17-iminomethylalkenyl-5 beta , 14 beta -androstane and 17-iminoalkyl-5 beta , 14 beta -androstane derivatives active on the cardiovascular system, and pharmaceutical compositions containing same

摘要

Disclosed are 17-iminomethylalkenyl and 17-iminoalkyl-14 beta -hydroxy-5 beta -androstane derivatives of the formula (I): <IMAGE> (I) wherein the symbol +Z means alpha or beta configuration or a Z or E configuration; A represents (CH2)m or -(CH=CH)n-; m represents an integer number from 1 to 6; n represents an integer number from 1 to 3; R2 represents hydrogen or hydroxy; R1 represents hydrogen, C2-C4 alkyl unsubstituted or substituted by NR4R5 wherein R4 and R5, which may be the same or different, represent hydrogen, C1-C4 alkyl or R4 and R5 may form, when taken together with the nitrogen atom, a five- or six- membered heterocyclic ring optionally containing one or more heteroatoms selected from oxygen and nitrogen; R3 represents NHC(=X)NR6R7 or OR8 wherein R6 and R7, which may be the same or different, represent hydrogen, methyl, or C2-C4 alkyl unsubstituted or substituted by NR4R5 wherein R4 and R5 have the previously defined meanings; R8 represents hydrogen, methyl, C2-C6 alkyl, unsubstituted or substituted by one or more NR4R5 or NHC(=NH)NH2, wherein R4 and R5 have the previously defined meanings; X represents O, S, or N+Z R9; R9 represents hydrogen, methyl, C2-C4 alkyl, C2-C4 acyl or phenyl, where the C2-C4 alkyl and C2-C4 acyl are unsubstituted or substituted by NR4R5, wherein R4 and R5 have the previously defined means; and R6, R7, and R9, taken two by two, may form, together with the heteroatoms to which they are linked, a five- , six- , or seven-membered heterocyclic ring; or mixtures of alpha and beta isomers at the 3-position; or mixtures of Z and E isomers of the group A-CH=N+Z R3; or pharmaceutically acceptable salts thereof. The compounds are useful for the treatment of cardiovascular disorders, such as heart failure and hypertension. Also, disclosed is a process for preparing the derivatives by reaction of the corresponding 17-alkyl or 17-methylalkenyl aldehyde with a compound of the formula H2NNHC(=X)NR6R7 or H2NOR8.