5-lipoxygenase-activating protein inhibitor
Described herein is the FLAP inhibitor 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxy-pyridin-3-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid, or a pharmaceutically acceptable salt thereof. Also described are methods of preparing the FLAP inhibitor, or a pharmaceutically acceptable salt thereof, including solvates, and polymorphs thereof. Also described herein are pharmaceutical compositions suitable for administration to a mammal that include the FLAP inhibitor, or a pharmaceutically acceptable salt thereof, and methods of using such pharmaceutical compositions for treating respiratory conditions or diseases, as well as other leukotriene-dependent or leukotriene mediated conditions or diseases.
1. A crystalline polymorphic Form C of sodium 3-[3-(tert-butylsulfanyl)-1-[4-(6-ethoxy-pyridin-3-yl)benzyl]-5-(5-methyl-pyridin-2-yl-methoxy)-1H-indol-2-yl]-2,2-dimethylpropionate:
having an X-ray powder diffraction spectrum with peaks comprising the 2-theta values listed below, obtained with a diffractometer using copper Kα-radiation;
Angle 2-Theta°
Intensity %
15.6
42.7
16.6
43.3
17.2
69
17.8
42.6
18.4
49.2
19.1
100
19.8
40.5
20.8
91.6
23.1
47.8
23.8
59.2.
2. The crystalline polymorphic Form C according to claim 1 having a single melting point at about 290° C. to about 295° C. as measured by differential scanning calorimetry (DSC).
3. The crystalline polymorphic Form C according to claim 1 having a differential scanning calorimetry (DSC) thermogram or a thermo-gravimetric analysis (TGA) thermogram substantially similar to the ones set forth in FIG. 15 .
4. The crystalline polymorphic Form C according to claim 1 having physical and chemical stability (at 5° C., 25° C./60% relative humidity (RH), and/or 40° C./75% RH for at least one month in a humidity chamber).
5. The crystalline polymorphic Form C according to claim 1 having an infrared (IR) spectrum substantially similar to the one set forth in FIG. 19 .
6. The crystalline polymorphic Form C according to claim 1 having an X-ray powder diffraction (XRPD) pattern substantially similar to an XRPD pattern obtained for crystals of Compound 2 obtained from methyl tert-butyl ether (MTBE) or acetonitrile.
7. The crystalline polymorphic Form C according to claim 1 , wherein the Crystalline Form C is desolvated.