Derivatives of mercaptoacyl prolines and pipecolic acids

A compound of the formula ##STR152## or a pharmaceutically acceptable salt thereof, wherein R is hydrogen or lower alkyl;

• R.sub.1 and R.sub.2 are independently selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, halo substituted lower alkyl, hydroxy substituted lower alkyl ##STR153## or R.sub.1 and R.sub.2 join together in a polymethylene chain of the formula ##STR154## X.sub.1, X.sub.2 and X.sub.3 are independently selected from the group consisting of oxygen and sulfur;
• R.sub.3 and R.sub.4 are independently selected from the group consisting of hydrogen, lower alkyl, lower alkylthio, --(CH.sub.2).sub.n --SH, and halo substituted lower alkyl;
• R.sub.6 is hydrogen or lower alkyl provided that R.sub.6 is lower alkyl only when R.sub.3 is lower alkyl;
• m is zero, one or two;
• n is one, two, or three;
• t is two or three;
• R.sub.7 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;
• R.sub.9 and R.sub.10 are both hydrogen, both lower alkyl, or one is hydrogen and the other is lower alkyl, halo substituted lower alkyl, hydroxy substituted lower alkyl, ##STR155## R.sub.5 is hydrogen, ##STR156## p-methoxybenzyloxycarbonyl, trityl, t-butoxycarbonyl, or provided that neither R.sub.3 nor R.sub.4 is --(CH.sub.2).sub.n --SH ##STR157## and R.sub.8 is lower alkyl, halo substituted lower alkyl, --(CH.sub.2).sub.r -cycloalkyl, ##STR158## wherein r is zero, one, two or three and R.sub.7 and X.sub.3 are as defined above.

A composition for treating hypertension containing a pharmaceutically acceptable carrier and from 10 to 500 mg. of a compound or mixture of compounds or pharmaceutically acceptable salts thereof of the formula ##STR164## wherein R is hydrogen or lower alkyl;

• R.sub.1 and R.sub.2 are independently selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, halo substituted lower alkyl, hydroxy substituted lower alkyl, ##STR165## or R.sub.1 and R.sub.2 join together in a polymethylene chain of the formula ##STR166## X.sub.1, X.sub.2 and X.sub.3 are independently selected from the group consisting of oxygen and sulfur;
• R.sub.3 and R.sub.4 are independently selected from the group consisting of hydrogen, lower alkyl, lower alkylthio, --(CH.sub.2).sub.n --SH, and halo substituted lower alkyl;
• R.sub.6 is hydrogen or lower alkyl provided that R.sub.6 is lower alkyl only when R.sub.3 is lower alkyl;
• m is zero, one, or two;
• n is one, two, or three;
• p and q are each one or two provided that both are not two;
• t is two or three;
• R.sub.7 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;
• R.sub.9 and R.sub.10 are both hydrogen, both lower alkyl, or one is hydrogen and the other is lower alkyl, halo substituted lower alkyl, hydroxy substituted lower alkyl, ##STR167## R.sub.5 is hydrogen, ##STR168## or provided that neither R.sub.3 nor R.sub.4 is --(CH.sub.2).sub.n --SH ##STR169## and R.sub.8 is lower alkyl, halo substituted lower alkyl, --(CH.sub.2).sub.r -cycloalkyl, ##STR170## wherein r is zero, one, two, or three and R.sub.7 and X.sub.3 are as defined above.

A composition for treating hypertension containing a pharmaceutically acceptable carrier, 15 to 300 mg. of a diuretic selected from the group consisting of chlorthiazide, hydrochlorothiazide, flumethiazide, hydroglumethiazide, benzdoflumethiazide, methchlothiazide, trichlormethiazide, polythiazide, benzthiazide, ethacrynic acid, tricrynafen, chlorthalidone, furosemide, musolimine, bumetanide, triamterene, amiloride, spironolactone and pharmaceutically acceptable salts thereof, and 30 to 600 mg. of a compound or mixture of compounds or pharmaceutically acceptable salts thereof of the formula ##STR171## wherein R is hydrogen or lower alkyl;

• R.sub.1 and R.sub.2 are independently selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, halo substituted lower alkyl, hydroxy substituted lower alkyl, ##STR172## or R.sub.1 and R.sub.2 join together in a polymethylene chain of the formula ##STR173## X.sub.1, X.sub.2 and X.sub.3 are independently selected from the group consisting of oxygen and sulfur;
• R.sub.3 and R.sub.4 are independently selected from the group consisting of hydrogen, lower alkyl, lower alkylthio, --(CH.sub.2).sub.n --SH, and halo substituted lower alkyl;
• R.sub.6 is hydrogen or lower alkyl provided that R.sub.6 is lower alkyl only when R.sub.3 is lower alkyl;
• m is zero, one or two;
• n is one, two, or three;
• p and q are each one or two provided that both are not two;
• t is two or three;
• R.sub.7 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;
• R.sub.9 and R.sub.10 are both hydrogen, both lower alkyl, or one is hydrogen and the other is lower alkyl, halo substituted lower alkyl, hydroxy substituted lower alkyl, ##STR174## R.sub.5 is hydrogen, ##STR175## or provided that neither R.sub.3 nor R.sub.4 is --(CH.sub.2).sub.n --SH ##STR176## and R.sub.8 is lower alkyl, halo substituted lower alkyl, ##STR177## wherein r is zero, one, two or three and R.sub.7 and X.sub.3 are as defined above.