CS201998B1 - Carbamate derived from piperazinalkanol of dibenzo/b,f/tthiepine serie - Google Patents
Carbamate derived from piperazinalkanol of dibenzo/b,f/tthiepine serie Download PDFInfo
- Publication number
- CS201998B1 CS201998B1 CS441479A CS441479A CS201998B1 CS 201998 B1 CS201998 B1 CS 201998B1 CS 441479 A CS441479 A CS 441479A CS 441479 A CS441479 A CS 441479A CS 201998 B1 CS201998 B1 CS 201998B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- dibenzo
- tthiepine
- piperazinalkanol
- serie
- formula
- Prior art date
Links
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 title claims description 4
- 150000003839 salts Chemical class 0.000 claims description 3
- 150000003551 thiepines Chemical class 0.000 claims description 2
- 125000005605 benzo group Chemical group 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 235000005985 organic acids Nutrition 0.000 claims 1
- ZCMLTJOUQXELAE-UHFFFAOYSA-N propyl n-octylcarbamate Chemical compound CCCCCCCCNC(=O)OCCC ZCMLTJOUQXELAE-UHFFFAOYSA-N 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- DYQFCTCUULUMTQ-UHFFFAOYSA-N 1-isocyanatooctane Chemical compound CCCCCCCCN=C=O DYQFCTCUULUMTQ-UHFFFAOYSA-N 0.000 description 2
- -1 3- [4- (8-methylthio-10,11-dihydrodibenzo [b, f] thiepin-10-yl) piperazino] propyl Chemical group 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 229940125683 antiemetic agent Drugs 0.000 description 2
- 239000002111 antiemetic agent Substances 0.000 description 2
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 2
- 229960004046 apomorphine Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003176 neuroleptic agent Substances 0.000 description 2
- 230000000701 neuroleptic effect Effects 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-M oxalate(1-) Chemical compound OC(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-M 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- BISQTCXKVNCDDA-UHFFFAOYSA-N thiepine Chemical compound S1C=CC=CC=C1 BISQTCXKVNCDDA-UHFFFAOYSA-N 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000003354 anti-apomorphinic effect Effects 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical compound O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Tento vynález se týká karbamátu odvozeného od piperazinoalkanolu dibenzo(b, f)thiepinové řady vzorce I,This invention relates to a carbamate derived from piperazinoalkanol dibenzo (b, f) of the thiepine series of formula I,
tj. 3-/4-(8-methylthio-10, 11-dihydrodibenzo/ b, f/thiepin-10-yl)-piperazino/propyl-N-oktylkarbamátu, jakož i jeho solí.ie 3- [4- (8-methylthio-10,11-dihydrodibenzo [b, f] thiepin-10-yl) piperazino] propyl N-octylcarbamate, and salts thereof.
Látka vzorce I je dlouhodobě působící antiemetikum, které současně nemá vlastnosti neuroleptika. Bylo to zjištěno při testování látky na antiapomorfinovou účinnost u psů a krys, přičemž látka byla podávána intramuskulárně ve formě 2,5 % roztoku base vzorce I v triglyceridu miglyolu. V testu antagonisace apomorfinového zvracení u psů byla látka podána v jediné dávce 5 mg/kg i. m, I když 100 % blokády emese nebylo dosaženo ani v prvním intervalu po podání (tj. po 7 dnech), přetrvávala blokáda emese u části psů ve skupině déle než 4 týdny a u jednoho psa ze skupiny 6 zvířat trvala dokonce déle než 6 týdnů. Naproti tomu dávka 25 mg/kg i. m. u krys nepůsobila inhibičně vůči apomorfinovým stereotypiím při hodnocení za 24 a 48 hodin po podání.The compound of formula (I) is a long-acting antiemetic agent which, at the same time, does not have the properties of a neuroleptic. This was found by testing the compound for antiapomorphine activity in dogs and rats, administered intramuscularly as a 2.5% solution of the base of Formula I in the triglyceride miglyol. In the apomorphine vomiting antagonism test in dogs, the compound was administered at a single dose of 5 mg / kg i.m., although 100% emesis block was not achieved even in the first interval after administration (i.e. after 7 days) the group lasted more than 4 weeks and in one dog from the group of 6 animals lasted even more than 6 weeks. In contrast, a dose of 25 mg / kg i.m. in rats did not inhibit apomorphine stereotypes when evaluated at 24 and 48 hours after administration.
Z právě uvedeného vyplývá, že látka vzorce I je vhodná k zábraně zvracení různého původu, přičemž není nutné se obávat vedlejších extrapyramidových reakcí, jako při použití neuroleptických antiemetik.It follows from the above that the compound of formula I is suitable for preventing vomiting of various origins, without the need to be afraid of side-effects of extrapyramidal reactions, such as when using neuroleptic antiemetics.
V příkladu provedení je popsán způsob přípravy látky vzorce I, který spočívá v reakci 10-/'4-(3-hydroxypropyl) piperaziho/-8-methyl-thio-10,11-diihydrodibenzo(b,f )thiepinu (Jílek J. O. a spol., Collect. Czěéh. Chem. Commun. 36, 2226, 1971) s oktylisokyanátem (Vološin A. I. a spol., Ž. Prikl.Chim· [Lenin grád] 37,1578, 1964) ve vroucím toluenu.In an exemplary embodiment, a process for the preparation of a compound of formula I is described which comprises reacting 10 - [4- (3-hydroxypropyl) piperazi] -8-methylthio-10,11-diihydrodibenzo (b, f) thiepine (Rye JO and Chem. Commun., 36, 2226, 1971) with octyl isocyanate (Voloshin AI et al., J. Chim · [Lenin Grad] 37, 1578, 1964) in boiling toluene.
Karbamát vzorce I je viskosní olej ovitá kapalina basického charakteru. K jeho charakterisači· se hodí infračervené a lH-NMR spektrum. Neutralisací kyselinami poskytuje krystalické soli, z nichž bis(hydrogenoxalát) taje v čistém stavu při 143 až 148 °C (krystaly z ethanolu).The carbamate of formula I is a viscous, oily liquid of basic nature. Infrared and 1 H-NMR spectra are suitable for its characterization. Acid neutralization yields crystalline salts of which the bis (hydrogen oxalate) melts in a pure state at 143-148 ° C (ethanol crystals).
Příklad provedení:Example:
Směs 9,5 g solvátu base 10-/4~(3-hydroxy~ propyl) piperazino, -8-methylthio-ÍO, ll-di201998 hydrodíbénzo(b,f)thiepinu s molekulou benzenu (Jílek J. O. a spol., Collect. Czech. Chem. Commun. 38, 1190, 1973), 80 ml toluenu a 5,0 g oktylisokyanátu se vaří 3 hodiny pod zpětným chladičem a odpaří ve vakuu. Zbytek se rozpustí v 70 ml 80 % vodného ethanolu a neutralisuje se 6,3 g dihydrátu kyseliny oxalové. Stáním a chlazením vykrystaluje 8,4 g (58 %) bis(hydrogenoxalátu) base vzorce I, t. t. 143 až 148 °C (ethanol). Rozkladem čistého oxalátu zředěným vodným amoniakem a extrakcí benzenem se získá čistá olejovitá base vzorce I, které lze použít k změření spekter i k přípravě lékových forem.A mixture of 9.5 g of the base 10- / 4- (3-hydroxypropyl) piperazino, -8-methylthio-10,11-di201998 hydrobenzene (b, f) thiepine solvate with a benzene molecule (Jílek JO et al., Collect. Chem. Commun. 38, 1190 (1973), 80 ml of toluene and 5.0 g of octyl isocyanate are refluxed for 3 hours and evaporated in vacuo. The residue is dissolved in 70 ml of 80% aqueous ethanol and neutralized with 6.3 g of oxalic acid dihydrate. On standing and cooling, 8.4 g (58%) of the bis (hydrogen oxalate) base of the formula I crystallized, m.p. 143 DEG-148 DEG C. (ethanol). Decomposition of the pure oxalate with dilute aqueous ammonia and extraction with benzene gives a pure oily base of formula I which can be used to measure the spectra as well as to prepare dosage forms.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS441479A CS201998B1 (en) | 1979-06-27 | 1979-06-27 | Carbamate derived from piperazinalkanol of dibenzo/b,f/tthiepine serie |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS441479A CS201998B1 (en) | 1979-06-27 | 1979-06-27 | Carbamate derived from piperazinalkanol of dibenzo/b,f/tthiepine serie |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS201998B1 true CS201998B1 (en) | 1980-12-31 |
Family
ID=5386832
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS441479A CS201998B1 (en) | 1979-06-27 | 1979-06-27 | Carbamate derived from piperazinalkanol of dibenzo/b,f/tthiepine serie |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS201998B1 (en) |
-
1979
- 1979-06-27 CS CS441479A patent/CS201998B1/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1470125C3 (en) | 4-oxo-13,8-triazaspiro [4.5] decane | |
| Cook et al. | Structure-activity studies of 2, 3, 4, 4a, 5, 9b-hexahydroindeno [1, 2-c] pyridines as antispermatogenic agents for male contraception | |
| CS201998B1 (en) | Carbamate derived from piperazinalkanol of dibenzo/b,f/tthiepine serie | |
| DE1770242A1 (en) | Dibenzothiazepine derivatives and processes for their preparation | |
| FI57757C (en) | FRAMEWORK FOR THERAPEUTIC ADMINISTRATION OF THERAPEUTIC THERAPEUTIC | |
| CH651303A5 (en) | BASIC DERIVATIVES OF TRICYCLIC COMPOUNDS AND METHOD FOR THEIR PRODUCTION. | |
| EP0273168A1 (en) | Triazaspirodecanylmethylindolone derivatives | |
| EP0000716A2 (en) | Pyrrolo(2,1-b)(3)benzazepine derivatives, process for their preparation and pharmaceutical compositions containing them | |
| US5446152A (en) | Heterocyclic compounds active in gastro-intestinal pathologies | |
| CH644126A5 (en) | 4-PHENYL-THIENO- (2,3-C) -PIPERIDINE, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS. | |
| US3108997A (en) | Morpholino lower alkanoyl xylidides and toluidides | |
| DE2252806A1 (en) | TRICYCLIC LINKS | |
| DE2705639A1 (en) | PROPYLENE DIAMINES, THE METHOD OF MANUFACTURING THEM AND MEDICINAL PRODUCTS CONTAINING THEM | |
| CS237484B1 (en) | 11-piperazino-6,11-dihydrodibenzo (b, e) thiepines and their salts | |
| EP0180889B1 (en) | 3-amino-2,3-dihydro-1-benzoxepine compounds, process for their preparation and medicaments containing these compounds | |
| DE1568104A1 (en) | Process for the preparation of tricyclic N-alkylated derivatives of acetamide | |
| HU181441B (en) | Process for producing substituted quinolizidine and indolizidine derivatives | |
| EP0189310A2 (en) | N-Substituted 2-chloro-7-fluoro-10-piperazino-10,11-dihydrodibenzo (b,f) thiepins, their acid addition salts and processes for the preparation thereof | |
| SE441447B (en) | 2-HYDROXI-5- / 1-HYDROXI-2- / 4- (2-OXO-1-BENZIMIDAZOLINYL) -PIPERIDINO / ETHYL / BENZOIC ACID DERIVATIVE AND SET TO PREPARE THESE | |
| DE3447730A1 (en) | PYRAZOLOPYRIDE INDEVICES | |
| CS197190B1 (en) | 2-Methyl-10-piperazino-10,11-dihydrodibenzo (b, f) thiepines | |
| DE1695731A1 (en) | New organic compounds | |
| GB1602087A (en) | 2,3-diphenylchromone derivatives and their preparation and therapeutic applications | |
| DE2601540A1 (en) | ACETIDE DERIVATIVES, METHOD OF MANUFACTURING AND PHARMACEUTICAL PRODUCTS CONTAINING THEM | |
| CS211104B1 (en) | Aminoketone Thioxanthene Series |