cycloalkyl - substituted glutaramidderivater, pharmaceutical preparations containing these compoundsrelations for medical use and their use in the manufacture of medicinal products for the treatment of hypertension, heart failure or renal insufficiency

摘要

Compounds of the formula: CHEM Wherein A completes a 5 or 6 membered carbocyclic ring which may be saturated or monounsaturated; R1 is H or (C1-C4)alkyl; R and R4 are H, (C1-C6)alkyl, C3-C7 cycloalkyl, benzyl, or an alternative biolabile ester-forming group; Y is either a direct bond or an alkylene group of from 1 to 6 carbon atoms; R2 is H, aryl, heterocyclyl, R6CONR5-, R7NR5CO-, R7NR5SO2- or R8SO2NR5-, with the proviso that Y is not a direct bond when R2 is H, aryl or heterocyclyl; wherein R5 is H, (C1-C6)alkyl or aryl(C1-C6)alkyl; R6 is (C1-C6)alkyl, aryl, aryl(C1-C6)alkyl, heterocyclyl, heterocyclyl(C1-C6)alkyl or a group of the formula R9R10R11C- wherein R9 is H, OH, (C1-C6)alkoxy, (C1-C6)alkyl, hydroxy(C1-C6)alkyl, aryl(C1-C6)alkyl, (C2-C6)alkenyl, heterocyclyl, heterocyclyl(C1-C6)alkyl, R12CONH-, R12SO2NH- or (R13)2N-; R10 and R11 are H or (C1-C6)alkyl; or R10 is H and R11 is amino(C1-C6)alkyl, imidazolylmethyl, aryl, aryl(C1-C6)alkyl, aryl(C1-C6)alkoxy(C1-C6)alkoxy, hydroxy(C1-C6)alkyl or methylthio(C1-C6)alkyl; or the two groups R10 and R11 form a 3 to 6 membered carbocyclic ring or a pyrrolidine or piperidine ring which may optionally be substituted by amino, (C2-C4)alkanoyl or aroyl; R12 is (C1-C6)alkyl, (C3-C7)cycloalkyl, aryl, aryl(C1-C6)alkyl, heterocyclyl or heterocyclyl(C1-C6)alkyl; each R13 is H, (C1-C6)alkyl, aryl(C1-C6)alkyl or the two groups R13 form a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C1-C4)alkyl-piperazinyl group; R7 is (C1-C6)alkyl, aryl, aryl(C1-C6)alkyl, heterocyclyl, heterocyclyl(C1-C6)alkyl or a group of the formula R10R11R14C- wherein R10 and R11 are as previously defined and R14 is (R13)2NCO-, R12OCH2- or R15OCO, wherein R12 and R13 are as previously defined and R15 is (C1-C6)alkyl, (C3-C7)cycloalkyl or aryl(C1-C6)alkyl; and R8 is (C1-C6)alkyl, aryl, aryl(C1-C6)alkyl, heterocyclyl or heterocyclyl(C1-C6)alkyl; R3 is a group of the formula: CHEM wherein R16 is H, halo, 4-OH, 4-(C1-C6 alkoxy), 4-(C3-C7 cycloalkoxy) 4-(C2-C6 alkenyloxy), 4-[(C1-C6 alkoxy)carbonyloxy], 4-[(C3-C7 cycloalkoxy)carbonyloxy], or 3-(C1-C4 alkyl)SO2NH-; and R20 is H, C1-C4 alkyl, C1-C4 alkoxy, C2-C6 alkanoyl or halo; or R3 is a group of the formula: CHEM wherein said groups may optionally be substituted in the fused benzene ring by C1-C4 alkyl, C1-C4 alkoxy, OH, halo or CF3; are antihypertensive agents of utility in the treatment of hypertension, heart failure and renal insufficiency.