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Crystalline forms of an antiviral benzimidazole compound

Imported: 23 Feb '17 | Published: 22 Oct '02

Bobby Neal Glover, Lian-Feng Huang, Robert William Lancaster, Stacey Todd Long, Michele Catherine Rizzolio, Eric Allen Schmitt, Barry Riddle Sickles

USPTO - Utility Patents

Abstract

The invention relates to Form physical forms of 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole, pharmaceutical compositions comprising the same, and their use in medical therapy.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

FIG.

1. X-ray powder diffraction pattern of Form I of the compound of formula (I). This pattern was obtained in accordance with the procedures set forth in Example 18.

FIG.

2. X-ray powder diffraction pattern of Form II of the compound of formula (I). This pattern was obtained in accordance with the procedures set forth in Example 18.

FIG.

3. X-ray powder diffraction pattern of the ethanolate of the compound of formula (I). This pattern was obtained in accordance with the procedures set forth in Example 18.

FIG.

4. X-ray powder diffraction pattern of Form IV of the compound of formula (I). This pattern was obtained in accordance with the procedures set forth in Example 18.

FIG.

5. X-ray powder diffraction pattern of Form V of the compound of formula (I). This pattern was obtained in accordance with the procedures set forth in Example 18.

FIG.

6. X-ray powder diffraction pattern of Form VI of the compound of formula (I). This pattern was obtained in accordance with the procedures set forth in Example 18.

Claims

1. A crystalline form of Form II 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole having substantially the same X-ray powder diffraction pattern as FIG. 2, wherein said X-ray powder diffraction pattern is obtained with a diffractometer equipped with a diffracted beam curved graphite monochromator using copper K X-radiation.

2. A crystalline form of 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole characterized by an X-ray powder diffraction pattern expressed in terms of 2 theta angles and obtained with a diffractometer equipped with a diffracted beam curved graphite monochromator using copper K X-radiation, wherein said X-ray powder diffraction pattern comprises 2 theta angles at five or more positions selected from the group consisting of at five or more of the following positions: 7.91±0.09, 17.33±0.09, 18.23±0.95, 19.60±0.09, 21.88±0.09, 23.24±0.09, 23.92±0.09, 25.27±0.09, 27.70±0.09, and 29.21±0.09 degrees.

3. A crystalline form of 5,6-Dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole ethanol solvate having substantially the same X-ray powder diffraction pattern as FIG. 3, wherein said X-ray powder diffraction pattern is obtained with a diffractometer equipped with a diffracted beam curved graphite monochromator using copper K X-radiation.

4. A crystalline form of an ethanol solvate of 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole characterized by an X-ray powder diffraction pattern expressed in terms of 2 theta angles and obtained with a diffractometer equipped with a diffracted beam curved graphite monochromator using copper K X-radiation, wherein said X-ray powder diffraction pattern comprises 2 theta angles at five or more positions selected from the group consisting of at five or more of the following positions: 9.07±0.05, 10.38±0.05, 15.95±0.05, 17.72±0.05, 20.75±0.05, 21.37±0.05, 22.96±0.05, 23.93±0.05, 25.40±0.05, and 29.05±0.05 degrees.

5. A crystalline form of Form V 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole having substantially the same X-ray powder diffraction pattern as FIG. 5, wherein said X-ray powder diffraction pattern is obtained with a diffractometer equipped with a diffracted beam curved graphite monochromator using copper K X-radiation.

6. A crystalline form of 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole characterized by an X-ray powder diffraction pattern expressed in terms of 2 theta angles and obtained with a diffractometer equipped with a diffracted beam curved graphite monochromator using copper K X-radiation, wherein said X-ray powder diffraction pattern comprises 2 theta angles at five or more positions selected from the group consisting of at five or more of the following positions: 13.30±0.05, 18.13±0.05, 18.78±0.05, 20.41±0.05, 21.75±0.05, 23.02±0.05, 26.87±0.05, 28.34±0.05, 28.55±0.05, and 30.22±0.05 degrees.

7. A composition comprising an admixture of two or more forms or solvates of 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole selected from the group consisting of Form I, Form II, ethanol solvate, Form IV, Form V, and amorphous.

8. A composition comprising Form II 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole according to claim 1 and amorphous 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole.

9. A composition comprising Form I 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole having substantially the same X-ray powder diffraction pattern as FIG.

1 and Form V 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole having substantially the same X-ray powder diffraction pattern as FIG. 5, wherein said X-ray powder diffraction patterns are obtained with a diffractometer equipped with a diffracted beam curved graphite monochromator using copper K X-radiation.

10. The composition according to claim 9, further comprising Form IV 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole characterized by the X-ray powder diffraction pattern expressed in terms of 2 theta angles and obtained with a diffractometer equipped with a diffracted beam curved graphite monochromator using copper K X-radiation, wherein said X-ray powder diffraction pattern comprises 2 theta angles at five or more positions selected from the group consisting of at five or more of the following positions: 9.29±0.05, 16.04±0.05, 18.67±0.05, 22.06±0.05, 22.68±0.05, 23.34±0.05, 24.40±0.05, 29.64±0.05, 30.92±0.05, and 31.62±0.05 degrees.

11. A process for the production of 5,6-dichloro-2-(isopropylamino)-1--L-ribofuranosyl-1H-benzimidazole in an anhydrous crystalline form said process comprising the steps of: