Non-peptidyl beta-aminoacyl aminodiol carbamates as anti-hypertensive agents

Claim 2

A compound of the formula: wherein X is selected from wherein Y and Q are selected from CH 2 , 0, S, SO, SO 2 and NR 11 , wherein R 10 is H or lower alkyl, R 11 is selected from H, phenyl and and wherein R 12 is H or lower alkyl; wherein each of m and n is independently an integer from 1 through 4; wherein each of r, t, u and v is independently an integer from zero through two; wherein p is an integer from 1 through 3; wherein each of a through d is independently an integer from zero through 3; wherein T is selected from one or more groups selected from H, linear or branched lower alkyl, alkoxy, oxo, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; wherein A is selected from O and S; wherein R 1 is selected from H, linear or branched lower alkyl, haloalkyl, alkylcycloalkyl, alkylcycloalkenyl and alkoxycarbonyl; wherein R 2 is selected from linear or branched lower alkyl, imidazolemethyl and benzyl; wherein R 3 is selected from lower alkyl, acylaminoalkyl, benzyl, naphthylmethyl, aryl and benzyl substituted at the phenyl portion by halo or lower alkyl or by both; wherein each of R 4 and R s is independently selected from H or lower alkyl; wherein R s is selected from H and phenyl; wherein R 7 is selected from substituted or unsubstituted cycloalkyl, phenyl, cycloalkylalkyl and phenylalkyl, any one of which may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; and wherein each of R 8 and R 9 is independently selected from the groups H, lower alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, benzyl, naphthyl and naphthylmethyl, any one of which groups having a substitutable position may be optionally substituted with or more of lower alkyi, aikoxy, alkenyl, alkynyl, halo, haloalkyl, cyano and phenyl, with the proviso that at least one of R 8 and R 9 is an aryl group.

Claim 3

Compound of Claim 1 of the formula: wherein A, X, R 1 through R 12 are as defined before. 3. Compound of Claim 2 wherein Y and Q are selected from 0, CH 2 , S, NR 11 wherein R 11 is H or wherein R 12 is H or lower alkyl; wherein each of m and r is an integer from 1 through 3 wherein each of r, t, u and v is independently an integer from zero through two; wherein p is one or two; wherein each of a through d is independently an integer from zero through 2; wherein T is selected from one or more groups selected from H, lower alkyl, alkoxy, oxo and halo; wherein A is selected from 0 and S; wherein R 1 is selected from H, lower alkyl, alkylcycloalkyl and alkoxycarbonyl; wherein R 2 is selected from lower alkyl, imidazolemethyl and benzyl; wherein R 3 is selected from lower alkyl, acylaminoalkyl, benzyl, napthylmethyl, aryl and benzyl substituted at the phenyl portion by halo or lower alkyl or by both; wherein R 4 is selected from H and lower alkyl; wherein R s is H and lower alkyl; wherein R 6 is selected from H and phenyl; wherein R 7 is selected from cyclohexylmethyl and benzyl; wherein each of R 8 and R 9 is independently selected from H, phenyl, naphthyl and phenyl substituted with one or more lower alkyl, alkoxy, alkenyl, halo, cyano and phenyl, with the proviso that at least one of R s and R 9 is phenyl.

Claim 4

Compound of Claim 3 wherein X is wherein Y is O, CH 2 , or S; m is 2; n is 2; T is one or more of H, lower alkyl and alkoxy; A is O or S; R, is H or lower alkyl; R 2 is lower alkyl; R 3 is benzyl; R 4 is H or methyl; R s is H or methyl; and R 6 is cyclohexylmethyl.

Claim 5

Compound of Claim 4 wherein Y is O; m is 2; n is 2; T is one or more of H or methyl; R 1 is selected from H, methyl, ethyl and isobutyl; R 2 is isobutyl; R 3 is selected from benzyl and napthylmethyl; R 4 is H or methyl; R s is H or methyl; R 6 is H and R 7 is cyclohexylmethyl.

Claim 6

Compound of Claim 5 which is O-(N-morpholinocarbonyl)-3-L-phenyllactyl-D,L-α-methyl-β-alaninamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane.

Claim 7

Compound of Claim 5 which is O-(N-morpholinocarbonyl)-3-L-phenyllactyl-D,L-α-methyl-β-alaninamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxypentane.

Claim 8

Compound of Claim 5 which is O-(N-morpholinocarbonyl)-3-L-phenyllactyl-D,L-α-methyl-β-alaninamide of (2S,3R)-2-amino-1-cyclohexyl-3,4-dihydroxybutane.

Claim 9

Compound of Claim 3 wherein X is wherein Y is selected from 0, CH 2 , S, SO and SO 2 ; each of r, t, u and v is independently zero or one; p is 1 or 2; T is one or more of H or lower alkyl; A is 0; R, is lower alkyl; R 2 is lower alkyl; R 3 is benzyl; R 4 . is H or methyl; R s is H or methyl; R 6 is H; and R 7 is cyclohexylmethyl.

Claim 10

Compound of Claim 9 wherein R, is isobutyl; R 2 is isobutyl; and R 7 is cyclohexylmethyl.

Claim 11

Compound of Claim 3 wherein x is wherein Q is O, CH 2 , or S; a is zero; b is 1; c is 1; d is zero; each T is independently one or more of H or lower alkyl; A is 0; R, is H or lower alkyl; R 2 is lower alkyl; R 3 is benzyl; R 4 is H or methyl; R s is H or methyl; R 6 is H; and R 7 is cyclohexylmethyl.

Claim 12

Compound of Claim 11 wherein Q is 0; R, is selected from H, methyl, ethyl and isobutyl; and R 2 is isobutyl.

Claim 13

Compound of Claim 12 wherein R, is isobutyl; and R 7 is cyclohexylmethyl.

Claim 14

Compound of Claim 11 wherein Q is S; R, is selected from H, methyl and isobutyl; and R 2 is isobutyl.

Claim 15

Compound of Claim 12 wherein R, is isobutyl; and R 7 is cyclohexylmethyl.

Claim 16

Compound of Claim 2 wherein X is wherein A is selected from O and S; wherein R 1 is selected from H, linear or branched lower alkyl, haloalkyl, alkylcycloalkyl, alkylcycloalkenyl and alkoxycarbonyl; wherein R 2 is selected from linear or branched lower alkyl, imidazolemethyl and benzyl; wherein R 3 is selected from lower alkyl, acylaminoalkyl, benzyl, naphthylmethyl, aryl and benzyl substituted at the phenyl portion by halo or lower alkyl or by both; wherein each of R4 and Rs is independently selected from H or lower alkyl; wherein R 6 is H or phenyl; wherein R 7 is selected from substituted or unsubstituted cycloalkyl, phenyl, cycloalkylalkyl and phenylalkyl, any one of which may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; wherein each of R 8 and Rg is independently selected from the groups H, lower alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, benzyl, naphthyl, and naphthylmethyl, any one of which groups having a substitutable position may be optionally substituted with or more of lower alkyl, alkoxy, halo, haloalkyl, cyano and phenyl, with the proviso that at least one of R 8 and R s is an aryl group.

Claim 17

Compound of Claim 16 wherein A is 0; R 1 is isobutyl; R 2 is isobutyl; R 3 is benzyl; R 4 is H or methyl; R s is H methyl; R 6 is H; R 7 is cyclohexylmethyl each of R s and Rg is independently selected from H, lower alkyl and phenyl, with at least one of R 8 and Rg being phenyl.

Claim 18

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: wherein X is selected from wherein Y and Q are selected from CH 2 , 0, S, SO, SO 2 and NR 11 , wherein R 10 is H or lower alkyl, R 11 is selected from H, phenyl and and wherein R 12 is H or lower alkyl; wherein each of m and n is independently an integer from 1 through 4; wherein each of r, t, u and v is independently an integer from one through two; wherein p is an integer from 1 through 3; wherein each of a through d is independently an integer from zero through 3; wherein T is selected from one or more groups selected from H, linear or branched lower alkyl, alkoxy, oxo, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; wherein A is selected from O and S; wherein R 1 is selected from H, linear or branched lower alkyl, haloalkyl, alkylcycloalkyl, alkylcycloalkenyl and alkoxycarbonyl; wherein R 2 is selected from linear or branched lower alkyl, imidazolemethyl and benzyl; wherein R 3 is selected from lower alkyl, acylaminoalkyl, benzyl, naphthylmethyl, aryl and benzyl substituted at the phenyl portion by halo or lower alkyl or by both; wherein each of R 4 and R s is independently selected from H or lower alkyl; wherein R s is H or phenyl; wherein R 7 is selected from substituted or unsubstituted cycloalkyl, phenyl, cycloalkylalkyl and phenylalkyl, any one of which may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; and wherein each of R s and Rs is independently selected from the groups H, lower alkyl, cycloalkyl, phenyl, benzyl, naphthyl and naphthylmethyl, any one of which groups having a substitutable position may be optionally substituted with or more of lower alkyl, alkoxy, alkenyl, alkynyl, halo, haloalkyl, cyano and phenyl, with the proviso that at least one of R 8 and Rs is an aryl group.

Claim 19

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: wherein X is selected from wherein Y and Q are selected from CH 2 , 0, S, SO, SO 2 and NR 11 , wherein R 10 is H or lower alkyl, R 11 is selected from H, phenyl and and wherein R 12 is H or lower alkyl; wherein each of m and n is independently an integer from 1 through 4; wherein each of r, t, u and v is independently an integer from one through two; wherein p is an integer from 1 through 3; wherein each of a through d is independently an integer from zero through 3; wherein T is selected from one or more groups selected from H, linear or branched lower alkyl, alkoxy, oxo, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; wherein A is selected from O and S; wherein R 1 is selected from H, linear or branched lower alkyl, haloalkyl, alkylcycloalkyl, alkylcycloalkenyl and alkoxycarbonyl; wherein R 2 is selected from linear or branched lower alkyl, imidazolemethyl and benzyl; wherein R 3 is selected from lower alkyl, acylaminoalkyl, benzyl, naphthylmethyl, aryl and benzyl substituted at the phenyl portion by halo or lower alkyl or by both; wherein each of R 4 and R s is independently selected from H or lower alkyl; wherein R s is H or phenyl; wherein R 7 is selected from substituted or unsubstituted cycloalkyl, phenyl, cycloalkylalkyl and phenylalkyl, any one of which may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; and wherein each of R s and Rs is independently selected from the groups H, lower alkyl, cycloalkyl, phenyl, benzyl, naphthyl and naphthylmethyl, any one of which groups having a substitutable position may be optionally substituted with or more of lower alkyl, alkoxy, alkenyl, alkynyl, halo, haloalkyl, cyano and phenyl, with the proviso that at least one of R 8 and Rs is an aryl group.

Claim 20

The composition of Claim 18 wherein said renin-inhibiting compound is of the formula wherein A, X and R 1 through R 12 are as defined before.

Claim 21

The composition of Claim 19 wherein Y and Q are selected from 0, CH 2 , S, NR,o wherein R 10 is H or wherein R " is H or lower alkyl; wherein each of m and n is independently an integer from 1 through 3; wherein each of r, t, u and v is independently an integer from zero through two; wherein p is one or two; wherein each of a through d is independently an integer from zero through 2; wherein T is selected from one or more groups selected from H, lower alkyl, alkoxy, oxo and halo; wherein A is selected from 0 and S; wherein R, is selected from H, lower alkyl, alkylcycloalkyl and alkoxycarbonyl; wherein R 2 is selected from lower alkyl, imidazolemethyl and benzyl; wherein R 3 is selected from lower alkyl, acylaminoalkyl, benzyl, napthylmethyl, aryl and benzyl substituted at the phenyl portion by halo or lower alkyl or by both; wherein R 4 is selected from H and lower alkyl; wherein R 5 is H or lower alkyl; Rs is H or phenyl; wherein R 7 is selected from cyclohexylmethyl and benzyl; wherein each of R 8 and R 9 is independently selected from H, phenyl, naphthyl and phenyl substituted with one or more lower alkyl, alkoxy, alkenyl, halo, cyano and phenyl, with the proviso that at least one of R 8 and R 9 is phenyl.

Claim 22

The composition of Claim 20 wherein X is wherein Y is O, CH 2 , or S; m is 2; n is 2; T is one or more of H or lower alkyl; A is 0 or S; R, is H or lower alkyl; R 2 is lower alkyl; R 3 is benzyl; R 4 is H or methyl; R s is H or methyl; R 6 is H; and R 7 is cyclohexylmethyl.

Claim 23

The Composition of Claim 21 wherein Y is 0; m is 2; r is 2; T is one or more of H or methyl; R, is selected from H, methyl, ethyl and isobutyl; R 2 is isobutyl; R 3 is selected from benzyl and napthylmethyl; R4 is H or methyl; R s is H or methyl; R 6 is H; and R 7 is cyclohexylmethyl.

Claim 24

The composition of Claim 22 which is O-(N-morpholinocarbonyl)-3-L-phenyllactyl-D,L-α-methyl-β-alaninamide leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane.

Claim 25

The composition of Claim 22 which is O-(N-morpholinocarbonyl)-3-L-phenyllactyl-D,L-α-methyl-β-alaninamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxypentane.

Claim 26

The composition of Claim 22 which is O-(N-morpholinocarbonyl)-3-L-phenyllactyl-D,L-α-methyl-β-alaninamide of (2S,3R)-2-amino-1-cyclohexyl-3,4-dihydroxybutane.

Claim 27

The composition of Claim 20 wherein X is wherein Y is selected from O, CH 2 , S, SO and SO 2 ; r, t, u and v is independently zero or one; p is 1 or 2; T is one or more of H or lower alkyl; A is 0; R, is lower alkyl; R 2 is lower alkyl; R 3 is benzyl; R 4 is H or methyl; R s is H or methyl; R 6 is H; and R 7 is cyclohexylmethyl.

Claim 28

The composition of Claim 26 wherein R, is isobutyl; R 2 is isobutyl; and R 7 is cyclohexylmethyl.

Claim 29

The composition of Claim 20 wherein X is wherein Q is 0, CH 2 , or S; a is zero; b is 1; c is 1; d is zero; each T is independently one or more of H or lower alkyl; A is O; R 1 is H or lower alkyl; R 2 is lower alkyl; R 3 is benzyl; R 4 is H or methyl; R 5 is H or methyl; Rs is H; and R 7 is cyclohexylmethyl.

Claim 30

The composition of Claim 28 wherein Q is 0; R 1 is selected from H, methyl, ethyl and isobutyl; and R 2 is isobutyl.

Claim 31

The composition of Claim 29 wherein R 1 is isobutyl; and R 7 is cyclohexylmethyl.

Claim 32

The composition of Claim 28 wherein Q is S; R 1 is selected from H, methyl and isobutyl; and R 2 is isobutyl.

Claim 33

The composition of Claim 31 wherein R 1 is isobutyl; and R 7 is cyclohexylmethyl.

Claim 34

The composition of Claim 20 wherein X is wherein A is selected from 0 and S; wherein R 1 is selected from H, linear or branched lower alkyl, haloalkyl, alkylcycloalkyl, alkylcycloalkenyl and alkoxycarbonyl; wherein R 2 is selected from linear or branched lower alkyl, imidazolemethyl and benzyl; wherein R 3 is selected from lower alkyl, acylaminoalkyl, benzyl, naphthylmethyl, aryl and benzyl substituted at the phenyl portion by halo or lower alkyl or by both; wherein each of R 4 and R 5 is independently selected from H or lower alkyl; wherein R s is H or phenyl; wherein R 7 is selected from substituted or unsubstituted cycloalkyl, phenyl, cycloalkylalkyl and phenylalkyl, any one of which may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; wherein each of R 8 and Rg is independently selected from the groups H, lower alkyl, cycloalkyl, phenyl, benzyl, naphthyl, and naphthylmethyl, any one of which groups having a substitutable position may be optionally substituted with or more of lower alkyl, alkoxy, alkenyl, alkynyl, halo, haloalkyl, cyano and phenyl, with the proviso that at least one of R 8 and R 9 is an aryl group.

Claim 35

The composition of Claim 33 wherein A is 0; R, is isobutyl; R 2 is isobutyl; R 3 is benzyl; R 4 is H or methyl; Rs is H or methyl; R 7 is cyclohexylmethyl each of R 8 and R s is independently selected from lower alkyl and phenyl, with at least one of R 8 and Rg being phenyl.

Claim 36

Use of a compound of the formula: wherein X is selected from wherein Y and Q are selected from CH 2 , 0, S, SO, S0 2 and NR 11 , wherein R 10 is H or lower alkvl, R 11 is selected from H, phenyl and and wherein R 12 isH or lower alkyl; wherein each of m and n is independently an integer from 1 through 4; wherein each of r, t, u and v is independently an integer from zero through two; wherein p is an integer from 1 through 3; wherein each of a through d is independently an integer from zero through 3; wherein T is selected from one or more groups selected from H, linear or branched lower alkyl, alkoxy, oxo, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; wherein A is selected from 0 and S: wherein R 1 is selected from H, linear or branched lower alkyl, haloalkyl, alkylcycloalkyl, alkylcycloalkenyl and alkoxycarbonyl; wherein R 2 is selected from linear or branched lower alkyl, imidazolemethyl and benzyl; wherein R 3 is selected from lower alkyl, acylaminoalkyl, benzyl, naphthylmethyl, aryl and benzyl substituted at the phenyl portion by halo or lower alkyl or by both; wherein each of R 4 and R s is independently selected from H or lower alkyl; wherein R 6 is H or phenyl; wherein R 7 is selected from substituted or unsubstituted cycloalkyl, phenyl, cycloalkylalkyl and phenylalkyl, any one of which may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; and wherein each of R 8 and R 9 is independently selected from the groups H, lower alkyl, cycloalkyl, phenyl, benzyl, naphthyl and naphthylmethyl, any one of which groups having a substitutable position may be optionally substituted with or more of lower alkyl, alkoxy, alkenyl, alkynyl, halo, haloalkyl, cyano and phenyl, with the proviso that at least one of R 8 and R s is an aryl group, for the manufacture of a medicament for treating hypertension.

Claim 37

Use of a compound of the formula: wherein X is selected from wherein Y and Q are selected from CH 2 , 0, S, SO, S0 2 and NR 11 , wherein R 10 is H or lower alkvl, R 11 is selected from H, phenyl and and wherein R 12 isH or lower alkyl; wherein each of m and n is independently an integer from 1 through 4; wherein each of r, t, u and v is independently an integer from zero through two; wherein p is an integer from 1 through 3; wherein each of a through d is independently an integer from zero through 3; wherein T is selected from one or more groups selected from H, linear or branched lower alkyl, alkoxy, oxo, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; wherein A is selected from 0 and S: wherein R 1 is selected from H, linear or branched lower alkyl, haloalkyl, alkylcycloalkyl, alkylcycloalkenyl and alkoxycarbonyl; wherein R 2 is selected from linear or branched lower alkyl, imidazolemethyl and benzyl; wherein R 3 is selected from lower alkyl, acylaminoalkyl, benzyl, naphthylmethyl, aryl and benzyl substituted at the phenyl portion by halo or lower alkyl or by both; wherein each of R 4 and R s is independently selected from H or lower alkyl; wherein R 6 is H or phenyl; wherein R 7 is selected from substituted or unsubstituted cycloalkyl, phenyl, cycloalkylalkyl and phenylalkyl, any one of which may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; and wherein each of R 8 and R 9 is independently selected from the groups H, lower alkyl, cycloalkyl, phenyl, benzyl, naphthyl and naphthylmethyl, any one of which groups having a substitutable position may be optionally substituted with or more of lower alkyl, alkoxy, alkenyl, alkynyl, halo, haloalkyl, cyano and phenyl, with the proviso that at least one of R 8 and R s is an aryl group, for the manufacture of a medicament for treating hypertension.

Claim 38

Use according to Claim 35 wherein said compound is of the formula wherein A, X and R 1 through R 12 are as defined before.

Claim 39

Use according to Claim 35 wherein Y and Q are selected from O, CH 2 , S, NR 11 wherein R 11 is H or wherein R 12 is H or lower alkyl; wherein each of m and n is independently an integer from 1 through 3; wherein each of r, t, u and v is independently an integer from zero through two; wherein p is one or two; wherein each of a through d is independently an integer from zero through 2; wherein T is selected from one or more groups selected from H, lower alkyl, alkoxy, oxo and halo; wherein A is selected from 0 and S; wherein R 1 is selected from H, lower alkyl, alkylcycloalkyl and alkoxycarbonyl; wherein R 2 is selected from lower alkyl, imidazolemethyl and benzyl; wherein R 3 is selected from lower alkyl, acylaminoalkyl, benzyl, napthylmethyl, aryl and benzyl substituted at the phenyl portion by halo or lower alkyl or by both; wherein R 4 is selected from H and lower alkyl; wherein R s is H or methyl; wherein R 6 is H or phenyl; wherein R 7 is selected from cyclohexylmethyl and benzyl; wherein each of Rs and R g is independently selected from H, phenyl, naphthyl and phenyl substituted with one or more lower alkyl, alkoxy, alkenyl, halo, cyano and phenyl, with the proviso that at least one of R s and Rg is phenyl.

Claim 40

Use according to Claim 37 wherein X is wherein Y is 0, CH 2 , or S; m is 2; n is 2; T is one or more of H, lower alkyl and alkoxy; A is 0 or S; R 1 is H or lower alkyl; R 2 is lower alkyl; R 3 is benzyl; R 4 is H or methyl; R s is H or methyl; R 6 is H; and R 7 is cyclohexylmethyl.

Claim 41

Use according to Claim 38 wherein Y is 0; m is 2; n is 2; T is one or more of H or methyl; R 1 is selected from H, methyl, ethyl and isobutyl; R 2 is isobutyl; R 3 is selected from benzyl and napthylmethyl; F 4 is H or methyl; R 5 is H or methyl; R s is H; and R 7 is cyclohexylmethyl.

Claim 42

Use according to Claim 39 wherein said compound is 0-(N-morpholinocarbonyl)-3-L-phenyllactyl-D,L-α-methyl-β-alaninamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane.

Claim 43

Use according to Claim 39 wherein said compound is 0-(N-morpholinocarbonyl)-3-L-phenyllactyl-D,L-α-methyl-β-alaninamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxypentane.

Claim 44

Use according to Claim 39 wherein said compound is 0-(N-morpholinocarbonyl)-3-L-phenyllactyl-D,L-α-methyl-β-alaninamide of (2S,3R)-2-amino-1-cyclohexyl-3,4-dihydroxybutane.

Claim 45

Use according to Claim 37 wherein X is wherein Y is selected from 0, CH 2 , S, SO and S0 2 ; each of r, t, u and v is independently zero or one; p is 1 or 2; T is one or more of H or lower alkyl; A is O; R 1 is lower alkyl; R 2 is lower alkyl; R 3 is benzyl; R 4 is H or methyl; R s is H or methyl; R 6 is H; and R 7 is cyclohexylmethyl.

Claim 46

Use according to Claim 43 wherein R 1 is isobutyl; R 2 is isobutyl; and R 7 is cyclohexylmethyl.

Claim 47

Use according to Claim 37 wherein X is wherein Q is 0, CH 2 , or S; a is zero; b is 1; c is 1; d is zero; each T is independently one or more of H or lower alkyl; A is 0; R, is H or lower alkyl; R 2 is lower alkyl; R 3 is benzyl; R 4 is H or methyl; R 5 is H or methyl; Rs is H; and R 7 is cyclohexylmethyl.

Claim 48

Use according to Claim 45 wherein Q is O; R, is selected from H, methyl, ethyl and isobutyl; and R 2 is isobutyl.

Claim 49

Use according to Claim 46 wherein R 1 is isobutyl; and R 7 is cyclohexylmethyl.

Claim 50

Use according to Claim 45 wherein Q is S; R, is selected from H, methyl and isobutyl; and R 2 is isobutyl.

Claim 51

Use according to Claim 48 wherein R, is isobutyl; and R 6 is cyclohexylmethyl.

Claim 52

Use according to Claim 37 wherein X is wherein A is selected from O and S; wherein R, is selected from H, linear or branched lower alkyl, haloalkyl, alkylcycloalkyl, alkylcycloalkenyl and alkoxycarbonyl; wherein R 2 is selected from linear or branched lower alkyl, imidazolemethyl and benzyl; wherein R 3 is selected from lower alkyl, acylaminoalkyl, benzyl, naphthylmethyl, aryl and benzyl substituted at the phenyl portion by halo or lower.alkyl or by both; wherein each of R 4 and R 5 is independently selected from H or lower alkyl; wherein R 6 is H or phenyl; wherein R 7 is selected from substituted or unsubstituted cycloalkyl, phenyl, cycloalkylalkyl and phenylalkyl, any one of which maY be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, lower alkenyl, lower alkynyl and cyano; wherein each of R 8 and R 9 is independently selected from the groups H, lower alkyl, cycloalkyl, phenyl, benzyl, naphthyl, and naphthylmethyl, any one of which groups having a substitutable position may be optionally substituted with or more of lower alkyl, alkoxy, alkenyl, alkynyl, halo, haloalkyl, cyano and phenyl, with the proviso that at least one of R 8 and R 9 is an aryl group.

Claim 53

Use according to Claim 50 wherein A is O; R 1 is isobutyl; R 2 is isobutyl; R 3 is benzyl; R 4 is H or methyl; R 5 is H or methyl; R s is H; R 7 is cyclohexylmethyl each of R s and Rg is independently selected from lower alkyl and phenyl, with at least one of R 8 and R 9 being phenyl.