Patent EA-002970-B1 (EA)
Title: Novel crystalline forms of an antiviral benzimidazole compound, method for obtaining same, use thereof, pharmaceutical composition and method for treating
Inventor: CARTER BARRY HOWARD
IPC: C07H19/052
Filed: 1999-04-01
Abstract: 1. A crystalline form of Form II 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 degree . 2. A ethanol solvate 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 degree . 3. A crystalline form of Form V 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 degree . 4. A composition comprising an admixture of two or more crystalline forms or solvates of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in accordance with one of Claims 1-3. 5. A composition comprising crystalline form II of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in accordance with Claim 1 and amorphous 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole. 6. A composition comprising crystalline form I 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 7,90 +- 0,05, 10,39 +- 0,05, 14,63 +- 0,05, 15,79 +- 0,05, 20,75 +- 0,05, 21,99 +- 0,05, 22,77 +- 0,05, 24,14 +- 0,05, 24,71 +- 0,05 and 25,97 +- 0,05 degree , crystalline form V 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in accordance with Claim 3. 7. A pharmaceutical composition, comprising a compound according to any of Claims 1-3 and at least one pharmaceutically acceptable carrier for it. 8. 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in accordance with any of Claims 1-3 for therapeutic treatment. 9. A use of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in accordance with any of Claims 1-3 for preparation of medicament for treating viral infection. 10. A method for treating viral infection in human, when an effective antiviral amount of solvate or crystalline form 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in accordance with any of Claims 1-3 is administered to human-carrier. 11. A method for obtaining waterless crystalline form of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole comprises the following stages: a) dissolving 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in a form of free base or salt in suitable dissolvent; b) isolating 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole out of solution and, if desired, eliminate unconjugated dissolvent with obtaining 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in dry form. c) treating the obtained on stage b) compound with solubilizing dissolvent serving for transformation thereof into said waterless crystalline form of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole, and d) isolating said waterless crystalline form from the solution.