Cycloalkyl-substituted glutaramide antihypertensive agents

A compound having the formula:

• ##STR388## and pharmaceutically acceptable salts thereof and bioprecursors therefor wherein:
• A completes a 5 or 6 membered carbocyclic ring which may be saturated or monounsaturated;
• R.sup.1 is H or (C.sub.1 -C.sub.4)alkyl;
• R and R.sup.4 are each independently H, (C.sub.1 -C.sub.6)alkyl (C.sub.3 -C.sub.7)cycloalyl, 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 which may be straight or branched chain;
• R.sup.2 is H, aryl, heterocyclyl, R.sup.6 CONR.sup.5 --, R.sup.7 NR.sup.5 CO--, R.sup.7 NR.sup.5 SO.sub.2 -- or R.sup.8 SO.sub.2 NR.sup.5 --, with the proviso that Y is not a direct bond when R.sup.2 is H, aryl or heterocyclyl;
• wherein R.sup.5 is H, (C.sub.1 -C.sub.6)alkyl or aryl (C.sub.1 -C.sub.6 (alkyl;
• R.sup.6 aryl, heterocyclyl, or a group of the formula:
• ##STR389## wherein R.sup.9 is H, OH, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6) alkyl, hydroxy(C.sub.1 -C.sub.6)alkyl, hydroxy (C.sub.1 -C.sub.6)alkyl, aryl, aryl(C.sub.2 -C.sub.6) heterocyclyl, heterocyclyl (C.sub.1 -C.sub.6)alkyl, R.sup.12 CONH--, R.sup.12 SO.sub.2 NH-- or (R.sup.13).sub.2 N--;
• R.sup.10 and R.sup.11 are each independently H or )alkyl;
• or R.sup.10 is H and R.sup.11 is amino )(C.sub.1 -C.sub.6)alkyl, imidazolylmethyl, aryl, aryl(C.sub.1 -C.sub.6)alkyl, hydroxy C.sub.1 -C.sub.6) or methylthio )alkyl;
• or the two groups R.sub.10 and R.sup.11 are joined together to form, with the carbon atom to which they are attached, a 3 to 6 membered carbocyclic ring or a ring which may optionally be substituted by amino, (C.sub.2 -C.sub.4) alkanoyl or aroyl;
• or a pyrrolidine or piperidien ring which is substiuted by amino, (C.sub.2 -C.sub.4) alkanoyl or aroyl;
• amino,
• R.sup.12 is (C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.7)cycloalkyl, aryl, aryl (C.sub.1 -C.sub.6)alkyl, heterocyclyl or heterocyclyl(C.sub.1 -C.sub.6)alkyl;
• R.sup.13 is H, (C.sub.1 -C.sub.6)alkyl, aryl or the two groups R.sup.13 are taken together to form, with the nitrogen to which they are attached, a pyrrolidinyl, piperidino, morpholino, piperazinyl or N--(C.sub.1 -C.sub.4 )alkyl-piperazinyl group;
• R.sup.7 is (C.sub.1 -c.sub.6)alkyl, aryl, aryl(C.sub.1 -C.sub.6)alkyl, heterocyclyl, heterocyclyl(C.sub.1 -C.sub.6)alkyl or a group of the formula:
• ##STR390## wherein R.sup.10 and R.sup.11 are as previously defined and R.sup.14 is (R.sup.13).sub.2 NCO--, R.sup.12 OCH.sub.2 or R.sup.15 OCO, wherein R.sup.12 an dR.sup.13 are as previously defined and R.sup.15 is (C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.7)cycloalkyl or aryl(C.sub.1 -C.sub.6)alkyl;
• and
• R.sup.8 is )alkyl, aryl, aryl(C.sub.1 -C.sub.6)alkyl, heterocyclyl or heterocyclyl(C.sub.1 -C.sub.6)alkyl;
• R.sup.3 is a group of the formula:
• ##STR391## wherein R.sup.16 is H, halo 4--OH, 4-(C.sub.1 C.sub.6 alkoxy), 4-(C.sub.3 --C.sub.7)cycloalkoxy),4-alkenyloxy), 4-[(C.sub.1 -C.sub.6 alkoxy)carbonyloxy], 4-[(C.sub.3 -C.sub.7 cycloalkoxy)carbonyloxy], or 3-(C.sub.1 -C.sub.4 alkyl)SO.sub.2 NH--;
• and is H alkoxy, (C.sub.2 -C.sub.6)alkanoyl or halo;
• or R.sup.3 is a group of the formula:
• ##STR392## wherein said groups may optionally be substituted in the fused benzene ring by (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4) alkoxy, OH, halo or CF.sub.3.