SE174470C1

SE174470C1 -

Info

Publication number: SE174470C1
Authority: SE
Publication date: 1961-01-01

Description

Prioritet begard frail den 1 auuttsti oelt 18 december 1956 (Frankrike) Foreliggande uppfinning hanfor sig till framstallningen av nya fentiazinderivat med den all-manna formeln: /\S /\ II Iil—SO,N(CH,),1 1 A — Z och dcras salter med terapeutiskt anvandbara syror samt deras kvaternara ammoniumderivat. Bland de terapeutiskt anvandbara syrorna kunna omnamnas saltsyra, fosforsyra, salpetersyra; svavelsyra, maleinsyra, fumarsyra, vinsyra, oxalsyra, metansulfonsyra och etandisulfonsyra. De kvaternara ammoniumsalterna utgoras exempelvis av klor-, brom- eller jodmetylater och -etylater, kloroch brombensylater och -allylater. The present invention relates to the preparation of new phenothiazine derivatives of the general formula: / \ S / \ II Iil — SO, N (CH 2), 1 1 A - Z and dcras salts with therapeutically useful acids and their quaternary ammonium derivatives. Among the therapeutically useful acids may be mentioned hydrochloric acid, phosphoric acid, nitric acid; sulfuric acid, maleic acid, fumaric acid, tartaric acid, oxalic acid, methanesulfonic acid and ethanedisulfonic acid. The quaternary ammonium salts are, for example, chlorine, bromine or iodine methylates and ethylates, chlorine and bromobenzylates and allylates.

I ovanstaende formel betecknar Z en monoeller dialkylaminoradikal, i vilken alkylradikalerna innehalla 1-5 kolatorner, exempelvis dimetylamino-, dietylamino-, dipropylamino-, metyletylamino- och etylpropylamino-radikaler, och A en radikal av ett tvavart, alifaLiskt kolvate med rak eller grenad kedj a innehallande 2-5 kolatomer, eventuellt substituerad med en radikal — B — Z', i vilken B betecknar en enkelbindning eller en metylenradikal och Z' liar samma betydelse som Z, samt fentiazinkarnans kvaveatom och Z-radikalens kvaveatom aro skilda frau varandra medelst minst tva kolatomer. In the above formula, Z represents a mono- or dialkylamino radical, in which the alkyl radicals contain 1-5 carbonators, for example dimethylamino, diethylamino, dipropylamino, methylethylamino and ethylpropylamino radicals, and A a radical of a double, aliphatic branched or straight-chain carbonate a containing 2-5 carbon atoms, optionally substituted with a radical - B - Z ', in which B represents a single bond or a methylene radical and Z' has the same meaning as Z, and the phent atom of the phentiazine nucleus and the nitrogen atom of the Z radical are separated by at least two carbon atoms.

Enligt uppfinningen kunna dessa fOreningar framstallas genom alkylering pa i och for sig kant satt av motsvarande primara eller sekundara aminer. According to the invention, these compounds can be prepared by alkylation per se set of corresponding primary or secondary amines.

Vissa av de fentiazinderivat, som framstallas enligt uppfinningen, exempelvis sadana, i vilka A betecknar en grenad kedja — CH2 — CH —, — CH2 — CH — CH, —, CH,CH, CII2 — CH„ — CH— CH(C1-12), -- etc. Some of the phenothiazine derivatives prepared according to the invention, for example those in which A represents a branched chain - CH 2 - CH -, - CH 2 - CH - CH 2 -, CH, CH, CII 2 - CH 2 - CH - CH (C 12), - etc.

CH,CH3 kunna foreligga i racemisk eller optiskt aktiv form. De optiskt aktiva derivaten kunna framstallas enligt vissa metoder, som beskrivas i det foljande, cm man utgar frail utgangsmaterial, som sjalva arc optiskt aktiva. De kunna aven framstallas ur motsvarande racemer med den gene-Fella formeln (I) genom optisk upplOsning. CH, CH3 may be in racemic or optically active form. The optically active derivatives can be prepared according to certain methods, which are described in the following, starting from free starting materials, which are themselves optically active. They can also be prepared from corresponding racemes of the gene-Fella formula (I) by optical resolution.

Dc enligt uppfinningen framstallda, nya derivaten ha v6rdefulla farmakodynamiska egenskaper och ha framfOr alit en stark inverkan pa det centrala nervsystemet, varfor de generellt kunna anvandas som nevroleptika, forstarkningsmedel for allmanbedOvningsmedel, exempelvis hexobarbital och eter, och for analgetika, exempelvis morfin, antiemetika och katatoniseringsmedel. Vissa av dem utgora aven spasmolytika, hypotensorer eller antihistaminer. The novel derivatives produced according to the invention have valuable pharmacodynamic properties and have a strong effect on the central nervous system, for which they can generally be used as neuroleptics, enhancers for general anesthetics, for example hexobarbital and ether, and for analgesics, for example morphine and antitonutics. . Some of them also contain antispasmodics, hypotensors or antihistamines.

Foljande, icke begransade exempel visa hur uppfinningen kan omsattas i praktiken. Smaltpunkterna ha bestamts pa Kofler-bank. The following non-limited examples show how the invention can be put into practice. The melting points have been determined at Kofler Bank.

Exempel. 3,3 g 3-dimetylsulfamido-10-(3'-aminopropy1)-fentiazin hist i 30 ml dioxan neutraliseras med 9,1 ml N saltsyra. Till denna losning satter man 22 ml 30-pro centig formalin och 0,2 g platinaoxid, varefter man omror kraftigt under vatgas med latt overtryck vid rurnstemperatur under 48 h. Sedan platinaoxiden har avlagsnats genom filtrering och losningsmedlet avlagsnats under reducerat tryck, tar man upp aterstoden med 50 ml N saltsyra. Man filtrerar bort det olosliga, staller filtratet basiskt med natriumkarbonat och extraherar med kloroform. Man torkar Over natriumsulfat och driver av kloroformen under vakuum. Man erhaller salunda 0,4 g 3 - dimetylsulfamido - l0-(3'- dimetylaminopropy1)- fentiazin, vars metansulfonat smalter vid 172° C. 2— — Example. 3.3 g of 3-dimethylsulfamido-10- (3'-aminopropyl) -phentiazine hist in 30 ml of dioxane are neutralized with 9.1 ml of N hydrochloric acid. To this solution is added 22 ml of 30% formalin and 0.2 g of platinum oxide, followed by stirring vigorously under water gas with slight overpressure at room temperature for 48 hours. After the platinum oxide has been removed by filtration and the solvent has been removed under reduced pressure, it is taken up the residue with 50 ml of N hydrochloric acid. The insoluble matter is filtered off, the filtrate is basified with sodium carbonate and extracted with chloroform. The sodium sulfate is dried and the chloroform is driven off under vacuum. 0.4 g of 3-dimethylsulfamido-10- (3'-dimethylaminopropyl) -phentiazine are thus obtained, the methanesulfonate of which melts at 172 DEG C.

Claims

1. A patent for the process: Process for the preparation of phentiazine compounds having a therapeutic effect, characterized in that in itself per se by alkylation of the corresponding primary or secondary amines there are prepared compounds of the general formula SF j-SO2N (CH3) 2 N Z in which formula Z represents a mono- or dialkylamino radical, in which the alkyl radical - or radicals contain 1-5 carbon atoms and A represents a double, aliphatic straight or branched chain aliphatic carbon radical containing 2-5 carbon atoms, which may be optionally substituted by a radical - B - Z ', in which B represents a single bond or a methylene radical and Z' has the same meaning as Z, the nitrogen atoms in the phentiazine nucleus and in Z are separated by at least two carbon atoms, and the base thus obtained is possibly transferred to the corresponding acid addition salt or a quaternary ammonium compound. Request publications: Patent documents from Sweden 166 674; France 1 060 189.