Salts and crystall forms of 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile

Abstract

The invention relates to particular crystalline forms of 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile, its hydrates and solvates, its salts and hydrates and solvates of its salts, certain processes for their preparation, pharmaceutical compositions containing these crystalline forms, and their use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans, and their use as an intermediate or for the preparation of pharmaceutical preparations for use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans.

What is claimed is: 
     
         1 . A crystalline form of the compound of formula I 
       
         
           
           
               
               
           
         
         or of a hydrate or solvate of the compound of formula I, or of a salt of the compound of formula I, or of a hydrate or solvate of a salt of the compound of formula I. 
       
     
     
         2 . Compound I according to  claim 1  in crystalline form A. 
     
     
         3 . A compound according to  claim 2  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 8.4°+/−0.3°. 
     
     
         4 . Compound I according to  claim 1  in crystalline form B. 
     
     
         5 . A compound according to  claim 3  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 6.9°+/−0.3°. 
     
     
         6 . Compound I according to  claim 1  in crystalline form C. 
     
     
         7 . A compound according to  claim 6  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 14.7°+/−0.3°. 
     
     
         8 . Compound I according to  claim 1  in crystalline form D. 
     
     
         9 . A compound according to  claim 8  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 23.9°+/−0.3°. 
     
     
         10 . A monohydrate of compound 1 according to  claim 1  in crystalline form H A . 
     
     
         11 . A compound according to  claim 10  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 17.6°+/−0.3°. 
     
     
         12 . A monotosylate salt of compound I according to  claim 1  in crystalline form. 
     
     
         13 . A monotosylate salt of compound I according to  claim 12  in crystalline form A. 
     
     
         14 . A compound according to  claim 12  or  13  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.7°+/−0.3°. 
     
     
         15 . A compound according to  claim 12 ,  13  or  14  which shows on X-ray diffraction peaks at an angle of diffraction 2Theta of 5.4°+/−0.3°; 5.7°+/−0.3° and 17.2°+/−0.3°. 
     
     
         16 . A compound according to  claim 12  or  13  which shows an X-ray diffraction diagram essentially as outlined in  FIG. 6 . 
     
     
         17 . A monotosylate salt of compound I according to  claim 12  in crystalline form B. 
     
     
         18 . A compound according to  claim 12  or  17  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.8°+/−0.3°. 
     
     
         19 . A compound according to  claim 12 ,  17  or  18  which shows on X-ray diffraction peaks at an angle of diffraction 2Theta of 5.8°+/−0.3°; 17.8°+/−0.3° and 18.7°+/−0.3°. 
     
     
         20 . A monohydrate of the monotosylate salt of compound I according to  claim 1  in crystalline form H A . 
     
     
         21 . A compound according to  claim 20  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 6.5°+/−0.3°. 
     
     
         22 . A dihydrate of the monotosylate salt of compound I according to  claim 1  in crystalline form H B . 
     
     
         23 . A compound according to  claim 22  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 6.9°+/−0.3°. 
     
     
         24 . A diformic acid solvate of the monotosylate salt of compound I according to  claim 1  in crystalline form S A . 
     
     
         25 . A compound according to  claim 24  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.8°+/−0.3°. 
     
     
         26 . A ditosylate salt of compound I according to  claim 1  in crystalline form. 
     
     
         27 . A ditosylate salt of compound I according to  claim 26  in crystalline form A. 
     
     
         28 . A compound according to  claim 26  or  27  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 22.4°+/−0.3°. 
     
     
         29 . A trihydrate of the ditosylate salt of compound I according to  claim 1  in crystalline form H A . 
     
     
         30 . A compound according to  claim 29  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 4.7°+/−0.3°. 
     
     
         31 . An amorphous monotosylate salt of compound I according to  claim 1 . 
     
     
         32 . A monohydrate of the diformic acid solvate of the monotosylate salt of compound I according to  claim 1  in crystalline form S C . 
     
     
         33 . A compound according to  claim 32  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.6°+/−0.3°. 
     
     
         34 . A diacetic acid solvate of the monotosylate salt of compound I according to  claim 1  in crystalline form S B . 
     
     
         35 . A compound according to  claim 34  which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.7°+/−0.3°. 
     
     
         36 . The solid form of the compound of formula I or of a hydrate or solvate of the compound of formula I, or of a salt of the compound of formula I, or of a hydrate or solvate of a salt of the compound of formula I according to any one of the  claims 1  to  35 , which is present in essentially pure form. 
     
     
         37 . A pharmaceutical composition comprising a solid form of the compound of formula I, its hydrates or solvates, its salts and hydrates or solvates of its salts according to any one of the  claims 1  to  35 , and optionally at least one pharmaceutically acceptable carrier. 
     
     
         38 . The use of a solid form of the compound of formula I, its hydrates or solvates, its salts and hydrates or solvates of its salts according to any one of the  claims 1  to  35  for the preparation of a medicament for the treatment of treatment of a proliferative disease selected from a benign or malignant tumor, carcinoma of the brain, kidney, liver, adrenal gland, bladder, breast, stomach, gastric tumors, ovaries, colon, rectum, prostate, pancreas, lung, vagina or thyroid, sarcoma, glioblastomas, multiple myeloma or gastrointestinal cancer, especially colon carcinoma or colorectal adenoma or a tumor of the neck and head, an epidermal hyperproliferation, psoriasis, prostate hyperplasia, a neoplasia, a neoplasia of epithelial character, lymphomas, a mammary carcinoma or a leukemia. Other diseases include Cowden syndrome, Lhermitte-Dudos disease and Bannayan-Zonana syndrome, or diseases in which the PI3k/PKB pathway is aberrantly activated. 
     
     
         39 . Method of treating a disease selected from a benign or malignant tumor, carcinoma of the brain, kidney, liver, adrenal gland, bladder, breast, stomach, gastric tumors, ovaries, colon, rectum, prostate, pancreas, lung, vagina or thyroid, sarcoma, glioblastomas, multiple myeloma or gastrointestinal cancer, especially colon carcinoma or colorectal adenoma or a tumor of the neck and head, an epidermal hyperproliferation, psoriasis, prostate hyperplasia, a neoplasia, a neoplasia of epithelial character, lymphomas, a mammary carcinoma or a leukemia. Other diseases include Cowden syndrome, Lhermitte-Dudos disease and Bannayan-Zonana syndrome, or diseases in which the PI3K/PKB pathway is aberrantly activated in a warm-blooded animal in need thereof comprising administering to the animal a crystalline form of the compound of formula I, its hydrates or solvates, its salts or hydrates or solvates of its salts according to any one of the  claims 1  to  35  in a quantity which is therapeutically effective against the respective disease.