P-thienylbenzylamides as agonists of angiotensin-(1-7) receptors, and methods of their preparation and use
View Patent ↗The invention relates to p-thienylbenzylamides of formula (I): in which R(1), R(2), R(3), R(4), R(5), R(6) and X have the meanings given in the description. The compounds of formula (I) are potent agonists of angiotensin-(1-7) receptors and are useful as pharmaceutically active compounds to treat and/or prevent hypertension; cardiac hypertrophy; cardiac insufficiency; coronary heart diseases, such as angina pectoris; and endothelial dysfunction or endothelial damage as a consequence, for example, of atherosclerotic processes or in association with diabetes mellitus.
1. A method for the treatment of endothelial dysfunction, which comprises administering to a patient in need thereof a pharmaceutically effective amount of one or more compounds of formula (I):
in which the indicated radicals have the following meanings:
R(1) is chosen from among
1. (C 1 -C 5 )-alkyl, unsubstituted or substituted by a radical chosen from among NH 2 , halogen, O—(C 1 -C 3 )-alkyl, CO—O—(C 1 -C 3 )-alkyl and CO 2 H;
2. (C 3 -C 8 )-cycloalkyl;
3. (C 1 -C 3 )-alkyl-(C 3 -C 8 )-cycloalkyl;
4. (C 6 -C 10 )-aryl, unsubstituted or substituted by a radical chosen from halogen and O—(C 1 -C 3 )-alkyl;
5. (C 1 -C 3 )-alkyl-(C 6 -C 10 )-aryl, where the aryl radical is unsubstituted or substituted by a radical chosen from halogen and O—(C 1 -C 3 )-alkyl;
6. (C 1 -C 5 )-heteroaryl; and
7. (C 1 -C 3 )-alkyl-(C 1 -C 5 )-heteroaryl;
R(2) is chosen from among
1. hydrogen;
2. (C 1 -C 6 )-alkyl, unsubstituted or substituted by a radical chosen from halogen and O—(C 1 -C 3 )-alkyl;
3. (C 3 -C 8 )-cycloalkyl;
4. (C 1 -C 3 )-alkyl-(C 3 -C 8 )-cycloalkyl;
5. (C 6 -C 10 )-aryl, unsubstituted or substituted by a radical chosen from among halogen, O—(C 1 -C 3 )-alkyl and CO—O—(C 1 -C 3 )-alkyl; and
6. (C 1-C 3 )-alkyl-(C 6 -C 10 )-aryl, unsubstituted or substituted by a radical chosen from halogen and O—(C 1 -C 3 )-alkyl;
R(3) is chosen from among
1. hydrogen;
2. COOH; and
3. COO—(C 1 -C 4 )-alkyl;
R(4) is chosen from among
1. hydrogen;
2. halogen; and
3. (C 1 -C 4 -alkyl;
R(5) is chosen from
1. hydrogen, and
2. (C 1 -C 6 )-alkyl;
R(6) is chosen from among
1. hydrogen;
2. (C 1 -C 6 )-alkyl;
3. (C 1 -C 3 )-alkyl-(C 3 -C 8 )-cycloalkyl; and
4. (C 2 -C 6 )-alkenyl;
X is chosen from
1. oxygen, and
2. NH;
in all the stereoisomeric forms thereof, and mixtures thereof in all ratios, and the physiologically tolerated salts thereof.