CS224988B1 - Derivát oktahydropyrrolo(l,2-a)pyrazinu a jeho methansulfonát - Google Patents
Derivát oktahydropyrrolo(l,2-a)pyrazinu a jeho methansulfonát Download PDFInfo
- Publication number
- CS224988B1 CS224988B1 CS604682A CS604682A CS224988B1 CS 224988 B1 CS224988 B1 CS 224988B1 CS 604682 A CS604682 A CS 604682A CS 604682 A CS604682 A CS 604682A CS 224988 B1 CS224988 B1 CS 224988B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- pyrazine
- octanehydropyrrole
- methansulphonate
- derivate
- methanesulfonate
- Prior art date
Links
- GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical compound CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 title description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 10
- FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical class C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 claims description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 1
- 208000009132 Catalepsy Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010047853 Waxy flexibility Diseases 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000002903 catalepsic effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Vynález se týká nového derivátu oktahydropyrrolo(1,2-a)pyrazinu vzorce I
a jeho methansulfonátu. Látce I přísluší název 2-chlor-11-/oktahydropyrrolo(1,2-a)pyrazin-2-yl/-10,11-dihydrodibenzo(b,f)thiepinu. Tato látka a její methansulfonát jsou newroleptiky použitelnými v therapii psychos schizofrenního typu. Je to doloženo vlast nostmi zjištěnými v testech na pokusných zvířatech.
Testován byl methansulfonát látky I, při^čemž uváděné dávky jsou přepočty na basi. Akutní toxicita na myších, LDjq » 34 mg/kg i.v. Diskoordinační účinek v testu rotující tyčky na myších, ED^q (střední účinná dávka vyvolávající ataxii u 50 % zvířat) je 0,45 mg/kg i.v. Kataleptický účinek u krys, ED^q (střední účinná dávka vyvolávající katalepsii u 50 % zvířat) je 3,6 mg/kg i.p.
Látku vzorce I lze připravit substituční reakcí 2,11-dichlor-10,11-dihydrodibenzo(b,f)thiepinu (Jílek J.O. a spol., Collect.Czech.Chem.Commun. 33. 1θ31, 1968) s oktahydropyrrolo(1,2-a)pyrazinem /1,4-diazabicyklo(4,3,0)nonanem/ (Razarova L.S. a spol., Chim.-Parm.Žurnál 10(1), 88, 1976) ve vroucím chloroformu. Produkt má dvě centra chirality, takže lze předpokládat vznik stereoisomerní směsi. Base sice dobře krystaluje, avšak její NMR spektrum není dobře rozlišené, což naznačuje přítomnost ~ίτ
224 988 obou stereoisomerů. Neůtralisací kyselinou methansulfonovou se získá amorfní methansulfonát, který je výborně rozpustný ve vodě a vhodný k provádění farmakologických testů i k výrobě lékových forem. Látka vzorce I se tedy připraví takto :
Směs 2,8 g 2,11-dichlor-10,11-dihydrodibenzo(b,f)thíepinu,
1,9 g oktahydropyrrolo(1,2-a)pyrazinu a 4 ml chloroformu se vaří 7 h pod zpětným chladičem. Potom se odpaří ve vakuu, zbytek se smísí s 30 ml vody a 5 ml hydroxidu amonného a extrahuje se benzenem. Extrakt se protřepe s 10 ml 3M-HC1, vyloučený hydrochlorid se zfiltruje, promyje se benzenem a suspenduje se v 30 ml vo dy. Suspense se zalkalisuje 10 ml hydroxidu amonného a base se isoluje extrakcí benzenem. Zpracováním extraktu se získá 2,55 g (69 %) sklovitého produktu, který krystaluje z ethanolu, t.t.
145 až 150 °C. Neůtralisací této krystalické base (700 mg) methansulfonovou kyselinou (180 mg) ve 3 ml ethanolu a odpařením roztoku se získá 880 mg amorfního methansulfonátu, který je výborně rozpustný ve vodě a vhodný k provádění farmakologických testů.
Claims (1)
- PŘEDMĚT VYNALEZU224 988-JDerivát oktahydropyrrolo(1,2-a)pyrazinu vzorce I a jeho methaneulfonát.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS604682A CS224988B1 (cs) | 1982-08-17 | 1982-08-17 | Derivát oktahydropyrrolo(l,2-a)pyrazinu a jeho methansulfonát |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS604682A CS224988B1 (cs) | 1982-08-17 | 1982-08-17 | Derivát oktahydropyrrolo(l,2-a)pyrazinu a jeho methansulfonát |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS224988B1 true CS224988B1 (cs) | 1984-02-13 |
Family
ID=5406617
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS604682A CS224988B1 (cs) | 1982-08-17 | 1982-08-17 | Derivát oktahydropyrrolo(l,2-a)pyrazinu a jeho methansulfonát |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS224988B1 (cs) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996018630A1 (en) * | 1994-12-12 | 1996-06-20 | Allelix Biopharmaceuticals Inc. | Bicyclic nonane and decane compounds having dopamine receptor affinity |
-
1982
- 1982-08-17 CS CS604682A patent/CS224988B1/cs unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996018630A1 (en) * | 1994-12-12 | 1996-06-20 | Allelix Biopharmaceuticals Inc. | Bicyclic nonane and decane compounds having dopamine receptor affinity |
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