Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts
Crystalline salts of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine, compositions thereof, methods for their preparation, and methods for their use are disclosed.
1. A method of treating a subject having a disease selected from the group consisting of Type I diabetes, Type II diabetes and metabolic syndrome, said method comprising administering to said subject in need of such treatment an effective amount of a crystalline salt of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine selected from the group consisting of:
besylate salt having an X-ray power diffraction pattern substantially as shown in FIG. 15 ,
camsylate salt having an X-ray power diffraction pattern substantially as shown in FIG. 16 ,
esylate salt having an X-ray power diffraction pattern substantially as shown in FIG. 17 ,
HBr salt having an X-ray power diffraction pattern substantially as shown in FIG. 18 ,
HCl salt having an X-ray power diffraction pattern substantially as shown in FIG. 22 ,
HCl salt having an X-ray power diffraction pattern having peaks at degrees 2-theta diffraction angles of about 8.8, 10.8, 16.1, 17.4, 20.4, 20.9, 21.5, 21.7, 26.6, and 28.1,
HCl salt having an X-ray power diffraction pattern having peaks at degrees 2-theta diffraction angles of about 7.8, 10.1, 12.5, 18.4, 19.0, 20.8, 23.0, and 23.5,
mesylate salt having an X-ray power diffraction pattern substantially as shown in FIG. 19 ,
sulfate salt having an X-ray power diffraction pattern substantially as shown in FIG. 20 , and
tosylate salt having an X-ray power diffraction pattern substantially as shown in FIG. 21 .
2. The method of claim 1 wherein the crystalline salt is hydrochloride salt having substantially the same XRPD pattern as shown in FIG. 22 .
3. The method of claim 1 wherein the crystalline salt is hydrochloride salt having a XRPD pattern comprising peaks at degrees 2-theta diffraction angles of about 8.8, 10.8, 16.1, 17.4, 20.4, 20.9, 21.5, 21.7, 26.6, and 28.1.
4. The method of claim 3 wherein the crystalline salt is hydrochloride salt having substantially the same XRPD pattern as shown in FIG. 1 .
5. The method of claim 3 wherein the crystalline salt is hydrochloride salt having a DSC thermogram comprising an endotherm onset at about 191° C.
6. The method of claim 3 wherein the crystalline salt is hydrochloride salt having a DSC thermogram substantially as shown in FIG. 2 .
7. The method of claim 3 wherein the crystalline salt is hydrochloride salt having a Raman spectrum substantially as shown FIG. 4 .
8. The method of claim 1 wherein the crystalline salt is hydrochloride salt having a XRPD pattern comprising peaks at degrees 2-theta diffraction angles of about 7.8, 10.1, 12.5, 18.4, 19.0, 20.8, 23.0, and 23.5.
9. The method of claim 8 wherein the crystalline salt is hydrochloride salt having substantially the same XRPD pattern as shown in FIG. 5 .
10. The method of claim 8 wherein the crystalline salt is hydrochloride salt having a DSC thermogram comprising an endotherm onset at about 150° C.
11. The method of claim 8 wherein the crystalline salt is hydrochloride salt having a DSC thermogram substantially as shown in FIG. 6 .
12. The method of claim 1 , wherein said disease is Type II diabetes.
13. A method for one or more of stimulating insulin production, stimulating glucose-dependent insulin secretion, lowering blood glucose, or lowering blood triglyceride levels, said method comprising administering to a subject in need thereof an effective amount of a crystalline salt of 5 ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine selected from the group consisting of:
besylate salt having an X-ray power diffraction pattern substantially as shown in FIG. 15 ,
camsylate salt having an X-ray power diffraction pattern substantially as shown in FIG. 16 ,
esylate salt having an X-ray power diffraction pattern substantially as shown in FIG. 17 ,
HBr salt having an X-ray power diffraction pattern substantially as shown in FIG. 18 ,
HCl salt having an X-ray power diffraction pattern substantially as shown in FIG. 22 ,
HCl salt having an X-ray power diffraction pattern having peaks at degrees 2-theta diffraction angles of about 8.8, 10.8, 16.1, 17.4, 20.4, 20.9, 21.5, 21.7, 26.6, and 28.1,
HCl salt having an X-ray power diffraction pattern having peaks at degrees 2-theta diffraction angles of about 7.8, 10.1, 12.5, 18.4, 19.0, 20.8, 23.0, and 23.5,
mesylate salt having an X-ray power diffraction pattern substantially as shown in FIG. 19 ,
sulfate salt having an X-ray power diffraction pattern substantially as shown in FIG. 20 , and
tosylate salt having an X-ray power diffraction pattern substantially as shown in FIG. 21 .
14. The method of claim 1 further comprising administering a therapeutically effective amount of a DPP IV inhibitor.
15. The method of claim 14 wherein the DPP IV inhibitor is selected from the group consisting of sitagliptin, vildagliptin, denagliptin, saxagliptin, and alogliptin.
16. The method of claim 15 wherein said DPP IV inhibitor is sitagliptin or vildagliptin.
17. The method of claim 13 wherein the crystalline salt is hydrochloride salt having a XRPD pattern comprising peaks at degrees 2-theta diffraction angles of about 8.8, 10.8, 16.1, 17.4, 20.4, 20.9, 21.5, 21.7, 26.6, and 28.1.
18. The method of claim 13 wherein the crystalline salt is hydrochloride salt having a XRPD pattern comprising peaks at degrees 2-theta diffraction angles of about 7.8, 10.1, 12.5, 18.4, 19.0, 20.8, 23.0, and 23.5.
19. The method of claim 13 further comprising administering a therapeutically effective amount of a DPP IV inhibitor.
20. The method of claim 19 wherein the DPP IV inhibitor is selected from the group consisting of sitagliptin, vildagliptin, denagliptin, saxagliptin, and alogliptin.