Crystalline forms of 3-[5-chloro-4-[(2,4-difluorobenzyl) oxy]-6-oxopyrimidin-1(6h)-yl]-n-(2-hydroxyethyl)-4-methylbenzamide
AssigneePharmacia & Upjohn Company
InventorJon G. SELBO
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Abstract
Crystalline forms of the p38 kinase inhibitor 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide is provided. Also provided are combinations and pharmaceutical compositions comprising the crystalline forms, and methods for the prophylaxis and/or treatment of a p38 kinase-mediated condition comprising administering to a subject a therapeutically effective amount of the crystalline forms.
Claims18
1-12. (canceled)
A method of treating or preventing an inflammatory condition, the method comprising administering to a subject having or susceptible to such condition or disorder a therapeutically or prophylactically effective amount of a pharmaceutical composition comprising 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide and one or more pharmaceutically acceptable excipients, wherein a detectable amount of the 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide is present as Form A crystalline 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide, wherein Form A has a melting point in a range from about 138.5° C. to about 142.5° C., and an X-ray powder diffraction pattern comprising peaks at 13.5±0.2, 21.1±0.2 and 27.2±0.2 degrees 2 theta.
A crystalline form of 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide having an X-ray powder diffraction pattern comprising a peak selected from the group consisting of 11.8±0.2, 13.7±0.2, 15.8±0.2, 21.4±0.2, 21.9±0.2, 26.2±0.2, and 26.9±0.2 degrees 2 theta.
A crystalline form of 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide having an X-ray powder diffraction pattern comprising a peak selected from the group consisting of 11.8±0.2, 13.7±0.2, 15.8±0.2, 21.4±0.2 and 26.9±0.2 degrees 2 theta.
A crystalline form of 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]N-(2-hydroxyethyl)-4-methylbenzamide having an X-ray powder diffraction pattern comprising a peak selected from the group consisting of 11.8±0.2, 15.8±0.2 and 26.9±0.2 degrees 2 theta.
A crystalline form of 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide of claim 1 having a dehydration point prior to 120° C.
A crystalline form of 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide having a dehydration point prior to 120° C., and an X-ray powder diffraction pattern comprising peaks at 11.8±0.2, 15.8±0.2 and 26.9±0.2 degrees 2 theta.
A crystalline form of 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide of having an X-ray powder diffraction pattern substantially as shown in FIG. 2.
A pharmaceutical composition comprising 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide and one or more pharmaceutically acceptable excipients, wherein a detectable amount of the 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide is present as Form B crystalline 3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide, wherein Form B has dehydration point prior to 120° C., and an X-ray powder diffraction pattern comprising peaks at 11.8±0.2, 15.8±0.2 and 26.9±0.2 degrees 2 theta.
Dependencies are inferred from the claim text.