Lysine salts of 4-((phenoxyalkyl)thio)-phenoxyacetic acid derivatives
View Patent ↗The present invention is directed to a novel lysine salts, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by PPAR delta. The present invention is further directed to a novel process for the preparation of said lysine salts.
1. A method of treating a condition selected from the group consisting of phase I hyperlipidemia, pre-clinical hyperlipidemia, phase II hyperlipidemia, hypertension, coronary artery disease, coronary heart disease, hypertriglyceridemia, elevated serum levels of low-density lipoproteins (LDL), elevated serum levels of intermediate density lipoprotein (IDL), elevated serum levels of small-density LDL, elevated fasting plasma glucose (FPG)/HbA1c, elevated blood pressure, Type II diabetes, Metabolic Syndrome X, dyslipidemia, artherosclerosis and obesity, comprising administering to a subject in need thereof a therapeutically effective amount of a lysine salt of a compound of formula (Ia), wherein the salt is crystalline
2. The method of claim 1 , wherein the salt is a di-hydrate.
3. The method claim 1 , wherein the salt is a non-hydrate.
4. The method of claim 1 , wherein the lysine is L-lysine.
5. The method of claim 1 , wherein the compound of formula (Ia) is a crystalline, L-lysine salt of (R)-{4-[2-Ethoxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-acetic acid, comprising the following X-ray diffraction peaks:
Position
d-spacing
[°2θ]
[Å]
5.270
16.7702
7.882
11.2170
9.683
9.1342
10.370
8.5312
11.611
7.6218
19.561
4.5383
19.921
4.4571
20.652
4.3009
21.963
4.0471
23.162
3.8403
23.710
3.7527
23.883
3.7228
23.969
3.7188.
6. The method of claim 1 , wherein the compound of formula (Ia) is a crystalline, L-lysine salt of (R)-{4-[2-Ethoxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-acetic acid, comprising the following X-ray diffraction peaks:
Position
d-spacing
[°2θ]
[Å]
5.270
16.7702
9.683
9.1342
19.921
4.4571
23.162
3.8403.
7. The method of claim 1 , wherein the compound of formula (Ia) is a crystalline, L-lysine salt of (R)-{4-[2-Ethoxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-acetic acid, comprising the following X-ray diffraction peaks:
Position
d-spacing
[°2θ]
[Å]
5.285
16.7225
9.255
9.5558
9.501
9.3085
9.976
8.8665
15.017
5.8997
18.417
4.8176
18.799
4.7205
19.102
4.6462
19.430
4.5686
19.990
4.4418
20.327
4.3689
20.643
4.3028
21.276
4.1762
21.989
4.0423
22.693
3.9185
23.187
3.8361
23.931
3.7186
24.084
3.6953
25.642
3.4741
26.462
3.3683
27.973
3.1897.
8. The method of claim 1 , wherein the compound of formula (Ia) is a crystalline, L-lysine salt of (R)-{4-[2-Ethoxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-acetic acid, comprising the following X-ray diffraction peaks:
Position
d-spacing
[°2θ]
[Å]
9.255
9.5558
18.799
4.7205
19.102
4.6462
20.643
4.3028
21.989
4.0423
23.187
3.8361.