GB1092767A - Improvements in or relating to chemotherapeutic amides of n-substituted aminomethyl-nor-camphane - Google Patents

Abstract

Novel compounds of Formula I <FORM:1092767/C2/1> where n is 0 or an integer from 1 to 5, R1 represents an alkyl, alkenyl, cycloalkyl, aralkyl or aryl group which may contain one or more halogen, alkoxy, alkylthio, amino or heterocyclic substituents, R2 represents an acyl radical derived from an acyclic, isocyclic or heterocyclic carboxylic acid, R3 represents a hydrogen atom or a hydroxyl, alkoxy, alkanoyloxy, isopropyl or dialkylamino group, or a morpholino, pyrrolidino, piperidino or piperazino group, including such a heterocyclic group substituted by one or more methyl, ethyl, isopropyl or hydroxy groups, and the 5,6-dehydro analogues thereof, are prepared by acylating the corresponding amine of Formula II <FORM:1092767/C2/2> or a 5,6-dehydro analogue thereof, wherein n is as defined above, R4 represents an alkyl, alkenyl, cycloalkyl, aralkyl or aryl group which may contain halogen, alkoxy, alkylthio, nitro or heterocyclic substituents, and R5 represents a hydrogen atom, or an hydroxyl, isopropyl or dialkylamino group, or a morpholino, pyrrolidino, piperidino or piperazino group, including such a heterocyclic group containing one or more methyl, ethyl, isopropyl or hydroxyl groups as substituents, with the appropriate acyl halide, and, when R4 represents a group containing a nitro substituent, reducing this to an amino group by catalytic hydrogenation of the product, and, if desired, alkylating or acylating the amide produced in which R5 represents an hydroxyl group to give the corresponding compound in which R5 represents an alkoxy or alkanoyloxy group. The amines of Formula II or the 5,6-dehydro analogues thereof may be prepared (1) by condensing the appropriate 2-aminomethyl-1,4-endomethylene - cyclohexane or - cyclohexene with a compound of formula R5(CH2)nX, where X is a halogen atom; (2) by reducing with lithium aluminium hydride a compound of Formula IV <FORM:1092767/C2/3> or the 5,6-dehydro analogue thereof, which compounds may be prepared by acylating 2-aminomethyl - 1,4 - endomethylene - cyclohexane or -cyclohexene with an acyl halide of formula R5(CH2)n- 1COX, where X is a halogen atom, R4 and R5 are as defined above, and n is an integer from 1 to 5; or (3) by catalytic hydrogenation of a compound of Formula V <FORM:1092767/C2/4> or the 5,6-dehydro analogue thereof, wherein n is an integer from 1 to 5, and R4 and R5 are as defined above, provided that R4 does not contain a nitro substituent, which compounds may be prepared by reacting 2-aminomethyl-1,4 - endomethylene - cyclohexane or - cyclohexene with an aldehyde of formula <FORM:1092767/C2/5> wherein R4 and R5 are as defined above n is an integer from 1-5. 2-(21-Hydroxyethyl)-aminomethyl - 3 - methyl - 1,4 - endomethylene-cyclohexane and cyclohexene are prepared by reacting 2 - aminomethyl - 3 - methyl - 1,4 -endomethylenecyclohexane or -cyclohexene with ethylene chlorhydrin. 2 - (N - Piperidino-ethyl) - aminomethyl - 3 - methyl - 1,4 - endomethylene-cyclohexane is prepared by reacting 2-aminomethyl - 3 - methyl - 1,4 - endomethylenecyclohexane with N - (b - chloroacetyl)-piperidine and reducing the 2 - (N - piperidinocarbonylmethyl) - aminomethyl - 3 - methyl 1,4-endomethylene-cyclohexane. Therapeutic compositions having neurotropic activity contain as active ingredient a compound of Formula I above, or a 5,6-dehyrdo analogue thereof.