | 1980-02-26 | Method of making the new substituted 1-piperaziyl-4h-s-triazolo/ 3,4c/ thieno /2,3e/ -1,4-diazepines |
| CS801312A CS209899B2 (en) | 1977-07-21 | 1980-02-26 | Method of making the new substituted 1-piperazinyl-4h-s-triazolo /3,4c/ thieno/2,3e/ -1,4-diazepines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772732921 DE2732921A1 (en) | 1977-07-21 | 1977-07-21 | 1-Piperazino-triazolo-thieno-diazepine derivs. - useful as anxiolytics, tranquillisers, sedatives and neuroleptics |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2732921A1 true DE2732921A1 (en) | 1979-02-08 |
Family
ID=6014485
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19772732921 Withdrawn DE2732921A1 (en) | 1977-07-21 | 1977-07-21 | 1-Piperazino-triazolo-thieno-diazepine derivs. - useful as anxiolytics, tranquillisers, sedatives and neuroleptics |
Country Status (3)
| Country | Link |
|---|---|
| BE (1) | BE869136A (en) |
| DE (1) | DE2732921A1 (en) |
| SU (1) | SU784778A3 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5895785A (en) * | 1987-10-20 | 1999-04-20 | Ruth Korth | Treatment and prevention of disorders mediated by LA-paf or endothelial cells |
| EP0540766A1 (en) * | 1991-11-04 | 1993-05-12 | Korth, Ruth-Maria, Dr. med | Treatment of eosinophil-mediated diseases with Paf antagonists and procedure for determining their efficacy. |
| ATE221779T1 (en) * | 1991-11-04 | 2002-08-15 | Ruth-Maria Korth | TREATMENT AND PREVENTION OF ELEVATED LYSO-PAF LEVELS-MEDIATED MENTAL DISEASES USING PAF ANTAGONISTS |
-
1977
- 1977-07-21 DE DE19772732921 patent/DE2732921A1/en not_active Withdrawn
-
1978
- 1978-07-19 BE BE189395A patent/BE869136A/en not_active IP Right Cessation
-
1979
- 1979-04-04 SU SU792744749A patent/SU784778A3/en active
Also Published As
| Publication number | Publication date |
|---|---|
| SU784778A3 (en) | 1980-11-30 |
| BE869136A (en) | 1979-01-19 |
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