Proline derivatives and related compounds

Claim 2

A compound of the formula ##STR37## wherein R is hydroxy, NH 2 or lower alkoxy; R 1 and R 4 each is hydrogen, lower alkyl, phenyl or phenyl-lower alkyl; R 2 is hydrogen, lower alkyl, phenyl, substituted phenyl wherein the phenyl substituent is halo, lower alkyl or lower alkoxy, phenyl-lower alkyl, diphenyl-lower alkyl, triphenyl-lower alkyl, lower alkylthiomethyl, phenyl-lower alkylthiomethyl, lower alkanoylaminomethyl, ##STR38## R 6 -S- or R 7 ; R 3 is hydrogen, hydroxy or lower alkyl; R 5 is lower alkyl, phenyl or phenyl-lower alkyl; R 6 is lower alkyl, phenyl, substituted phenyl, wherein the phenyl substituent is halo, lower alkyl or lower alkoxy, hydroxy-lower alkyl or amino(carboxy)lower alkyl; ##STR39## M is 0 or S; m is 2; n and p each is 0, 1 or 2; and basic salts thereof, said lower alkoxy, lower alkyl and lower alkanoyl groups having up to seven carbon atoms.

Claim 3

A compound as in claim 1 wherein R is hydroxy or lower alkoxy; R 1 is hydrogen or lower alkyl; R 2 is hydrogen, R 5 --CO, R 6 --S--, or R 7 ; R 3 and R 4 each is hydrogen; R 5 is lower alkyl or phenyl; R 6 is lower alkyl; R 7 is ##STR40## wherein R, R 1 and R 4 have the same meaning as above; n is 0, 1 or 2; and p is 0.

Claim 4

A compound as in claim 1 wherein R 3 and R 4 each is hydrogen.

Claim 5

A compound as in claim 1 wherein R 3 is hydrogen.

Claim 6

A compound of the formula ##STR41## wherein R is hydroxy or lower alkoxy; R 1 is hydrogen or lower alkyl; R 2 is hydrogen or lower alkanoyl; n is 0, 1 or 2; and physiologically acceptable salts thereof, said lower alkoxy, lower alkyl and lower alkanoyl groups having up to seven carbon atoms.

Claim 7

A compound of the formula ##STR41## wherein R is hydroxy or lower alkoxy; R 1 is hydrogen or lower alkyl; R 2 is hydrogen or lower alkanoyl; n is 0, 1 or 2; and physiologically acceptable salts thereof, said lower alkoxy, lower alkyl and lower alkanoyl groups having up to seven carbon atoms.

Claim 8

A compound as in claim 5 wherein R is hydroxy.

Claim 9

A compound as in claim 5 wherein n is 1.

Claim 10

A compound as in claim 5 wherein R 2 is hydrogen or lower alkanoyl.

Claim 11

A compound as in claim 5 wherein R 2 is hydrogen.

Claim 12

A compound as in claim 5 wherein R 2 is acetyl.

Claim 13

A compound as in claim 5 wherein R 1 is hydrogen or lower alkyl.

Claim 14

A compound as in claim 5 wherein R 1 is hydrogen or methyl.

Claim 15

A compound as in claim 5 wherein R is hydroxy and R 1 is hydrogen or methyl.

Claim 16

A compound as in claim 5 wherein R is hydroxy, R 1 is hydrogen or methyl, R 2 is hydrogen or acetyl and n is 0, 1 or 2.

Claim 17

A compound as in claim 5 wherein R is hydroxy, R 1 and R 2 each is hydrogen and n is 0.

Claim 18

A compound as in claim 5 wherein R is hydroxy, R 1 is hydrogen, R 2 is acetyl and n is 1.

Claim 19

A compound as in claim 5 wherein R is hydroxy, R 1 is methyl, R 2 is acetyl and n is 1.

Claim 20

A compound as in claim 5 wherein R is hydroxy, R 1 and R 2 each is hydrogen and n is 1.

Claim 21

A compound as in claim 5 wherein R is hydroxy, R 1 is methyl, R 2 is hydrogen and n is 1.

Claim 22

A compound as in claim 5 wherein R is hydroxy, R 1 is hydrogen, R 2 is benzoyl and n is 1.

Claim 23

The L-form of a compound of claim 5.

Claim 24

The compound of claim 19 in which the proline is in the L-form.

Claim 25

A compound as in claim 1 wherein R is hydroxy, R 1 is hydrogen, R 2 is lower alkylthio and n is 1.

Claim 26

A compound as in claim 1 wherein R 2 is ##STR42## each R is hydroxy; each R 1 is hydrogen or lower alkyl; and each n is 0 to 2.

Claim 27

A compound as in claim 24 wherein each R is hydroxy; each R 1 is hydrogen and each n is 1.

Claim 28

The compound according to claim 1 having the name 1-(3-mercapto-2-D-methylpropanoyl)-L-proline.

Claim 29

The compound according to claim 1 having the name 1,1'-[dithiobis(2-D-methyl-3-propanoyl)]-bis-L-proline.

Claim 30

The compound of claim 18 in which the proline is in the L-form.

Claim 31

The compound of claim 17 in which the proline is in the L-form.

Claim 32

A composition for reducing blood pressure comprising about 10 to 500 mg. of a compound of claim 1 and a pharmaceutically acceptable vehicle therefor.

Claim 33

A composition for reducing blood pressure comprising about 10 to 500 mg. of a compound of claim 19 and a pharmaceutically acceptable vehicle therefor.

Claim 34

A composition for reducing blood pressure comprising about 10 to 500 mg. of a compound of claim 18 and a pharmaceutically acceptable vehicle therefor.

Claim 35

A composition for reducing blood pressure comprising about 10 to 500 mg. of the compound of claim 26 and a pharmaceutically acceptable vehicle therefor.

Claim 36

A composition for reducing blood pressure comprising about 10 to 500 mg. of the compound of claim 27 and a pharmaceutically acceptable vehicle therefor.

Claim 37

A method for reducing blood pressure which comprises administering a composition comprising a compound having the formula in claim 1 or a physiologically acceptable salt thereof and a pharmaceutically acceptable vehicle therefor.

Claim 38

A method for reducing blood pressure which comprises administering a composition comprising a compound of claim 19 and a pharmaceutically acceptable vehicle therefor.

Claim 39

A method for reducing blood pressure which comprises administering a composition comprising a compound of claim 18 and a pharmaceutically acceptable vehicle therefor.

Claim 40

A method for reducing blood pressure which comprises administering a composition comprising the compound of claim 27 and a pharmaceutically acceptable vehicle therefor.

Claim 41

A compound of the formula ##STR43## wherein R is hydroxy or lower alkoxy; R 1 and R 4 each is hydrogen, lower alkyl, phenyl or phenyl-lower alkyl; R 2 is hydrogen, lower alkyl, phenyl, substituted phenyl wherein the phenyl substituent is halo, lower alkyl or lower alkoxy, phenyl-lower alkyl, diphenyl-lower alkyl, triphenyl-lower alkyl, lower alkylthiomethyl, phenyl-lower alkylthiomethyl, lower alkanoylamidomethyl, ##STR44## R 6 -S- or R 7 ; R 3 is hydrogen, hydroxy or lower alkyl; R 5 is lower alkyl, phenyl or phenyl-lower alkyl; R 6 is lower alkyl, phenyl, substituted phenyl, wherein the phenyl substituent is halo, lower alkyl or lower alkoxy, hydroxy-lower alkyl or amino(carboxy)lower alkyl; ##STR45## M is 0 or S; m is 2; n and p each is 0, 1 or 2; and physiologically acceptable salts thereof, said lower alkoxy, lower alkyl and lower alkanoyl groups having up to seven carbon atoms.

Claim 42

A compound of the formula ##STR43## wherein R is hydroxy or lower alkoxy; R 1 and R 4 each is hydrogen, lower alkyl, phenyl or phenyl-lower alkyl; R 2 is hydrogen, lower alkyl, phenyl, substituted phenyl wherein the phenyl substituent is halo, lower alkyl or lower alkoxy, phenyl-lower alkyl, diphenyl-lower alkyl, triphenyl-lower alkyl, lower alkylthiomethyl, phenyl-lower alkylthiomethyl, lower alkanoylamidomethyl, ##STR44## R 6 -S- or R 7 ; R 3 is hydrogen, hydroxy or lower alkyl; R 5 is lower alkyl, phenyl or phenyl-lower alkyl; R 6 is lower alkyl, phenyl, substituted phenyl, wherein the phenyl substituent is halo, lower alkyl or lower alkoxy, hydroxy-lower alkyl or amino(carboxy)lower alkyl; ##STR45## M is 0 or S; m is 2; n and p each is 0, 1 or 2; and physiologically acceptable salts thereof, said lower alkoxy, lower alkyl and lower alkanoyl groups having up to seven carbon atoms.

Claim 43

A compound as in claim 39 wherein R 1 is hydrogen or lower alkyl; R 2 is hydrogen, R 5 --CO, R 6 --S--, or R 7 ; R 3 and R 4 each is hydrogen; R 5 is lower alkyl or phenyl; R 6 is lower alkyl; R 7 is ##STR46## wherein R is hydroxy or lower alkoxy; and R 1 and R 4 have the same meaning as above; and n is 0, 1 or 2.

Claim 44

A compound as in claim 39 wherein R 3 and R 4 each is hydrogen.

Claim 45

A method for reducing blood pressure which comprises administering a composition comprising the compound of claim 26 and a pharmaceutically acceptable vehicle therefor.