BENZOFURAN,-PYRAN AND -DIOXAN-2-YLALKYLAMINOALKYL SUBSTITUTED GUANIDINE DERIVATIVES; PHARMACEUTICAL COMPOSITIONS; PREPARATORY METHODS AND INTERMEDIATES

摘要

PCT No. PCT/EP93/00435 Sec. 371 Date Jul. 29, 1994 Sec. 102(e) Date Jul. 29, 1994 PCT Filed Feb. 19, 1993 PCT Pub. No. WO93/17017 PCT Pub. Date Sep. 2, 1993The present invention is concerned with vasoconstricive [(benzodioxan, benzofuran or benzopyran)alkylamino]alkyl substituted guanidines having the formula IMAGE (I) the pharmaceutically acceptable acid addition salts thereof, and the stereochemically isomeric forms thereof, wherein X is O, CH2 or a direct bond; R1 is hydrogen or C1-6alkyl; R2 is hydrogen, C1-6alkyl, C3-6alkenyl or C3-6alkynyl; R3 is hydrogen or C1-6alkyl; or R2 and R3 may be taken together to form a bivalent radical of formula -(CH2)m-, wherein m is 4 or 5; or R1 and R2 taken together may form a bivalent radical of formula -CH=CH- or of formula -(CH2)n-, wherein n is 2, 3 or 4; or R3 may represent a bond when R1 and R2 taken together form a bivalent radical of formula -CH=CH-CH=, -CH=CH-N=, or -CH=N-CH=; R4 is hydrogen or C1-6alkyl;Alk1 is a bivalent C1-3alkanediyl radical; A is a bivalent radical of formula: IMAGE (a) IMAGE (b) IMAGE (c) IMAGE (d) IMAGE (e) wherein each R5 is hydrogen or C1-4alkyl; wherein each R6 is hydrogen or C1-4alkyl; Alk2 is C2-15alkanediyl or C5-7cycloalkanediyl; and each p is 0, 1 or 2; provided that [2-[(2,3-dihydro-1,4-benzodioxin-2-yl)methyl]amino]ethyl guanidine is excluded. Pharmaceuticals which are useful as vasoconstrictors. Compositions comprising said guanidine derivatives as active ingredients, processes for preparing said guanidine derivatives and novel N-cyano guanidine, intermediates; and a use as a medicine are described.