Novel crystalline forms of an antiviral benzimidazole compound
AssigneeSmithKline Beecham Corporation
InventorsBobby Neal Glover, Lian-Feng Huang, Robert William Lancaster, Stacey Todd Long, Michele Catherine Rizzolio, Eric Allen Schmitt, Barry Riddle Sickles
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Abstract
The invention relates to Form physical forms of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole, pharmaceutical compositions comprising the same, and their use in medical therapy.
Claims15
Form II 5,6,-dichloro-2-(isopropylamino)-1-β-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 Kα X-radiation.
A crystalline form of 5,6,-dichloro-2-(isopropylamino)-1-β-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 Kα 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.
5,6,-Dichloro-2-(isopropylamino)-1-β-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 Kα X-radiation.
Ethanol solvate of 5,6,-dichloro-2-(isopropylamino)-1-β-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 Kα 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.
Form V 5,6,-dichloro-2-(isopropylamino)-1-β-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 Kα X-radiation.
A crystalline form of 5,6,-dichloro-2-(isopropylamino)-1-β-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 Kα 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.
A composition comprising Form I 5,6,-dichloro-2-(isopropylamino)-1-β-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-β-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 Kα X-radiation.
A process for the production of 5,6,-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in an anhydrous crystalline form said process comprising the steps of:
- a) providing 5,6,-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in solution either in free base or salt form;
- b) isolating 5,6,-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole from the solution and optionally removing unbound solvent leaving the 5,6,-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in substantially dry form;
- c) treating 5,6,-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole with a solubilising solvent serving to convert an amount of said optionally dried 5,6,-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole into said 5,6,-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole anhydrous crystalline form;
- and
- d) isolating said anhydrous crystalline form.
Dependencies are inferred from the claim text.