8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical composition

1. A compound of general formula I

wherein

R 1 is selected from the group consisting of: benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-(trifluoromethyl)-benzyl, 3-(trifluoromethyl)-benzyl, 4-(trifluoromethyl)-benzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2-(difluoromethoxy)-benzyl, 3-(difluoromethoxy)-benzyl, 4-(difluoromethoxy)-benzyl, 2-(trifluoromethoxy)-benzyl, 3-(trifluoromethoxy)-benzyl, 4-(trifluoromethoxy)-benzyl, a 2-cyanobenzyl, 3-cyanobenzyl, 4-cyanobenzyl, 2-cyano-3-methoxy-benzyl, 2-cyano-4-methoxy-benzyl, 2-cyano-5-methoxy-benzyl, 2-cyano-4-fluoro-benzyl, 2-cyano-5-fluoro-benzyl, 2-cyano-6-fluoro-benzyl, 2-(3-methoxy-phenyl)-2-oxo-ethyl, 2-(3 -methyl-2-oxo-2,3-dihydro-benzoxazol-4-yl)-2-oxo-ethyl, (pyridin-2-yl)methyl, (3-cyanopyridin-2-yl)methyl, (6-cyanopyridin-2-yl)methyl, (5-cyano-pyridin-2-yl)methyl, (4-cyano-pyridin-2-yl)methyl, (4-cyano-pyridin-3-yl)methyl, (3-cyano-pyridin-4-yl)methyl, (2-cyano-pyridin-3-yl)methyl, (2-cyano-pyridin-4-yl)methyl, (5-cyano-pyridin-3-yl)methyl, (6-cyano-pyridin-3-yl)methyl, (3-cyano-quinolin-2-yl)methyl, (1-cyano-isoquinolin-3-yl)methyl, (4-cyano-isoquinolin-1-yl)methyl, (4-methyl-quinazolin-2-yl)methyl, (quinoxalin-6-yl)methyl, (2,3-dimethyl-quinoxalin-6-yl)methyl, and ([1,5]naphthyridin-2-yl)methyl; and

R 2 is cyclopropyl or phenyl,

the tautomers and the salts thereof.

2. The compound of claim 1 , selected from the group consisting of:

1-[2-(3-Methyl-2-oxo-2,3-dihydro-benzoxazol-4-yl)-2-oxo-ethyl]-3-cyclopropyl-7-(2-butyn-1 -yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(4-methyl-quinazolin-2-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[2-(3-methoxy-phenyl)-2-oxo-ethyl]-3 -cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(4-cyano-isoquinolin-1-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(1-cyano-isoquinolin-3-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[([1,5]naphthyridin-2-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(2,3-dimethyl-quinoxalin-6-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(4-methyl-quinazolin-2-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[2-(3-methyl-2-oxo-2,3-dihydro-benzoxazol-4-yl)-2-oxo-ethyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[2-(3-methoxy-phenyl)-2-oxo-ethyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(4-cyano-isoquinolin-1-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(1-cyano-isoquinolin-3-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[([1,5]naphthyridin-2-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(2,3-dimethyl-quinoxalin-6-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(2-cyano-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(2-cyano-benzyl)-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(2-cyano-4-fluoro-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(2-cyano-5-fluoro-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(2-cyano-6-fluoro-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(3-cyanobenzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(4-cyanobenzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-benzyl-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(pyridin-2-yl)methyl]-3-phenyl-7-(2-butyn-l-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(2-chlorobenzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(2-fluoro-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(3-cyano-pyridin-2-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(6-cyano-pyridin-2-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(5-cyano-pyridin-2-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-1-[(4-cyano-pyridin-2-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(4-cyano-pyridin-3-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(3-cyano-pyridin-4-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(2-cyano-pyridin-3-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(2-cyano-pyridin-4-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(5-cyano-pyridin-3-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(6-cyano-pyridin-3-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(2-cyano-4-methoxy-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(2-cyano-5-methoxy-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[1(3-cyano-quinolin-2-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(2-methoxy-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(2-trifluoromethyl-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[(quinoxalin-6-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(3-fluoro-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(4-fluoro-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(3-chlorobenzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(4-chlorobenzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[3-(trifluoromethyl)-benzyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[4-(trifluoromethyl)-benzyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(3-methoxy-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-(4-methoxy-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[2-(difluoromethoxy)-benzyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[3-(difluoromethoxy)-benzyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine;

1-[4-(difluoromethoxy)-benzyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[2-(trifluoromethoxy)-benzyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[3-(trifluoromethoxy)-benzyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; 1-[4-(trifluoromethoxy)-benzyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine; and 1-(2-cyano-3-methoxy-benzyl)-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine.

3. The compound according to claim 1 , in the form of a physiologically acceptable salt with an inorganic or organic acid.

4. A pharmaceutical composition comprising a compound according to claim 1 , or a physiologically acceptable salt thereof, with one or more inert carriers or diluents.

5. A process for preparing the compound according to claim 1 , the process comprising:

(a) reacting a compound of general formula II

 wherein

R 1 and R 2 are defined as in claim 1 , and

Z 1 is a leaving group,

 with 3-aminopiperidine, the enantiomers, or the salts thereof;

or

(b) deprotecting a compound of general formula III

 wherein R 1 and R 2 are defined as in claim 1 .

6. A method for preventing type II diabetes mellitus or obesity, the method comprising the step of administering to a patient a pharmaceutically effective amount of the compound according to claim 1 .

7. The process of claim 5 , wherein Z 1 is a halogen atom, or a mercapto, methanesulphonyl or methanesulphonyloxy group.

8. The compound according to claim 1 , wherein R 2 is cyclopropyl.

9. The compound according to claim 1 , wherein R 2 is phenyl.