A process for the preparation of N- (β-guanidinoethyl) -6-azaspiro 2.5 octane, or acid addition salts or quaternary ammonium salts thereof.

摘要

Novel compounds of the Formula I wherein k represents an integer from 1 to 7, m represents 0 or an integer from 1 to 3 and n represents an integer from 1 to 4, the sum of k, m and n being at least 3 and at most 8, and A is a straight or branched C1- 6 alkylene radical, and acid addition salts and quaternary ammonium derivatives thereof, are prepared by reacting compounds of the Formula II with a compound of the formula Q-NH2, where Q represents a group of the formula R-S-C(: NH)-, R-O-C(: NH)- or NC- where R represents an alkyl group, or by reacting a compound of the Formula III with a compound of the formula Hal-A-NH-C(: NH)-NH2 or Hal-A1-CO-NH-C(: NH)-NH2, where Hal represents a halogen atom and A1 is such that -A1-CH2- is the same as A, and where appropriate converting a carbonyl group to a methylene group and if desired, converting a free base into an acid addition salt or quaternary ammonium derivative thereof. FORM:1058675/C2/1 FORM:1058675/C2/2 FORM:1058675/C2/3 N - (o - Aminoalkyl) - aza - spiroalkanes of the Formula II may be prepared by reacting an unsubstituted aza-spiroalkane with an o -haloalkyl nitrile and reducing the resulting N - (o - cyanoalkyl) - aza - spiroalkane. Unsubstituted aza - spiroalkanes may be obtained by reducing the corresponding cyclicimides.ALSO:Therapeutic compositions with hypotensive properties comprise compounds of the formula FORM:1058675/A5-A6/1 wherein k represent an integer from 1 to 7, m represents O or an integer from 1 to 3 and n represents an integer from 1 to 4, the sum of k, m and n being at least 3 and a most 8, and A represents a straight or branched C1-6 alkylene radical or acid addition salts or quaternary ammonium derivatives thereof in association with a pharmaceutically acceptable carrier, optionally in conjunction with a Reuwolfia alkaloid or a salidiuretic. Suitable Reuwolfia alkaloids include reserpine, rescinnamine, raupine, ajmaline and methyl yohimbate and the salidiuretic may be p-fluorophenyl-3-methyl-7- sulphamyl-6- chloro-3,4- dihydro-1,2, 4-benzthiadiazine 1,1-dioxide. The compositions may be administered orally in the forms of tablets, dragees and capsules or parenterally.