POLYMORPHIC FORMS OF MACROCYCLIC HCV INHIBITOR Russian patent published in 2014 - IPC C07D417/04 A61K31/465 

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a crystalline form of a solid-state compound of formula

having an X-ray powder diffraction characterised by peaks as follows: (i) 8.5°±0.2°, 10.7°±0.2°, 13.7°±0.2°, 14.8°±0.2° and 17.1°±0.2° at a diffraction angle, two theta (form I); (ii) 4.6°±0.2°, 6.5°±0.2°, 10.2°±0.2°, 12.9°±0.2° and 14.4°±0.2° at a diffraction angle, two theta (form II); (iii) 6.5°±0.2°, 9.8°±0.2° and 17.8°±0.2° at a diffraction angle, two theta (form III); (iv) 5.6°±0.2°, 9.6°±0.2°, 11.8°±0.2°, 15.9°±0.2° and 17.1°±0.2° at a diffraction angle, two theta (form IV); (v) 9.6°±0.2° and 19.0°±0.2° at a diffraction angle, two theta (form V); (vi) 4.4°±0.2°, 6.5°±0.2°, 9.9°±0.2°, 10.5°±0.2° and 12.9°±0.2° at a diffraction angle, two theta (form VI). The invention also refers to a mixture of two or more crystalline forms I, II, III, IV, V and VI of the compound of formula (I) for treating HCV and to a mixture of two or more crystalline forms I, II, III, IV, V and VI of the compound of formula (I) and an amorphic form of the compound of formula (I) for treating HCV. The crystalline form (I) is prepared by: a) boiling the mixture of polymorphs I and II in 1-butanol or 2-propanol in a back flow condenser to produce a transparent solution; and b) spontaneous cooling of the solution to a room temperature while stirring, and then filtering and recovering crystalline form I. The method for preparing crystalline form II involves: a) preparing a suspension of the amorphic form of the compound of formula (I) in isopropanol; b) mixing the suspension at a room temperature; and c) fusing the suspension with fusing crystals of form II or form I while stirring, then filtering and drying at 60°C. There are also presented versions of the method for preparing the crystalline form (I) and (II) and forms (III), (IV) (V) and (VI). Besides, the invention refers to a pharmaceutical composition for treating HCV containing the crystalline form of the compound of formula (I), the mixture of two or more crystalline forms of the compound of formula (I) and a pharmaceutically acceptable excipient.

EFFECT: crystalline form of the hepatitis C virus (HCV) serine protease inhibitor.

19 cl, 15 dwg, 6 tbl, 12 ex