CS224926B1 - The 6,11-dihydrodibenzo /b,e/thiepine-11-carboxamide - Google Patents
The 6,11-dihydrodibenzo /b,e/thiepine-11-carboxamide Download PDFInfo
- Publication number
- CS224926B1 CS224926B1 CS377682A CS377682A CS224926B1 CS 224926 B1 CS224926 B1 CS 224926B1 CS 377682 A CS377682 A CS 377682A CS 377682 A CS377682 A CS 377682A CS 224926 B1 CS224926 B1 CS 224926B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- thiepine
- dihydrodibenzo
- carboxamide
- mice
- dose
- Prior art date
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- KWMIYIVKXATREY-UHFFFAOYSA-N 6,11-dihydrobenzo[c][1]benzothiepine-11-carboxamide Chemical compound C1SC2=CC=CC=C2C(C(=O)N)C2=CC=CC=C21 KWMIYIVKXATREY-UHFFFAOYSA-N 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 239000001961 anticonvulsive agent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 231100000111 LD50 Toxicity 0.000 description 2
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 231100000925 very toxic Toxicity 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Látka vzorce I podle vynálezu se vyznačuje protikřečovou aktivitou, má tedy vlastnosti léčiva použitelného proti epilepsii. V testu na myších je velmi málo jedovatá; orální dávka 2 g/kg způsobuje úhyn pouze 20 % myší. Střední letální dávka LD^q je tedy vyšší než 2 g/kg. Látka zabraňuje výskytu křečí u myší vyvolávaných pentetrazolem a rovněž snižuje mortalitu myší po pentetrazolu; střední účinná protikřečová dávka, PD^q je 140 mg/kg p.o. Dávka zabraňující mortalitě u 50 % zvířat se pohybuje mezi 50 a 100 mg/kg p.o. V testu nikotinových křečí při intraperitoneálním podání u myší je střední účinná dávka PD^0 rovna 214 mg/kg. V testu maximálního elektrošoku u myší je při orálním podání střední účinná dávka zabraňující křečím PD^0 = 116 mg/kg. Látka je tedy účinnější než některá běžně užívaná antikonvulsiva, např. fenytoin.The compound of the formula I according to the invention is characterized by anticonvulsant activity and thus has the properties of a medicament useful against epilepsy. It is very toxic in the mouse test; an oral dose of 2 g / kg causes death in only 20% of the mice. Thus, the median lethal dose of LD 50 is greater than 2 g / kg. The agent prevents seizures in pentetrazole-induced mice and also reduces the mortality of mice after pentetrazole; mean effective anticonvulsant dose, PD ^ q is 140 mg / kg po The mortality prevention dose in 50% of the animals is between 50 and 100 mg / kg after the intraperitoneal administration in mice, the mean effective dose PD4 0 is 214 mg / kg. In the maximal electroshock test in mice when administered orally median effective dose preventing convulsions PD ^ 0 = 116 mg / kg. Thus, the agent is more effective than some commonly used anticonvulsants such as phenytoin.
Látku vzorce I lze získat ze známé kyseliny 6,11-dihydrodibenzo(b,e)thiepin-11-karboxylové (Rajšner M., Bártl V., Šindelář K., Svátek E., Holubek J., Metyš J., Protiva M.: Collect. Czech.Chem.Commun. 44. 2536, 1979) tak, jax je to popsáno v příkladu provedení. Spočívá to v reakci jmenované kyseliny s thionylchloridem a v následujícím působení vodného amoniaku na vzniklý, avšak v čistém stavu neisolovaný chlorid jmenova2 né kyseliny.The compound of formula I can be obtained from the known 6,11-dihydrodibenzo (b, e) thiepine-11-carboxylic acid (Rajšner M., Bartl V., Šindelář K., Svátek E., Holubek J., Metés J., Protiva M Chem. Commun. 44, 2536 (1979) as described in the exemplary embodiment. This consists in the reaction of the said acid with thionyl chloride and subsequent treatment with aqueous ammonia on the formed, but not pure, chloride of the said acid.
224 926224 926
Identita látky I podle vynálezu byla zajištěna analysou v Ί a dále pomocí IC a H NMR spektra. Přípravu lze provést tímto způsobem:The identity of the compound I according to the invention was ensured by analysis in v and further by means of the IC and 1 H NMR spectra. The preparation can be carried out as follows:
Ke směsi 3,1 g 6,11-dihydrodibenzo(b,e)thiepin-11-karbcxylové kyseliny (literatura citována) a 20 ml benzenu se přidáTo a mixture of 3.1 g of 6,11-dihydrodibenzo (b, e) thiepine-11-carboxylic acid (literature cited) and 20 ml of benzene is added
2,9 g thionylchloridu a směs se vaří 5 h pod zpětným chladičem. Benzen a přebytečný thionylchlorid se odpaří za sníženého tlaku, zbytek se rozpustí ve 3 ml acetonu a roztok se zvolna přidá ke 20 ml míchaného koncentrovaného hydroxidu amonného. Po stání přes noc se vyloučený pevný produkt odsaje a matečný louh se zpracuje částečným odpařením. Ze zbytku se vyloučí II. produkt. Celkem se získá 2,4 g (75 %) téměř čistého produktu tajícího při 177,5 až 179,5 °C. Jedinou rekrystalisací z ethanolu se získá zcela čisté látka tající při 179 až 180 °C.2.9 g of thionyl chloride and the mixture was refluxed for 5 h. The benzene and excess thionyl chloride are evaporated under reduced pressure, the residue is dissolved in 3 ml of acetone and the solution is slowly added to 20 ml of stirred concentrated ammonium hydroxide. After standing overnight, the precipitated solid product is filtered off with suction and the mother liquor is treated by partial evaporation. II. product. A total of 2.4 g (75%) of an almost pure product melting at 177.5-179.5 ° C was obtained. A single recrystallization from ethanol yields a pure substance melting at 179-180 ° C.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS377682A CS224926B1 (en) | 1982-05-21 | 1982-05-21 | The 6,11-dihydrodibenzo /b,e/thiepine-11-carboxamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS377682A CS224926B1 (en) | 1982-05-21 | 1982-05-21 | The 6,11-dihydrodibenzo /b,e/thiepine-11-carboxamide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS224926B1 true CS224926B1 (en) | 1984-02-13 |
Family
ID=5378821
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS377682A CS224926B1 (en) | 1982-05-21 | 1982-05-21 | The 6,11-dihydrodibenzo /b,e/thiepine-11-carboxamide |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS224926B1 (en) |
-
1982
- 1982-05-21 CS CS377682A patent/CS224926B1/en unknown
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