Patent GB-903200-A (GB)
Title: Bis-(halogenated-alkanoyl) diamines
IPC: C09B43/128
Filed: 1960-10-05
Abstract: The invention comprises bis(halogenated-alkanoyl)-diamines of general formula <FORM:0903200/IV (b)/1> wherein Y is CxH2x(CnH2n-2)CyH2y, or alkyen having its two free valance bonds on different carbon atoms and having from two to sixteen carbon atoms which may be interrupted by O, S, SO, SO2, NH, N(lower-alkyl), N(lower-alkenyl), N(lower - alkynyl), N[halogenated-(lower alkanoyl)], CH=CH or C=C, where x and y each are numbers from 0 to 6 inclusive and n is an integer from 3 to 8 inclusive, CxH2x and CyH2y representing lower-alkylan when x and y are each from 1 to 6 and CnH2n-2 representing cycloalkylene; Ac1 and Ac2 each are halogenated- (lower alkanoyl) having two or three halogen atoms; and Z1 and Z2 are H, hydrocarbon radicals of the formula R, hydroxyalkyl radicals of the formula-Y, -OH, hydrocarbonoxyalkyl radicals of the formula -Y,-O-R, acyloxyalkyl radicals of the formula -Y,-O-Ac1, cyanoalkyl radicals of the formula -Y,-CN or carbamylalkyl radicals of the formula -Y,-CONH2, where Y1 is alkylene having from two to six carbon atoms and having its two free valance bonds on different carbon atoms, R is a hydrocarbon radical having from one to eight carbon atoms and Ac1 is carboxylic-acyl having from one to eight carbon atoms, the compounds wherein both Z1 and Z2 are H being excluded when Y is hexamethylene and both Ac1 and Ac2 are dichlorocetyl or difluoroacetyl or when Y is ethylene and Ac1 and Ac2 are trifluoroacetyl, a process for preparing the above compounds which comprises preparing the compounds wherein Ac1 is the same as Ac2 by reacting a corresponding diamine having the formula Z1-NH-Y-NH-Z2 with at least two equivalents of an acylating agent providing the radical Ac1-or preparing the compounds wherein Ac1 is different from Ac2 by reacting a corresponding N-monoacylated diamine having the formula Z1(Ac1)N-Y-NHZ2 with an acylating agent providing the radical Ac2-, and, if a compound wherein Z1 and/or Z2 is -Y1-O-Ac1 is desired, reacting the corresponding compound wherein Z1 and/or Z2 is -Y1-OH with an appropriate acylating agent providing the radical Ac1-; also, in those cases in which Y is interrupted by an SO or SO2 group, a process comprising oxidation of the corresponding compound in which Y is interrupted by S or SO; and compositions comprising the above compounds plus a pharmaceutical carrier (see Group VI).  1,4-Bis-acetamidomethylcyclohexane is prepared by acetylation of 1,4-bis-aminomethylcyclohexane using acetyl chloride.  Compounds of general formula C2H5NH.CO.(CH2)n.CO. NHC2H5 are prepared by treatment of the corresponding acid chlorides Cl.CO.(CH2)n.CO. Cl with ethylamine. Also prepared in this way is <FORM:0903200/IV (b)/2> Diamines of general formula Z1NH.Y.NHZ2 are prepared by reduction of the above amides, using lithium aluminium hydride; by reaction of a dihalide Halogen-Y-Halogen with an amine; or by hydrogenation of a dicynanide CN-Y-CN.  N,N1 - bis - (2-Cyanoethyl)-1,4-diaminobutane is prepared by reaction of acrylonitrile with 1,4-diaminobutane.  The compounds claimed have amoebicidal, antispermogenic, and gonadal hormone potentiating properties.ALSO:Pharmaceutical compositions for oral or paranteral administration comprise a compound of general formula <FORM:0903200/VI/1> wherein Y is CxH2x(CnH2n-2)CyH2y or alkylene having its two free valence bonds on different carbon atoms and having 2-16 carbon atoms which may be interrupted by O, S, SO, SO2, NH, N(lower alkyl), N(lower alkenyl), N(lower alkynyl), N[halogenated - (lower alkanoyl)], CH = CH or C ­ C, where x and y each are numbers from 0 to 6 inclusive and n is an integer from 3 to 8 inclusive, CxH2x and CyH2y representing lower-alkylene when x and y are from 1 to 6 and CnH2n-2 representing cycloalkylene; Ac1 and Ac2 each are halogenated-(lower alkanoyl) having 2 or 3 halogen atoms; and Z1 and Z2 are H, hydrocarbon radicals of formula R, hydroxyalkyl radicals of formula -Y, -OH, hydrocarbonoxyalkyl radicals of the formula -Y1-O-R, acyloxyalkyl radicals of the formula -Y1-O-Ac1, cyanoalkyl radicals of the formula -Y1-CN or carbamylalkyl radicals of the formula -Y1-CONH2, where Y1 is alkylene having from 2-6 carbon atoms and having its two free valence bonds on different carbon atoms, R is a hydrocarbon radical having 1-8 carbon atoms and Ac1 is carboxylic-acyl having 1-8 carbon atoms, the compounds wherein both Z1 and Z2 are H being excluded when Y is hexamethylene and both Ac1 and Ac2 are dichloroacetyl or difluoroacetyl or when Y is ethylene and Ac1 and Ac2 are trifluoromethyl, plus a diluent or carrier, and may also include other active compounds, e.g. chloroquine, stilbestrol, and oxytetracycline.  The compositions have amoebicidal, antisparmogenic, and gonadal hormone potentiating action, and may be in the form of tablets, capsules, solutions or suspensions.