Patent GB-782431-A (GB)
Title: New phenthiazine derivatives and their preparation
Inventor: JACOB ROBERT MICHEL
IPC: A61K31/54
Filed: 1954-11-17
Abstract: The invention comprises compounds of the formula <FORM:0782431/IV (a)/1> wherein Y represents a hydrogen or halogen atom, Z represents a sulphur atom or an SO or SO2 group, A and B each represent a divalent straight or branched hydrocarbon chain containing 2 to 4 carbon atoms, X represents a halogen atom or another acid residue, and R1, R2, R3 and R4 are alike or different and each represents either an individual alkyl group containing not more than 4 carbon atoms or an alkylene group containing not more than 4 carbon atoms and forming a part of a heterocyclic ring containing the nitrogen atom to which it is attached whereby one of the following variants of the foregoing formula is obtained <FORM:0782431/IV (a)/2> is replaced by <FORM:0782431/IV (a)/3> where A1 is an hydrocarbon chain containing at least one carbon atom fewer than A and the dotted lines indicate chains of methylene groups; <FORM:0782431/IV (a)/4> is replaced by <FORM:0782431/IV (a)/5> where the dotted lines indicate chains of methylene groups; <FORM:0782431/IV (a)/6> or <FORM:0782431/IV (a)/7> are replaced by pyrrolidino, piperidino, or morpholino groups. Such compounds are obtained by reacting a phenthiazine derivative of the general formula <FORM:0782431/IV (a)/8> with an amine of the general formula <FORM:0782431/IV (a)/9> one of the symbols P and Q representing the atom or acid residue X and the other representing the group <FORM:0782431/IV (a)/100> In examples: (1) 10-(2-dimethylaminoethyle phenthiazine and dimethylaminochloroethan) are heated in anhydrous ethanol to form [2-(10-phenthiazinyl)ethyl] - 2 - dimethylaminoethyl)-dimethylammonium chloride.  In a generally similar manner there are prepared (2) [2-(3-chloro - 10 - phenthiazinyl)ethyl] - (2 - diethylaminoethyl)dimethylammonium chloride; (3) [2 - (10 - phenthiazinyl)ethyl] - 2 - piperidinoethyl)dimethylammonium chloride; (4) [1-(10-phenthiazinyl) - 2 - propyl] - (2 - diethylaminoethyl)dimethylammonium chloride; (5) 1:4-dimethyl - 1 - [2 - (10 - phenthiazinyl)ethyl]-1 - piperazinium toluene - p - sulphonate; (6) [2 - (10 - phenthiazinyl)ethyl] - (2 - diethylaminoethyl)diethylammonium chloride; (7) [3 - (3 - chloro - 10 - phenthiazinyl)propyl] - (2-diethylaminoethyl)dimethylammonium chloride; (8) [3 - (10 - phenthiazinyl)propyl] - (2-diethylaminoethyl)pyrrolidinium chloride; (9) [1 - (9 - oxy - 10 - phenthiazinyl) - 2 - propyl]-(2 - diethylaminoethyl) dimethylammonium chloride; (10) [1-(10-phenthiazinyl)-2-propyl] (2 - piperidinoethyl)diethylammonium chloride; (11) [1 - (9:9 - dioxy - 10 - phenthiazinyl) - 2-propyl] - (2 - diethylaminoethyl)dimethyl ammonium chloride; (12) [2-(9:9-dioxy-10-phenthiazinyl)ethyl] - (2 - diethylaminoethyl) dimethylammonium chloride; (13) [2-(3-chloro-9:9 - dioxy - 10 - phenthiazinyl)ethyl] - (2-diethylaminoethyl) dimethylammonium chloride; (14) [3-(3-chloro-9:9-dioxy-10-phenthiazinyl)propyl] - (2 - diethylaminoethyl)dimethylammonium chloride; (15) [3-(9:9 dioxy - 10 - phenthiazinyl) - 2 - methylpropyl]-(2 - diethylaminoethyl) dimethylammonium chloride; (16) 1-methyl-1-(2-diethylaminoethyl) - 3 - (10 - phenthiazinylmethyl) piperidinium chloride.  Specification 769,440 is referred to.ALSO:Phenthiazine derivatives of the formula <FORM:0782431/VI/1> where Y represents a hydrogen or halogen atom, Z represents a sulphur atom or an SO or SO2 group, A and B each represent a divalent straight or branched hydrocarbon chain containing 2 to 4 carbon atoms, X represent a halogen atom or another acid residue and R1, R2, R3, R4 are the alike or different and each represents either an individual alkyl group containing not more than 4 carbon atoms or an alkylene group containing not more than 4 carbon atoms and forming a part of a heterocyclic ring containing the nitrogen atom to which it is attached possess a synergistic effect with regard to ganghoplegic products, including the compounds of Specification 769,440. Mixtures specified are the [2-(10-phenthiazinyl) - ethyl] - (2 - diethylaminoethyl) - dimethylammonium salts or [2-(3-chloro - 10 - phenthiazinyl) - ethyl] - (2 - diethylaminoethyl) - dimethylammonium salts with 1 : 4 - dimethyl - 1 : 4 - di - [5 - (3 - chloro - 10-phenthiazinyl) - 3 : 3 - dimethyl - 3 - azanium-1-pentyl]-piperazinium salts.