Alcanoic acid amides substituted by saturated O-heterocycles
View Patent ↗Compounds of the general formula (formula I) in which the meanings of the substituents R1 to R6 are as indicated in claim 1 , have renin-inhibiting properties and can be used as medicines.
1. A compound of the formula
or a salt thereof; in which
R 1 is 7-oxabicyclo[2.2.1]heptanyl-;
R 2 and R 3 are independently of one another hydrogen, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, or the two radicals together with the carbon atom to which they are bonded are C 3-8 cycloalkyl;
R 4 and R 5 are independently of one another hydrogen, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl or the two radicals together with the carbon atom to which they are bonded are C 3-8 cycloalkyl;
R 6 is a group —CH 2 —R 7 , —CH 2 —CO—R 7 , —CH 2 —CH 2 —R 7 , —CH 2 —NR 8 —CO—R 7 , —CH 2 —CO—NR 8 —CH 2 —R 7 , —CH 2 —CH 2 —NR 8 —R 7 , —CH 2 —CO—NR 8 —R 7 or —CO—NR 8 —CH 2 —R 7 ;
R 7 is optionally substituted phenyl, 2,3-dihydro-benzo[1,4]oxazinyl, 2,3-dihydro-benzo[1,4]thiazinyl or 1,2,3,4-tetrahydroquinolyl, wherein when R 7 is phenyl the optional substituents are selected from the group consisting of C 1-6 -alkyl, halogen, trifluoromethyl, C 1-4 -alkoxy-C 1-4 -alkyl, C 1-4 -alkoxy-C 1-4 -alkoxy-C 1-4 -alkyl, C 1-6 -alkoxy and C 1-4 -alkoxy-C 1-6 -alkoxy, and when R 7 is 2,3-dihydro-benzo[1,4]oxazinyl, 2,3-dihydro-benzo[1,4]thiazinyl or 1,2,3,4-tetrahydroquinolyl the optional substituents are selected from the group consisting of C 1-4 -alkoxycarbonylamino, C 1-4 -alkoxy-C 1-4 -alkoxy-C 1-4 -alkyl, C 1-4 -alkoxy-C 1-4 -alkyl, and N—C 1-4 -alkylcarbamoyl; and
R 8 is hydrogen, C 1-6 alkyl or C 1-6 alkanoyl.
2. A pharmaceutically useful salt of a compound according to claim 1 .
3. A compound according to claim 1 of formula (I′)
or a salt thereof; in which
R 1 , R 4 , R 5 and R 6 have the meaning as indicated for the compound of the formula (I) according to claim 1 .
4. A pharmaceutically useful salt of a compound according to claim 3 .
5. A pharmaceutical composition, comprising a compound of the formula (I) or a pharmaceutically useful salt thereof, according to claim 1 , and a pharmaceutically inert excipient.
6. A pharmaceutical combination in the form of a product or of a kit comprising individual components a) of a compound of the formula (I) or a pharmaceutically useful salt thereof, according to claim 1 , and b) of at least one pharmaceutical form whose active ingredient has a cardiovascular effect.
7. A compound according to claim 1 , in which the optional substituents for 2,3-dihydro-benzo[1,4]oxazinyl, 2,3-dihydro-benzo[1,4]thiazinyl and 1,2,3,4-tetrahydroquinolyl are selected from the group consisting of methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, methoxy-C 1-4 -alkoxy-C 1-4 -alkyl, ethoxy-C 1-4 -alkoxy-C 1-4 -alkyl, propoxy-C 1-4 -alkoxy-C 1-4 -alkyl, isopropoxy-C 1-4 -alkoxy-C 1-4 -alkyl, butoxy-C 1-4 -alkoxy-C 1-4 -alkyl, methoxy-C 1-4 -alkyl, ethoxy-C 1-4 -alkyl, propoxy-C 1-4 -alkyl, isopropoxy-C 1-4 -alkyl, butoxy-C 1-4 -alkyl, isobutoxy-C 1-4 -alkyl, sec-butoxy-C 1-4 -alkyl, tert-butoxy-C 1-4 -alkyl, N-methylcarbamoyl, N-ethylcarbamoyl, N-propylcarbamoyl and N-butylcarbamoyl.
8. A compound according to claim 7 , in which the C 1-4 -alkoxy is methoxy, ethoxy, propoxy or butoxy, and the C 1-4 -alkyl is methyl, ethyl, propyl or butyl.
9. A compound according to claim 1 , in which the C 1-4 -alkoxy-C 1-4 -alkoxy-C 1-4 -alkyl is methoxymethoxymethyl, 2-methoxyethoxymethyl or 3-methoxypropoxymethyl, and the C 1-4 -alkoxy-C 1-4 -alkyl is ethoxymethyl or 2-methoxyethyl.
10. A compound according to claim 1 having the formula:
or a pharmaceutically acceptable salt thereof.