CH548408A - S-triazolo (4,3-a) (1,4) benzodiazepines - as sedatives, hypnotics, tranquillisers, muscle relaxants - Google Patents
S-triazolo (4,3-a) (1,4) benzodiazepines - as sedatives, hypnotics, tranquillisers, muscle relaxantsInfo
- Publication number
- CH548408A CH548408A CH325472A CH325472A CH548408A CH 548408 A CH548408 A CH 548408A CH 325472 A CH325472 A CH 325472A CH 325472 A CH325472 A CH 325472A CH 548408 A CH548408 A CH 548408A
- Authority
- CH
- Switzerland
- Prior art keywords
- triazolo
- formula
- benzodiazepines
- nitro
- compound
- Prior art date
Links
- 239000000932 sedative agent Substances 0.000 title description 3
- 239000003326 hypnotic agent Substances 0.000 title description 2
- 230000000147 hypnotic effect Effects 0.000 title description 2
- 229940125723 sedative agent Drugs 0.000 title description 2
- LGNWUMGEJQAWQD-UHFFFAOYSA-N 1h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical class N1=CC2=CC=CC=C2N2CN=NC2=C1 LGNWUMGEJQAWQD-UHFFFAOYSA-N 0.000 title 1
- 229940035363 muscle relaxants Drugs 0.000 title 1
- 239000003158 myorelaxant agent Substances 0.000 title 1
- -1 tranquillisers Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- IZYKFSZYKIUTTE-UHFFFAOYSA-N 5-(2-chlorophenyl)-7-nitro-1,3-dihydro-1,4-benzodiazepine-2-thione Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=S)CN=C1C1=CC=CC=C1Cl IZYKFSZYKIUTTE-UHFFFAOYSA-N 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 229940049706 benzodiazepine Drugs 0.000 claims description 2
- 150000001557 benzodiazepines Chemical class 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical compound C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 abstract description 2
- 229910052794 bromium Inorganic materials 0.000 abstract description 2
- 229910052801 chlorine Inorganic materials 0.000 abstract description 2
- 229910052731 fluorine Inorganic materials 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 2
- 229960003529 diazepam Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 1
- XJRGLCAWBRZUFC-UHFFFAOYSA-N clonazolam Chemical compound C12=CC([N+]([O-])=O)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl XJRGLCAWBRZUFC-UHFFFAOYSA-N 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229960005152 pentetrazol Drugs 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Title cpds. have formula (where Hal is F, Cl or Br) and are prepd. by reacting a benzoidiazepin-2-thione with acetylhydrazine.
Description
Die vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung von 8-Nitro-6-(o-halogenphenyl)-l -methyl -4H-s-triazolo[4,3-a] 11,4)benzodiazepinen der folgenden Formel
EMI1.1
worin der Substituent Hal ein Halogenatom mit der Atomnummer bis zu 35 ist, nämlich Fluor, Chlor oder Brom. Die erfindungsgemäss erhältlichen Verbindungen können in ihre pharmakologisch annehmbaren Säureadditionssalze überführt werden. Die erfindungsgemäss herstellbaren Verbindungen sind insbesondere nützlich als hypnotische Mittel, als Sedativa, Beruhigungsmittel und als Entspannungsmittel für die Muskulatur. Die neuen Verbindungen weisen eine vor allem niedrige Giftigkeit auf.
Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man eine Verbindung der Formel
EMI1.2
worin Hal die weiter oben angegebene Bedeutung hat, mit einer Verbindung der Formel
EMI1.3
kondensiert.
Die Herstellung der Ausgangsverbindungen des erfindungsgemässen Verfahrens wurde beschrieben von (A) L.H. Sternbach et al. im J. Med. Chem. 6, 261 (1963) und (B) im U.S. Patent 3 422091. Diese Ausgangsverbindungen werden vorzugsweise hergestellt, indem man ein entsprechendes, bekanntes 7-Nitro- I ,3-dihydro-5-(o-halogenphenyl)-2H-1 ,4-benzodi- azepin-2-on, dessen Herstellung in (A) beschrieben wurde, mit Phosphorpentasulfid in Pyridin etwa 45 Minuten lang erhitzt beschrieben in (B). Diese Umsetzung wurde von J. A. Archer et al. im J. Org. Chem. 29 (1963) veröffentlicht; Präparat 1: 1,3-Dihydro-7- 1,3-Dihydro-7-nitro-5-(o-chlorphenyl)-2H-1,4- -benzodiazepin-2-on.
Man gab eine Lösung, die aus 1,7 g (0,017 Mol) Kaliumnitrat in 5 ml konzentrierter Schwefelsäure bestand, tropfenweise zu einer gerührten Lösung von 4,2 g (0,015 Mol) 1,3-Di- hydro.5-(o-chlorphenyl) -2H-1 ,4-benzodiazepin-2-on in 15 ml konzentrierter Schwefelsäure. Man erhitzte die Mischung auf einem Dampfbad bei einer Temperatur von 450 bis 50"C und rührte etwa 3 Stunden lang. Dann kühlte man ab und gab auf Eis. Nach der Neutralisation mit Ammoniak trennte man den erhaltenen Niederschlag ab, es wurde mit Wasser gewaschen, in Methylenchlorid gelöst und über Kaliumcarbonat getrocknet. Nach dem Abfiltrieren dampfte man die erhaltene Lösung zur Trockne eine und erhielt 4.5 g einer bräunlichen, kristallinen Verbindung.
Die erhaltene Verbindung wurde kristallisiert, indem man in 300 ml Methylenchlorid löste, auf ein Volumen von 50 ml konzentrierte und schliesslich abkühlte. Man erhielt 3 bis 5 g (71%) einer gelblichen, kristallinen Verbindung, die einen Schmelzpunkt von 232 bis 235"C hatte. (Bekannt ist ein Schmelzpunkt von 2380 bis 240"C).
Die herstellten IR- und NMR-Spektren bestätigten die Struktur.
Präparat 2: 1,3-Dihydro-7-nitro-5-(o-chlorphenyl)-2H-1,4- -benzodiazepin-2-thion.
Eine Mischung, die aus 15 g (0,047 Mol) 1,3-Dihydro-7 -nitro-5-(o-chlorphenyl)-2H- 1 ,4-benzodiazepin-2-on und 14 g (0,064 Mol) Phosphorpentasulfid in 100 ml Pyridin bestand, wurde schnell erhitzt und am Rückfluss während 45 Minuten gehalten. Man verdampfte die erhaltene dunkle Lösung im Vakuum zur Trockne. Der Rückstand wurde mit 200 ml einer Natriumchloridlösung behandelt und dann mit drei Portionen von je 500 ml Methylenchlorid extrahiert. Man wusch die Methylenchloridlösung mit Wasser und trocknete mit Kaliumcarbonat. Nach der Filtration und nach dem Eindampfen im Vokuum zur Trockne löste man den erhaltenen Rückstand in 100 ml Toluol und dampfte abermals zur Trockne ein, um das noch vorhandene Pyridin zu entfernen. Man löste den Rückstand in 1 Liter Methanol (Darco) und filtrierte die heisse Lösung.
Die äthanolische Lösung wurde auf ein Volumen von 150 ml konzentriert und dann auf eine Temperatur von 0 C abgekühlt. Man erhielt 10 g (66%) einer gelben, kristallinen Verbindung, die einen Schmelzpunkt von 2190 bis 221 OC aufwies (unter Zersetzung).
Analyse für ClsH,oCIN302S: Ber.: C 54,29 H 3,02 N 12,70 Cl 10,69 S 9,65 Gef.: C 54,51 H 2,92 N 12,63 Cl 10,63 S 9,52
Beispiel 8-Nitro-6-(o-chlorphenyl)-I -methyl-4H-s-triazolo - [4,3-a] [1,4]benzodiazepin
Eine Mischung, die aus 3 g (0,008 Mol) 1,3-Dihydro-7 -nitro-5-(o-chlorphenyl)-2H- 1 ,4-benzodiazepin-2-thion und 2,1 g (0,024 Mol) Acethydrazid in 300 ml normalem Butanol bestand, wurde 16 Stunden lang am Rückfluss erhitzt. Während dieser Zeit leitete man Stickstoff durch die Reaktionsmischung. Man verdampfte anschliessend die Lösung zur Trockne und der Rückstand wurde mit Wasser behandelt, wodurch man 3 g eines orangefarbigen Feststoffs erhielt.
Die erhaltene feste Substanz wurde in 300 ml Isopropylalkohol gelöst, heiss filtriert, auf ein Volumen von 50 ml konzentriert und auf eine Temperatur von 0 eingedampft. Man erhielt 2 g eines gelblichen, kristallinen Produktes. das einen Schmelzpunkt von 2290 bis 231 0C hatte.
Analyse für CITHl2ClNsO2 Ber.: C 57,74 H 3,39 N 19,80 Cl 10,03 Gef.: C 57,42 H 3,48 N 19,56 Cl 9,94
Die erhaltene Verbindung stellt eine äusserst aktive Substanz in allen CNS-Evaluationstesten dar. (Ungefähr 50 bis 100mal mehr aktiv als Diazepam). Diese Verbindung verhält sich während Endmessungen des Sedativen oder hypnotischen Potentials äusserst aktiv (Potenzierung der Pentabarbitualen, Chloroprothixenen und äthanolischen Narkose). Die Verbindung hat ebenfalls eine entspannende Wirkung auf die Muskulatur, eine antikonvulsive Aktivität und stellt ein antagonistisches Mittel bei der Behandlung von sich aggressiv verhaltenden Mäusen dar.
Die Verbindung ist ein antagonistisches Mittel bei durch pentylentetrazol-induzierten Konvulsionen (35mal mehr aktiv als das Diazepam) und sie besitzt einen Endpunkt, welcher mit der anti-anxiolytischen Aktivität in Menschen in einem bestimmten Verhältnis steht.
The present invention relates to a process for the preparation of 8-nitro-6- (o-halophenyl) -l-methyl -4H-s-triazolo [4,3-a] 11,4) benzodiazepines of the following formula
EMI1.1
wherein the substituent Hal is a halogen atom with the atomic number up to 35, namely fluorine, chlorine or bromine. The compounds obtainable according to the invention can be converted into their pharmacologically acceptable acid addition salts. The compounds which can be prepared according to the invention are particularly useful as hypnotic agents, as sedatives, tranquilizers and as relaxants for the muscles. The new compounds are particularly low in toxicity.
The inventive method is characterized in that a compound of the formula
EMI1.2
wherein Hal has the meaning given above, with a compound of the formula
EMI1.3
condensed.
The preparation of the starting compounds of the process according to the invention was described by (A) L.H. Sternbach et al. in J. Med. Chem. 6, 261 (1963) and (B) in U.S. Patent 3,42091. These starting compounds are preferably prepared by adding a corresponding, known 7-nitro-1,3-dihydro-5- (o-halophenyl) -2H-1,4-benzodiazepin-2-one, its preparation described in (A), heated with phosphorus pentasulfide in pyridine for about 45 minutes described in (B). This implementation was described by J. A. Archer et al. published in J. Org. Chem. 29 (1963); Preparation 1: 1,3-Dihydro-7-1,3-Dihydro-7-nitro-5- (o-chlorophenyl) -2H-1,4- -benzodiazepin-2-one.
A solution consisting of 1.7 g (0.017 mol) of potassium nitrate in 5 ml of concentrated sulfuric acid was added dropwise to a stirred solution of 4.2 g (0.015 mol) of 1,3-dihydro.5- (o- chlorphenyl) -2H-1, 4-benzodiazepin-2-one in 15 ml of concentrated sulfuric acid. The mixture was heated on a steam bath at a temperature of 450 to 50 "C and stirred for about 3 hours. It was then cooled and poured onto ice. After neutralization with ammonia, the precipitate obtained was separated off and washed with water. dissolved in methylene chloride and dried over potassium carbonate.After filtering off, the solution obtained was evaporated to dryness and 4.5 g of a brownish, crystalline compound were obtained.
The compound obtained was crystallized by dissolving in 300 ml of methylene chloride, concentrating to a volume of 50 ml and finally cooling. 3 to 5 g (71%) of a yellowish, crystalline compound were obtained which had a melting point of 232 to 235 "C. (A melting point of 2380 to 240" C is known).
The IR and NMR spectra produced confirmed the structure.
Preparation 2: 1,3-Dihydro-7-nitro-5- (o-chlorophenyl) -2H-1,4- -benzodiazepine-2-thione.
A mixture consisting of 15 g (0.047 mol) 1,3-dihydro-7-nitro-5- (o-chlorophenyl) -2H-1, 4-benzodiazepin-2-one and 14 g (0.064 mol) phosphorus pentasulphide in 100 ml of pyridine was heated rapidly and refluxed for 45 minutes. The resulting dark solution was evaporated to dryness in vacuo. The residue was treated with 200 ml of a sodium chloride solution and then extracted with three portions of 500 ml each of methylene chloride. The methylene chloride solution was washed with water and dried with potassium carbonate. After filtration and evaporation to dryness in vacuo, the residue obtained was dissolved in 100 ml of toluene and again evaporated to dryness in order to remove the pyridine still present. The residue was dissolved in 1 liter of methanol (Darco) and the hot solution was filtered.
The ethanolic solution was concentrated to a volume of 150 ml and then cooled to a temperature of 0.degree. 10 g (66%) of a yellow, crystalline compound were obtained which had a melting point of 2190 to 221 ° C. (with decomposition).
Analysis for ClsH, oCIN302S: Calculated: C 54.29 H 3.02 N 12.70 Cl 10.69 S 9.65 Found: C 54.51 H 2.92 N 12.63 Cl 10.63 S 9 , 52
Example 8-Nitro-6- (o -chlorophenyl) -I -methyl-4H-s-triazolo - [4,3-a] [1,4] benzodiazepine
A mixture consisting of 3 g (0.008 mol) 1,3-dihydro-7-nitro-5- (o-chlorophenyl) -2H-1, 4-benzodiazepine-2-thione and 2.1 g (0.024 mol) acethydrazide consisted of 300 ml normal butanol was refluxed for 16 hours. During this time nitrogen was bubbled through the reaction mixture. The solution was then evaporated to dryness and the residue was treated with water to give 3 g of an orange solid.
The solid substance obtained was dissolved in 300 ml of isopropyl alcohol, filtered hot, concentrated to a volume of 50 ml and evaporated to a temperature of 0. 2 g of a yellowish, crystalline product were obtained. which had a melting point of 2290 to 231 0C.
Analysis for CITHl2ClNsO2 Calculated: C 57.74 H 3.39 N 19.80 Cl 10.03 Found: C 57.42 H 3.48 N 19.56 Cl 9.94
The compound obtained is an extremely active substance in all CNS evaluation tests (about 50 to 100 times more active than diazepam). This connection is extremely active during final measurements of the sedative or hypnotic potential (potentiation of the pentabarbituals, chloroprothixenes and ethanolic anesthesia). The compound also has muscle relaxing effects, anticonvulsant activity, and is an antagonistic agent in the treatment of aggressive mice.
The compound is an antagonistic agent in pentylenetetrazole-induced convulsions (35 times more active than the diazepam) and it has an end point which is related to the anti-anxiolytic activity in humans.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH325472A CH548408A (en) | 1969-03-17 | 1972-03-06 | S-triazolo (4,3-a) (1,4) benzodiazepines - as sedatives, hypnotics, tranquillisers, muscle relaxants |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80793369A | 1969-03-17 | 1969-03-17 | |
| US04/872,394 US3987052A (en) | 1969-03-17 | 1969-10-29 | 6-Phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines |
| CH325472A CH548408A (en) | 1969-03-17 | 1972-03-06 | S-triazolo (4,3-a) (1,4) benzodiazepines - as sedatives, hypnotics, tranquillisers, muscle relaxants |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH548408A true CH548408A (en) | 1974-04-30 |
Family
ID=33101600
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH325472A CH548408A (en) | 1969-03-17 | 1972-03-06 | S-triazolo (4,3-a) (1,4) benzodiazepines - as sedatives, hypnotics, tranquillisers, muscle relaxants |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH548408A (en) |
-
1972
- 1972-03-06 CH CH325472A patent/CH548408A/en not_active IP Right Cessation
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