Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions
The present invention relates to substituted quinazolines of formula (I): wherein X and Y are defined as in claim 1 , the tautomers, stereoisomers, mixtures and salts thereof, which have valuable pharmacological properties, particularly an inhibitory effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).
1. A pharmaceutical composition comprising a compound of formula (I)
wherein
X and Y are the same or different and are independently selected from the following:
and
each R is independently selected from R1 and R2, in which
R1 and R2 are the same or different and are independently selected from 3-amino-piperidin-1-yl, (2-amino-2-methyl-propyl)-methylamino and (2-amino-propyl)-methylamino;
or a tautomer, stereoisomer, mixture or salt thereof,
optionally together with one or more pharmaceutically acceptable excipients.
2. The pharmaceutical composition according to claim 1 , in which
R1 and R2 are the same or different and are independently selected from 3-(R)-amino-piperidin-1-yl, (2-amino-2-methyl-propyl)-methylamino and (2-(S)-amino-propyl)-methylamino;
or a tautomer, enantiomer, diastereomer, mixture or salt thereof.
3. The pharmaceutical composition according to claim 1 , in which X and Y are the same, or a tautomer, enantiomer, diastereomer, mixture or salt thereof.
4. The pharmaceutical composition according to claim 1 , wherein the compound of formula (I) of formula (IB)
in which R1 and R2 are the same and are selected from 3-(R)-amino-piperidin-1-yl, (2-amino-2-methyl-propyl)-methylamino and (2-(S)-amino-propyl)-methylamino;
or a tautomer, enantiomer, diastereomer, mixture or salt thereof.
5. A pharmaceutical composition comprising a compound of the formula (IA):
or a tautomer, enantiomer, diastereomer, mixture or salt thereof,
optionally together with one or more pharmaceutically acceptable excipients.
6. The pharmaceutical composition according to claim 1 , wherein the compound of formula (I) is in the form of a physiologically acceptable salt with an inorganic or organic acid or base.
7. The pharmaceutical composition according to claim 1 in the form of a tablet, coated tablet or capsule.
8. Process for preparing a pharmaceutical composition according to claim 1 , characterised in that the compound of formula (I) or a physiologically acceptable salt thereof with an inorganic or organic acid or base is incorporated in one or more pharmaceutically acceptable excipients.
9. A method of treating type II diabetes mellitus or obesity, the method comprising administering the pharmaceutical composition according to claim 1 , and optionally one or more other active substances, to a patient.
10. The method according to claim 9 , wherein the one or more other active substances is selected from metformin, metformin; sulphonylureas, nateglinide, repaglinide, thiazolidinediones (e.g. pioglitazone), PPAR-gamma agonists, alpha-glucosidase blockers, insulin or insulin analogues, and GLP-1 and GLP-1 analogues.
11. The pharmaceutical composition according to claim 1 , further comprising metformin or metformin hydrochloride, optionally together with one or more pharmaceutically acceptable excipients.
12. The pharmaceutical composition according to claim 1 , further comprising pioglitazone or pioglitazone hydrochloride, optionally together with one or more pharmaceutically acceptable excipients.
13. The pharmaceutical composition according to claim 5 in the form of a tablet, coated tablet or capsule.
14. The pharmaceutical composition according to claim 5 , further comprising metformin or metformin hydrochloride, optionally together with one or more pharmaceutically acceptable excipients.
15. The pharmaceutical composition according to claim 5 , further comprising pioglitazone or pioglitazone hydrochloride, optionally together with one or more pharmaceutically acceptable excipients.