Crystalline roxifiban
AssigneeDuPont Pharmaceuticals Company
InventorsMichael Blaise Maurin, Philip Ma, David John Meloni, Jaan A. Pesti, Lucius Thomas Rossano, Randall K. Ward, Jianguo Yin, Lin Hua Zhang, Goss S. Kauffman
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Abstract
The potent platelet glycoprotein IIb/IIIa antagonist, roxifiban, is produced in crystalline form. Crystalline roxifiban exists in two polymorphic forms, designated Form 1 and Form 2. These polymorphic forms are characterized by x-ray powder diffraction and solid-state carbon NMR. Pharmaceutical compositions and methods for the treatment or prevention of diseases mediated by platelet aggregation are described.
Claims30
The Form 1 polymorph of crystalline methyl-N3-[2-{3-(4-formamidinophenyl)-isoxazolin-5(R)-yl}-acetyl]-N2-(n-butyloxycarbonyl)-2,3-(S)-diaminopropionate acetate salt having a solid state 13C CP/MAS NMR spectrum substantially in accordance with that shown in FIG. 1.
The Form 1 polymorph of crystalline methyl-N3-[2-{3-(4-formamidinophenyl)-isoxazolin-5(R)-yl}-acetyl]-N2-(n-butyloxycarbonyl)-2,3-(S)-diaminopropionate acetate salt prepared by recrystallization of methyl-N3-[2-{3-(4-formamidinophenyl)-isoxazolin-5(R)-yl}-acetyl]-N2-(n-butyloxycarbonyl)-2,3-(S)-diaminopropionate acetate salt from a mixed solvent system.
The Form 2 polymorph of crystalline methyl-N3-[2-{3-(4-formamidinophenyl)-isoxazolin-5(R)-yl}-acetyl]-N2-(n-butyloxycarbonyl)-2,3-(S)-diaminopropionate acetate salt having a solid-state 13C CP/MAS NMR spectrum substantially in accordance with that shown in FIG. 2.
The Form 2 polymorph of crystalline methyl-N3-[2-{3-(4-formamidinophenyl)-isoxazolin-5(R)-yl}-acetyl]-N2-(n-butyloxycarbonyl)-2,3-(S)-diaminopropionate acetate salt prepared by recrystallization of methyl-N3-[2-{3-(4-formamidinophenyl)-isoxazolin-5(R)-yl}-acetyl]-N2-(n-butyloxycarbonyl)-2,3-(S)-diaminopropionate acetate salt from a mixed solvent system.
The Form 1 polymorph of crystalline methyl-N3-[2-{3-(4-formamidinophenyl)-isoxazolin-5(R)-yl}-acetyl]-N2-(n-butyloxycarbonyl)-2,3-(S)-diaminopropionate which has an x-ray powder diffraction pattern having four or more 2θ values selected from the group consisting of:
- 6.4±0.2, 9.6±0.2, 12.5±0.2, 14.7±0.2, 19.3±0.2, 21.5±0.2, 22.5±0.2, 23.2±0.2, 25.2±0.2, 27.5±0.2, and 32.2±0.2.
The Form 2 polymorph of crystalline methyl-N3-[2-{3-(4-formamidinophenyl)-isoxazolin-5(R)-yl}-acetyl]-N2-(n-butyloxycarbonyl)-2,3-(S)-diaminopropionate which has an x-ray powder diffraction pattern having four or more 2θ values selected from the group consisting of:
- 6.4±0.2, 9.6±0.2, 12.4±0.2, 13.6±0.2, 18.8±0.2, 20.7±0.2, 22.6±0.2, 23.1±0.2, 25.1±0.2, 26.1±0.2, 27.3±0.2, and 28.5±0.2.
Dependencies are inferred from the claim text.