CS224925B1 - The e-11-/3-dimethylaminepropylidene/-6,11-dihydrodibenzo-/b,e/thiepine /4,4-methylen bis /3-hydroxy 2-naphtoate - Google Patents
The e-11-/3-dimethylaminepropylidene/-6,11-dihydrodibenzo-/b,e/thiepine /4,4-methylen bis /3-hydroxy 2-naphtoate Download PDFInfo
- Publication number
- CS224925B1 CS224925B1 CS377582A CS377582A CS224925B1 CS 224925 B1 CS224925 B1 CS 224925B1 CS 377582 A CS377582 A CS 377582A CS 377582 A CS377582 A CS 377582A CS 224925 B1 CS224925 B1 CS 224925B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- hydroxy
- dihydrodibenzo
- thiepine
- dimethylaminepropylidene
- naphtoate
- Prior art date
Links
- BISQTCXKVNCDDA-UHFFFAOYSA-N thiepine Chemical compound S1C=CC=CC=C1 BISQTCXKVNCDDA-UHFFFAOYSA-N 0.000 title description 3
- -1 3-dimethylaminopropylidene Chemical group 0.000 claims description 6
- AQXXZDYPVDOQEE-MXDQRGINSA-N Pyrantel pamoate Chemical compound CN1CCCN=C1\C=C\C1=CC=CS1.C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 AQXXZDYPVDOQEE-MXDQRGINSA-N 0.000 claims 1
- 150000003839 salts Chemical class 0.000 description 8
- 239000000243 solution Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 2
- 229960001393 dosulepin Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- PHTUQLWOUWZIMZ-GZTJUZNOSA-N trans-dothiepin Chemical compound C1SC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 PHTUQLWOUWZIMZ-GZTJUZNOSA-N 0.000 description 2
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102100036988 Cyclin-dependent kinase 2-interacting protein Human genes 0.000 description 1
- 101000737869 Homo sapiens Cyclin-dependent kinase 2-interacting protein Proteins 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Landscapes
- Steroid Compounds (AREA)
Description
Látka vzorce I je novou solí base E-11-(3-dimethylaminopropyl.iden)-6,11-dihydrodibenzoJb,eJthiepinu, známého pod generickými názvy prothiaden, dothiepin, regp. dosulepin. Soli této base se vyznačují vynikající antidepresivní účinností, při čemž hydrochlorid je v široké míře používán v therapeutické praxi (Metyšová J., Metyš J., Votava Z.: Arzneim.-Porsch. JJ, 1039, 1963:The compound of formula (I) is a new base salt of E-11- (3-dimethylaminopropylidene) -6,11-dihydrodibenzo [b], thiepine, known under the generic names hindered, dothiepine, regp. dosulepin. Salts of this base are distinguished by excellent antidepressant activity, the hydrochloride being widely used in therapeutic practice (Metyšová J., Metyš J., Votava Z .: Arzneim.-Porsch. JJ, 1039, 1963:
Rees J.A., Marsh B.D.: 9th Congr. CINP, Paříž, červenec. 1974» J· Pharmacol. Paris J, Suppl. 2, 84, 1974; Int.Pharmacopsychiat.Rees, J.A., Marsh B.D .: 9th Congr. CINP, PARIS, JULY. 1974 J Pharmacol. Paris J Suppl. 2, 84 (1974); Int.Pharmacopsychiat.
chloridu je jeho hořkáva 1cchloride is its bitter 1c
10, 54, 1975). Jistou nevýhodou ve vodě výborně rozpustného hydrohokálně anestetické působení při styku s ústní sliznici·10, 54, 1975). A certain disadvantage of the water-soluble hydro-local anesthetic action in contact with the oral mucosa
Nyní bylo zjištěno, že tyto nepříznivé vlastnosti nemá sůl jmenované base s kyselinou 4,4*-methylenbis(3-hydroxy-2-naftoovou), která je známa též jako kyselina pamoová nebo embonová (viz The Merck Index, 9. vyd., str. 908,· 1976). Tato sůl, která je tvoře224 925 na dvěma molekulami base a jednou molekulou kyseliny je ve vodě minimálně rozpustná, je prakticky bez chuti a nepůsobí místní znecitlivění. Při tom je výborně resorbována ze zažívacího traktu a tudíž vhodná k přípravě lékových forem prothiadenu pro orální použití.It has now been found that the salt of the said base with 4,4 ' -methylenebis (3-hydroxy-2-naphthoic acid), also known as pamoic or embonic acid, does not have these adverse properties (see The Merck Index, 9th ed., p. 908, 1976). This salt, which is 224 925 on two base molecules and one acid molecule is minimally soluble in water, is virtually tasteless and does not cause local anesthesia. In doing so, it is excellently absorbed from the gastrointestinal tract and is therefore suitable for the preparation of dosage forms of prothiadene for oral use.
Sůl vzorce I lze v principu připravit neutralisací base kyselinou. Vzhledem k tomu, že však jsou obě tyto látky nerozpustné ve vodě a produkt , tj. výsledná sůl, je rovněž nerozpustná, představuje přímá neutralisace určitý technický problém. Z toho důvodu je lépe použít podvojné reakce předem připraveného roztoku sodné soli kyseliny 4,4'-methylenbis(3-hydroxy-2-naftoové) s vodným roztokem hydrochloridu E-11-(3-dimethylaminopropyliden)-6,11-dihydrodibenzo|b,e|thiepinu. Žádaná sůl vzorce I se vyloučí jako mikrokrystalická sraženina, která se odsaje, promyje vodou a vysuší. Podle analysy má uvedené složeni.The salt of formula I can in principle be prepared by neutralizing the base with an acid. However, since both are insoluble in water and the product, i.e. the resulting salt, is also insoluble, direct neutralization is a technical problem. For this reason, it is preferable to use the double reactions of a previously prepared solution of sodium 4,4'-methylenebis (3-hydroxy-2-naphthoic acid) with an aqueous solution of E-11- (3-dimethylaminopropylidene) -6,11-dihydrodibenzo [b] hydrochloride. , e | thiepine. The desired salt of formula (I) is precipitated as a microcrystalline precipitate which is filtered off with suction, washed with water and dried. According to analysis, it has said composition.
Příprava látky vzorce I se tedy provede takto: Mícháním rozto-ku 1,6 g hydroxidu sodného ve 120 ml se 7,8 g kyseliny 4,4*-methylenbis(3-hydroxy-2-naftoové) se připraví roztok sodné soli. Zfiltruje se a filtrát se za prudkého míchání zvolna přidá k roztoku 13,2 g hydrochloridu E-1.1-(3~dimethylaminopropyliden)-6,11-dihydrodibenzo{b,ejthiepinu (Rajšner M., Protiva M.: Česk.Parm. 11. 404, 1962; Rajšner M., Svátek E., Metyšová J., Protiva M.: Collect.Czech.Chem.Coramun. 34. 1963, 1969). Vyloučená sůl vzorce I se po 30 min stání odsaje, promyje se vodou a vysuší ve vakuu. Získá se 15,0 g (76 %) monohydrátu soli I obsahující na 1 molekulu kyseliny 2 molekuly base. Produkt taje při 170 °C, při čemž počíná jihnout od 128 °C.Thus, the preparation of the compound of formula (I) is carried out as follows: A solution of sodium salt is prepared by mixing a solution of 1.6 g of sodium hydroxide in 120 ml with 7.8 g of 4,4'-methylenebis (3-hydroxy-2-naphthoic acid). It is filtered and the filtrate is slowly added to a solution of 13.2 g of E-1,1- (3-dimethylaminopropylidene) -6,11-dihydrodibenzo {b, ejthiepine hydrochloride (Rajšner M., Protiva M .: Czech Pharm. 11) under vigorous stirring. 404, 1962; Rajsner M., Sveta E., Metasova J., Protiva M .: Collect.Czech.Chem.Coramun. 34, 1963, 1969). The precipitated salt of formula I is filtered off with suction after standing for 30 minutes, washed with water and dried in vacuo. 15.0 g (76%) of the monohydrate salt I is obtained containing 2 base molecules per molecule of acid. The product melts at 170 ° C, starting to start from 128 ° C.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS377582A CS224925B1 (en) | 1982-05-21 | 1982-05-21 | The e-11-/3-dimethylaminepropylidene/-6,11-dihydrodibenzo-/b,e/thiepine /4,4-methylen bis /3-hydroxy 2-naphtoate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS377582A CS224925B1 (en) | 1982-05-21 | 1982-05-21 | The e-11-/3-dimethylaminepropylidene/-6,11-dihydrodibenzo-/b,e/thiepine /4,4-methylen bis /3-hydroxy 2-naphtoate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS224925B1 true CS224925B1 (en) | 1984-02-13 |
Family
ID=5378810
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS377582A CS224925B1 (en) | 1982-05-21 | 1982-05-21 | The e-11-/3-dimethylaminepropylidene/-6,11-dihydrodibenzo-/b,e/thiepine /4,4-methylen bis /3-hydroxy 2-naphtoate |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS224925B1 (en) |
-
1982
- 1982-05-21 CS CS377582A patent/CS224925B1/en unknown
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