Piperidinyl-terminated alkylamino ethynyl alanine amino diol compounds for treatment of hypertension

A pharmaceutical composition comprising a therapeutically-effective amount of a renin-inhibiting compound and a pharmaceutically-acceptable carrier or diluent, said renin-inhibiting compound selected from a family of compounds of Formula I:

• ##STR53## wherein A is selected from CO and SO.sub.2 ;
• wherein X is selected from oxygen atom and methylene;
• wherein R.sub.1 is selected from hydrido and alkyl;
• wherein B is a heterocyclic ring system of six to ten ring members with one ring member being a nitrogen atom that is a ring member of a six-membered ring, wherein said ring system may be monocyclic or bicyclic and may be fully saturated or partially saturated and may be fused to a benzene or cyclohexane ring, wherein the point of attachment of B to the backbone of the structure of Formula I may be through a bond to any substitutable position on said heterocyclic ring system of B and wherein any substitutable position of B may be optionally substituted with one or more radicals selected from alkyl, alkoxy, alkenyl, alkynyl, halo, trifluoromethyl, oxo, cyano and phenyl, and wherein the said heterocyclic ring nitrogen atom may be combined with oxygen to form an N-oxide;
• wherein R.sub.2 is selected from alkyl, cycloalkylalkyl, acylaminoalkyl, phenylalkyl and naphthylalkyl, and wherein the cyclic portion of any of said phenylalkyl, cycloalkylalkyl and naphthylalkyl groups may be substituted by one or more radicals selected from halo, hydroxy, alkoxy and alkyl;
• wherein each of R.sub.3 and R.sub.5 is independently selected from hydrido and alkyl;
• wherein R.sub.4 is selected from ##STR54## wherein V is selected from hydrido, alkyl, benzyl and phenyl;
• wherein each of R.sub.8 and R.sub.9 is a radical independently selected from hydrido, alkyl, alkenyl and phenyl;
• wherein R.sub.6 is selected from alkyl, cycloalkylalkyl and phenylalkyl, any one of which may be substituted with one or more groups selected from alkyl, hydroxy and alkoxy;
• wherein R.sub.7 is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl and alkenyl;
• wherein p is a number selected from zero through five, inclusive;
• wherein q is a number selected from zero through five, inclusive;
• and wherein n is a number selected from zero through five, inclusive;
• or a pharmaceutically-acceptable salt thereof.

A therapeutic method for treating a circulatory-related disorder, said method comprising administering to a subject susceptible to or afflicted with such disorder a therapeutically-effective amount of a compound of Formula I:

• ##STR63## wherein A is selected from CO and SO.sub.2 ;
• wherein X is selected from oxygen atom and methylene;
• wherein R.sub.1 is selected from hydrido and alkyl;
• wherein B is a heterocyclic ring system of six to ten ring members with one ring member being a nitrogen atom that is a ring member of a six-membered ring, wherein said ring system may be monocyclic or bicyclic and may be fully saturated or partially saturated and may be fused to a benzene or cyclohexane ring, wherein the point of attachment of B to the backbone of the structure of Formula I may be through a bond to any substitutable position on said heterocyclic ring system of B and wherein any substitutable position of B may be optionally substituted with one or more radicals selected from alkyl, alkoxy, alkenyl, alkynyl, halo, trifluoromethyl, oxo, cyano and phenyl, and wherein the said heterocyclic ring nitrogen atom may be combined with oxygen to form an N-oxide;
• wherein R.sub.2 is selected from alkyl, cycloalkylalkyl, acylaminoalkyl, phenylalkyl and naphthylalkyl, and wherein the cyclic portion of any of said phenylalkyl, cycloalkylalkyl and naphthylalkyl groups may be substituted by one or more radicals selected from halo, hydroxy, alkoxy and alkyl;
• wherein each of R.sub.3 and R.sub.5 is independently selected from hydrido and alkyl;
• wherein R.sub.4 is selected from ##STR64## wherein V is selected from hydrido, alkyl, benzyl and phenyl;
• wherein each of R.sub.8 and R.sub.9 is a radical independently selected from hydrido, alkyl, alkenyl and phenyl;
• wherein R.sub.6 is selected from alkyl, cycloalkylalkyl and phenylalkyl, any one of which may be substituted with one or more groups selected from alkyl, hydroxy and alkoxy;
• wherein R.sub.7 is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl and alkenyl;
• wherein p is a number selected from zero through five, inclusive;
• wherein q is a number selected from zero through five, inclusive;
• and wherein n is a number selected from zero through five, inclusive;
• or a pharmaceutically-acceptable salt thereof.