Aralkyl-N-terminal cycloalkoxy-C terminal amino hydroxy β-amino acid derivatives

Claim 2

Compound of the formula ##STR29## wherein R 1 is selected from aralkyl groups represented by ##STR30## wherein each of Y and Z is independently selected from hydrido, lower alkyl, hydroxy, halo, alkoxy, carboxy, amino, alkylamino, dialkylamino, aryl, sulfhydryl and thioalkyl; wherein n is a number selected from zero through five, inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; wherein each of R 8 and R 9 is independently selected from hydrido and alkyl; and wherein any of the foregoing R 1 through R 9 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.

Claim 3

Compound of claim 1 wherein each of Y and Z is independently selected from hydrido, lower alkyl, hydroxy, halo, alkoxy, carboxy, amino, alkylamino, dialkylamino, aryl, sulfhydryl and thioalkyl; wherein n is a number selected from zero through five, inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from substituted or unsubstituted lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; wherein each of R 8 and R 9 is independently selected from hydrido and alkyl; and wherein any of the foregoing R 1 through R 9 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.

Claim 4

Compound of claim 2 wherein each of Y and Z is independently selected from hydrido, lower alkyl, hydroxy, halo, alkoxy, amino, alkylamino, dialkylamino, aryl, sulfhydryl and thioalkyl; wherein n is a number selected from zero through four, inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected from hydrido, methyl, ethyl, methoxymethyl and methylthiomethyl; wherein R 5 is selected from benzyl, cyclohexylmethyl, isobutyl and n-butyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; and wherein each of R 8 and R 9 is independently selected from hydrido and methyl; or a pharmaceutically-acceptable salt thereof.

Claim 5

Compound of claim 3 wherein each of Y and Z is independently selected from hydrido, chloro, fluoro, methoxy and dimethylamino; wherein n is a number selected from zero through four, inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected from methyl and ethyl; wherein R 5 is cycloexylmethyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; and wherein each of R 8 and R 9 is independently selected from hydrido and methyl; or a pharmaceutically acceptable salt thereof.

Claim 6

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 the formula ##STR31## wherein R 1 is selected from aralkyl groups represented by ##STR32## wherein each of Y and Z is independently selected from hydrido, lower alkyl, hydroxy, halo, alkoxy, carboxy, amino, alkylamino, dialkylamino, aryl, sulfhydryl and thioalkyl; wherein n is a number selected from zero through five. inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; wherein each of R 8 an R 9 is independently selected from hydrido and alkyl; and wherein any of the foregoing R 1 through R 9 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.

Claim 7

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 the formula ##STR31## wherein R 1 is selected from aralkyl groups represented by ##STR32## wherein each of Y and Z is independently selected from hydrido, lower alkyl, hydroxy, halo, alkoxy, carboxy, amino, alkylamino, dialkylamino, aryl, sulfhydryl and thioalkyl; wherein n is a number selected from zero through five. inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; wherein each of R 8 an R 9 is independently selected from hydrido and alkyl; and wherein any of the foregoing R 1 through R 9 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.

Claim 8

The composition of claim 5 wherein each of Y and Z is independently selected from hydrido, lower alkyl, hydroxy, halo, alkoxy, carboxy, amino, alkylamino, dialkylamino, aryl, sulfhydryl and thioalkyl; wherein n is a number selected from zero through five, inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from substituted or unsubstituted lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; wherein each of R 8 and R 9 is independently selected from hydrido and alkyl; and wherein any of the foregoing R 1 through R 9 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.

Claim 9

The composition of claim 6 wherein each of Y and Z is independently selected from hydrido, lower alkyl, hydroxy, halo, alkoxy, amino, alkylamino, dialkylamino, aryl, sulfhydryl and thioalkyl; wherein n is a number selected from zero through four, inclusive, wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected from hydrido, methyl, ethyl, methoxymethyl and methylthiomethyl; wherein R 5 is selected from benzyl, cyclohexylmethyl, isobutyl and n-butyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; and wherein each of R 8 and R 9 is independently selected from hydrido and methyl; or a pharmaceutically-acceptable salt thereof.

Claim 10

The composition of claim 7 wherein each of Y and Z is independently selected from hydrido, chloro, fluoro, methoxy and dimethylamino; wherein n is a number selected from zero through four, inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected form methyl and ethyl; wherein R 5 is cyclohexylmethyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; and wherein each of R 8 and R 9 is independently selected from hydrido and methyl; or a pharmaceutically-acceptable salt thereof.

Claim 11

A therapeutic method for treating hypertension, said method comprising administering to a hypertensive patient a therapeutically-effective amount of a compound of the formula ##STR33## wherein R 1 is selected from aralkyl groups represented by ##STR34## wherein each of Y and Z is independently selected from hydrido, lower alkyl, hydroxy, halo, alkoxy, carboxy, amino, alkylamino, dialkylamino, aryl, sulfhydryl and thioalkyl; wherein n is a number selected from zero through five, inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; wherein each of R 8 and R 9 is independently selected from hydrido and alkyl; and wherein any of the foregoing R 1 through R 9 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.

Claim 12

A therapeutic method for treating hypertension, said method comprising administering to a hypertensive patient a therapeutically-effective amount of a compound of the formula ##STR33## wherein R 1 is selected from aralkyl groups represented by ##STR34## wherein each of Y and Z is independently selected from hydrido, lower alkyl, hydroxy, halo, alkoxy, carboxy, amino, alkylamino, dialkylamino, aryl, sulfhydryl and thioalkyl; wherein n is a number selected from zero through five, inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; wherein each of R 8 and R 9 is independently selected from hydrido and alkyl; and wherein any of the foregoing R 1 through R 9 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.

Claim 13

The method of claim 9 wherein each of Y and Z is independently selected from hydrido, lower alkyl, hydroxy, halo, alkoxy, carboxy, amino, alkylamino, dialkylamino, aryl, sulfhydryl and thioalkyl; wherein n is a number selected from zero through five, inclusive; wherein each of R 2 and R 4 is independently selected form hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from substituted or unsubstituted lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; wherein each of R 8 and R 9 is independently selected from hydrido and alkyl; and wherein any of the foregoing R 1 through R 9 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.

Claim 14

The method of claim 10 wherein each of Y and Z is independently selected from hydrido, lower alkyl, hydroxy, halo, alkoxy, amino, alkylamino, dialkylamino, aryl, sulfhydryl and thioalkyl; wherein n is a number selected from zero through four, inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected from hydrido, methyl, ethyl, methoxymethyl and methylthiomethyl; wherein R 5 is selected from benzyl, cyclohexylmethyl, isobutyl and n-butyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; and wherein each of R 8 and R 9 is independently selected from hydrido and methyl; or a pharmaceutically-acceptable salt thereof.

Claim 15

The method of claim 11 wherein each of Y and Z is independently selected from hydrido, chloro, fluoro, methoxy and dimethylamino; wherein n is a number selected from zero through four, inclusive; wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected from methyl and ethyl; wherein R 5 is cyclohexylmethyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; and wherein each of R 8 and R 9 is independently selected from hydrido and methyl; or a pharmaceutically-acceptable salt thereof.