Mercaptoacyl derivatives of keto substituted proline and pipecolic acid

Claim 2

A compound of the formula ##STR14## or a physiologically acceptable salt thereof, wherein R is hydrogen or lower alkyl; R 1 and R 3 are independently selected from the group consisting of hydrogen, lower alkyl, lower alkylthio, --(CH 2 ) n --SH, and halo substituted lower alkyl; R 2 is hydrogen or lower alkyl provided that R 2 is lower alkyl only when R 1 is lower alkyl; m is zero, one or two; n is one, two, or three; R 4 is hydrogen, ##STR15## p-methoxybenzyl, trityl, or provided that neither R 1 nor R 3 is --(CH 2 ) n --SH ##STR16## R 5 is lower alkyl, chloro, bromo or fluoro substituted lower alkyl, --(CH 2 ) r --cycloalkyl wherein the cycloalkyl group is a saturated ring of 3 to 7 carbons, ##STR17## r is zero, one, two, or three; R 6 is hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl or hydroxy; and X is oxygen or sulfur.

Claim 3

A compound of the formula ##STR18## or a physiologically acceptable salt thereof, wherein R 1 and R 2 are both lower alkyl of 1 to 4 carbons or R 2 is hydrogen and R 1 is hydrogen, lower alkyl of 1 to 4 carbons, trifluoromethyl, methylthio, or mercaptomethyl; m is zero or one; and R 4 is hydrogen, lower alkanoyl of 1 to 4 carbons, or benzoyl.

Claim 4

A compound of the formula ##STR18## or a physiologically acceptable salt thereof, wherein R 1 and R 2 are both lower alkyl of 1 to 4 carbons or R 2 is hydrogen and R 1 is hydrogen, lower alkyl of 1 to 4 carbons, trifluoromethyl, methylthio, or mercaptomethyl; m is zero or one; and R 4 is hydrogen, lower alkanoyl of 1 to 4 carbons, or benzoyl.

Claim 5

The compound of claim 2 wherein R 1 and R 2 are both methyl and m is one.

Claim 6

The compound of claim 2 wherein R 2 is hydrogen; R 1 is trifluoromethyl; and m is one.

Claim 7

The compound of claim 2 wherein R 2 is hydrogen; R 1 is methylthio; and m is one.

Claim 8

The compound of claim 2 wherein R 2 is hydrogen; R 1 is mercaptomethyl; and m is one.

Claim 9

The compound of claim 2 wherein R 1 and R 2 are both hydrogen.

Claim 10

The compound of claim 7 wherein m is one.

Claim 11

The compound of claim 8 wherein R 4 is acetyl.

Claim 12

The compound of claim 8 wherein R 4 is hydrogen.

Claim 13

The compound of claim 7 wherein m is zero.

Claim 14

The compound of claim 2 wherein R 2 is hydrogen, R 1 is methyl, and m is one.

Claim 15

The compound of claim 12 wherein R 4 is acetyl.

Claim 16

The compound of claim 12, wherein R 4 is hydrogen.

Claim 17

The compound of claim 14, (S)-1-(3-mercapto-2-methyl-1-oxopropyl)-4-oxo-L-proline.

Claim 18

A composition useful for treating hypertension comprising a pharmaceutically acceptable carrier and an effective amount of one or more hypotensive agents or physiologically acceptable salts thereof of the formula ##STR19## wherein R is hydrogen or lower alkyl; R 1 and R 3 are independently selected from the group consisting of hydrogen, lower alkyl, lower alkylthio, --(CH 2 ) n --SH, and halo substituted lower alkyl; R 2 is hydrogen or lower alkyl provided that R 2 is lower alkyl only when R 1 is lower alkyl; m is zero, one, or two; n is one, two, or three; R 4 is hydrogen, ##STR20## or provided that neither R 1 nor R 3 is --(CH 2 ) n --SH ##STR21## R 5 is lower alkyl, chloro, bromo, or fluoro substituted lower alkyl, --(CH 2 ) r --cycloalkyl wherein the cycloalkyl group is a saturated ring of 3 to 7 carbons, ##STR22## r is zero, one, two, or three; R 6 is hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl, or hydroxy; and X is oxygen or sulfur.

Claim 19

A composition useful for treating hypertension comprising a pharmaceutically acceptable carrier and an effective amount of one or more hypotensive agents or physiologically acceptable salts thereof of the formula ##STR19## wherein R is hydrogen or lower alkyl; R 1 and R 3 are independently selected from the group consisting of hydrogen, lower alkyl, lower alkylthio, --(CH 2 ) n --SH, and halo substituted lower alkyl; R 2 is hydrogen or lower alkyl provided that R 2 is lower alkyl only when R 1 is lower alkyl; m is zero, one, or two; n is one, two, or three; R 4 is hydrogen, ##STR20## or provided that neither R 1 nor R 3 is --(CH 2 ) n --SH ##STR21## R 5 is lower alkyl, chloro, bromo, or fluoro substituted lower alkyl, --(CH 2 ) r --cycloalkyl wherein the cycloalkyl group is a saturated ring of 3 to 7 carbons, ##STR22## r is zero, one, two, or three; R 6 is hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl, or hydroxy; and X is oxygen or sulfur.

Claim 20

The composition of claim 16 wherein the hypotensive agent is of the formula ##STR23## wherein R 1 and R 2 are both lower alkyl of 1 to 4 carbons or R 2 is hydrogen and R 1 is hydrogen, lower alkyl of 1 to 4 carbons, trifluoromethyl, methylthio, or mercaptomethyl; m is zero or one; and R 4 is hydrogen, lower alkanoyl of 1 to 4 carbons, or benzoyl.

Claim 21

The composition of claim 17 wherein R 1 , R 2 , and R 4 are hydrogen and m is one.

Claim 22

The composition of claim 17 wherein R 1 is methyl; R 2 and R 4 are hydrogen; and m is one.

Claim 23

The method of alleviating hypertension which comprises administering an effective amount of the composition of claim 16.