Dodecylsulfate Salt Of A Dipeptidyl Peptidase-Iv Inhibitor
The dodecylsulfate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]- 1 -(2,4,5-trifluorophenyl)butan-2-amine is a potent inhibitor of dipeptidyl peptidase-IV and is useful for the treatment of Type 2 diabetes. The invention also relates to a crystalline anhydrate of the dodecylsulfate salt as well as a process for its preparation, pharmaceutical compositions containing this novel form and methods of use for the treatment of Type 2 diabetes, hyperglycemia, insulin resistance, and obesity.
1 . A dodecylsulfate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine of structural formula I:
2 . The salt of claim 2 characterized in being a crystalline anhydrate.
3 . The anhydrate of claim 2 characterized by characteristic absorption bands obtained from the X-ray powder diffraction pattern with 2-theta values of 7.09, 9.46, 10.6, 11.90, 14.11, 17.28, 21.17, 22.92, and 23.87 degrees.
4 . The anhydrate of claim 3 further characterized by the X-ray powder diffraction pattern of FIG. 1 .
5 . The anhydrate of claim 2 characterized by a solid-state carbon-13 CPMAS nuclear magnetic resonance spectrum showing signals at 14.0, 31.8, and 69.0 p.p.m.
6 . The anhydrate of claim 5 further characterized by a solid-state carbon-13 CPMAS nuclear magnetic resonance spectrum showing signals at 118.3, 150.5, and 170.2 p.p.m.
7 . The anhydrate of claim 6 further characterized by the solid-state carbon-13 CPMAS nuclear magnetic resonance spectrum of FIG. 2 .
8 . The anhydrate of claim 2 characterized by a solid-state fluorine-19 MAS nuclear magnetic resonance spectrum showing signals at −60.1, −118.7, and −141.3 p.p.m.
9 . The anhydrate of claim 8 further characterized by a solid-state fluorine-19 MAS nuclear magnetic resonance spectrum showing signals at −132.9, −93.0, and −20.3 p.p.m.
10 . The anhydrate of claim 9 further characterized by the solid-state fluorine-19 MAS nuclear magnetic resonance spectrum of FIG. 3 .
11 . The anhydrate of claim 2 characterized by the thermogravimetric analysis curve of FIG. 4 .
12 . The anhydrate of claim 2 characterized by the differential scanning calorimetric curve of FIG. 5 .
13 . A salt comprising the ions of monoprotonated (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine cation and dodecylsulfate anion.
14 . A pharmaceutical composition comprising a therapeutically effective amount of the salt according to claim 12 in association with one or more pharmaceutically acceptable carriers.
15 . (canceled)
16 . A method of treating Type 2 diabetes comprising administering to a patient in need of such treatment a therapeutically effective amount of the salt according to claim 1 .