Use of propargyl glycine amino propargyl diol compounds for treatment of renal failure

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:

• 146
• wherein A is selected from methylene, CO, SO and SO2;
• wherein x is selected from oxygen atom, methylene and
• 147
• with R10 selected from hydrido, alkyl and benzyl;
• wherein each of R1 and R9 is a group independently selected from hydrido, alkyl, cycloalkyl, alkoxyacyl, haloalkyl, alkoxycarbonyl, benzyloxycarbonyl, loweralkanoyl, haloalkylacyl, phenyl, benzyl, naphthyl, and naphthylmethyl, any one of which groups having a substitutable position may be optionally substituted with one or more radicals selected from alkyl, alkoxy, alkenyl, alkynyl, halo, haloalkyl, cyano and phenyl, and wherein the nitrogen atom to which R1 and R9 are attached may be combined with oxygen to form an N-oxide;
• wherein R2 is selected from hydrido, alkyl, dialkylaminoalkyl, alkylacylaminoalkyl, benzyl and cycloalkyl;
• wherein R3 is selected from alkyl, cycloalkylalkyl, acylaminoalkyl, phenylalkyl, naphthylmethyl, aryl, heterocyclicalkyl and heterocycliccycloalkyl, wherein the cyclic portion of any of said phenylalkyl, naphthylmethyl, aryl, heterocyclicalkyl and heterocycliccycloalkyl groups may be substituted by one or more radicals selected from halo, hydroxy, alkoxy and alkyl;
• wherein each of R4 and R6 is independently selected from hydrido, alkyl, benzyl and cycloalkyl;
• wherein each of R5 and R8 is independently selected from
• 148
• wherein V is selected from hydrido, alkyl, cycloalkyl, haloalkyl, benzyl and phenyl;
• wherein each of R13 and R14 is a radical independently selected from hydrido, alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, heterocyclic, heterocyclicalkyl and heterocycliccycloalkyl;
• wherein R7 is selected from substituted or unsubstituted alkyl, cycloalkyl, phenyl, cycloalkylalkyl and phenylalkyl, any one of which may be substituted with one or more groups selected from alkyl, hydroxy, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano;
• wherein each of R11 and R12 is independently selected from hydrido, alkyl, haloalkyl, dialkylamino and phenyl;
• and wherein m is zero or one;
• wherein n is a number selected from zero through five;
• wherein p is a number selected from zero through five;
• and wherein q is a number selected from zero through five;
• or a pharmaceutically-acceptable salt thereof.

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

• 166
• wherein A is selected from methylene, CO, SO and SO2;
• wherein X is selected from oxygen atom, methylene and
• 167
• with R10 selected from hydrido, alkyl and benzyl;
• wherein each of R1 and R9 is a group independently selected from hydrido, alkyl, cycloalkyl, alkoxyacyl, haloalkyl, alkoxycarbonyl, benzyloxycarbonyl, loweralkanoyl, haloalkylacyl, phenyl, benzyl, naphthyl, and naphthylmethyl, any one of which groups having a substitutable position may be optionally substituted with one or more radicals selected from alkyl, alkoxy, alkenyl, alkynyl, halo, haloalkyl, cyano and phenyl, and wherein the nitrogen atom to which R1 and R9 are attached may be combined with oxygen to form an N-oxide;
• wherein R2 is selected from hydrido, alkyl, dialkylaminoalkyl, alkylacylaminoalkyl, benzyl and cycloalkyl;
• wherein R3 is selected from alkyl, cycloalkylalkyl, acylaminoalkyl, phenylalkyl, naphthylmethyl, aryl, heterocyclicalkyl and heterocycliccycloalkyl, wherein the cyclic portion of any of said phenylalkyl, naphthylmethyl, aryl, heterocyclicalkyl and heterocycliccycloalkyl groups may be substituted by one or more radicals selected from halo, hydroxy, alkoxy and alkyl;
• wherein each of R4 and R6 is independently selected from hydrido, alkyl, benzyl and cycloalkyl;
• wherein each of R5 and R8 is independently selected from
• 168
• wherein V is selected from hydrido, alkyl, cycloalkyl, haloalkyl, benzyl and phenyl;
• wherein each of R13 and R14 is a radical independently selected from hydrido, alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, heterocyclic, heterocyclicalkyl and heterocycliccycloalkyl;
• wherein R7 is selected from substituted or unsubstituted alkyl, cycloalkyl, phenyl, cycloalkylalkyl and phenylalkyl, any one of which may be substituted with one or more groups selected from alkyl, hydroxy, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano;
• wherein each of R11 and R12 is independently selected from hydrido, alkyl, haloalkyl, dialkylamino and phenyl;
• and wherein m is zero or one;
• wherein n is a number selected from zero through five;
• wherein p is a number selected from zero through five;
• and wherein q is a number selected from zero through five;
• or a pharmaceutically-acceptable salt thereof.