Solid state forms of substituted pyrazolopyrimidines and uses thereof

Abstract

The present disclosure relates to: a) solid state forms of a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III); b) pharmaceutical compositions comprising one or more solid state forms of a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III), and optionally, a pharmaceutically acceptable carrier or diluent; c) methods of treating tumors or cancers by administering one or more solid state forms of a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III) to a subject in need thereof; and d) methods for the preparation of solid state forms of a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III).

1 .- 74 . (canceled) 
     
     
         75 . A method for treating cancer comprising administering a solid state form of 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-1H-pyrazolo[3,4-d]pyrimidine of Formula (II): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, to a patient in need thereof. 
       
     
     
         76 . (canceled) 
     
     
         77 . (canceled) 
     
     
         78 . The method of  claim 75 , wherein the cancer is selected from DNA repair pathway deficient cancer, homologous recombination deficiency (HRD) cancer, BRCA1 mutant cancer, BRCA2 mutant cancer, PARP inhibitor refractory or resistant cancer, PARP inhibitor refractory or resistant BRCA1 or BRCA2 mutant cancer, hematological cancer, lymphatic cancer, cancer caused by a mutation in a gene encoding p53, ovarian cancer, breast cancer, non-small cell lung cancer (NSCLC), bone cancer, brain cancer, soft tissue cancer, kidney cancer, bladder cancer, skin cancer, lung cancer, and osteosarcoma. 
     
     
         79 . The method of  claim 75 , wherein the solid state form is substantially free of other polymorphic forms. 
     
     
         80 . The method of  claim 75 , wherein the solid state form is administered as a pharmaceutical composition comprising the solid state form and one or more pharmaceutically acceptable carriers or diluents. 
     
     
         81 . The method of  claim 75 , wherein the solid state form is a pharmaceutically acceptable co-crystal formed between 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-1H-pyrazolo[3,4-d]pyrimidine of Formula (II) and a pharmaceutically acceptable acid. 
     
     
         82 . The method of  claim 81 , wherein the pharmaceutically acceptable acid is selected from the group consisting of 1-hydroxy-2-naphthoic acid, 4-aminosalicylic acid, ascorbic acid, adipic acid, L-aspartic acid, benzene sulfonic acid, benzoic acid, trans-cinnamic acid, citric acid, ethanedisulfonic acid, fumaric acid, galactaric acid, gentisic acid, gluconic acid, D-glucuronic acid, glutamic acid, glutaric acid, glycolic acid, hexanoic acid, hippuric acid, hydrobromic acid, hydrochloric acid, lactic acid, maleic acid, L-malic acid, malonic acid, R-mandelic acid, methanesulfonic acid, mucic acid, naphthalene sulfonic acid, nicotinic acid, oxalic acid, palmitic acid, p-toluene sulfonic acid, phosphoric acid, propionic acid, saccharin, salicylic acid, stearic acid, succinic acid, sulfuric acid, L-tartaric acid, vanillic acid, vanillin, ethyl maltol, gallic acid, gallic acid ethyl ester, 4-hydroxybenzoic acid, 4-hydroxybenzoic acid methyl ester, 3,4,5-trihydroxybenzoic acid, nicotinamide, L-proline, and D-sorbitol. 
     
     
         83 . The method of  claim 81 , wherein the pharmaceutically acceptable acid is benzoic acid, and wherein the benzoic acid co-crystal is crystalline Form 8 characterized by an XRPD pattern having peaks at 12.1±0.2, 14.2±0.2, and 16.5±0.2 degrees two theta. 
     
     
         84 . The method of  claim 81 , wherein the pharmaceutically acceptable acid is salicylic acid, and wherein the salicylic acid co-crystal is crystalline Form 9 characterized by an XRPD pattern having peaks at 11.0±0.2, 16.5±0.2, 17.3±0.2 and 25.3±0.2 degrees two theta. 
     
     
         85 . The method of  claim 81 , wherein the solid state form is substantially free of other polymorphic forms. 
     
     
         86 . The method of  claim 81 , wherein the cancer is selected from DNA repair pathway deficient cancer, homologous recombination deficiency (HRD) cancer, BRCA1 mutant cancer, BRCA2 mutant cancer, PARP inhibitor refractory or resistant cancer, PARP inhibitor refractory or resistant BRCA1 or BRCA2 mutant cancer, hematological cancer, lymphatic cancer, cancer caused by a mutation in a gene encoding p53, ovarian cancer, breast cancer, non-small cell lung cancer (NSCLC), bone cancer, brain cancer, soft tissue cancer, kidney cancer, bladder cancer, skin cancer, lung cancer, and osteosarcoma. 
     
     
         87 . The method of  claim 81 , wherein the cancer is breast cancer. 
     
     
         88 . The method of  claim 81 , wherein the cancer is ovarian cancer. 
     
     
         89 . The method of  claim 81 , wherein the cancer is a BRCA1 mutant cancer or a BRCA2 mutant cancer. 
     
     
         90 . The method of  claim 81 , wherein the cancer is a PARP inhibitor refractory or resistant cancer. 
     
     
         91 . The method of  claim 81 , wherein the solid state form is administered as a pharmaceutical composition comprising the solid state form and one or more pharmaceutically acceptable carriers or diluents. 
     
     
         92 . The method of  claim 91 , wherein the pharmaceutical composition is an oral solid dosage form. 
     
     
         93 . The method of  claim 92 , wherein the oral solid dosage form is selected from a tablet, a capsule, a pill, granules, a powder, a sachet, a chewable, and a film. 
     
     
         94 . The method of  claim 75 , wherein the solid state form is a pharmaceutically acceptable salt formed between 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-1H-pyrazolo[3,4-d]pyrimidine of Formula (II) and a pharmaceutically acceptable acid. 
     
     
         95 . The method of  claim 94 , wherein the pharmaceutically acceptable acid is selected from the group consisting of 1-hydroxy-2-naphthoic acid, 4-aminosalicylic acid, ascorbic acid, adipic acid, L-aspartic acid, benzene sulfonic acid, benzoic acid, trans-cinnamic acid, citric acid, ethanedisulfonic acid, fumaric acid, galactaric acid, gentisic acid, gluconic acid, D-glucuronic acid, glutamic acid, glutaric acid, glycolic acid, hexanoic acid, hippuric acid, hydrobromic acid, hydrochloric acid, lactic acid, maleic acid, L-malic acid, malonic acid, R-mandelic acid, methanesulfonic acid, mucic acid, naphthalene sulfonic acid, nicotinic acid, oxalic acid, palmitic acid, p-toluene sulfonic acid, phosphoric acid, propionic acid, saccharin, salicylic acid, stearic acid, succinic acid, sulfuric acid, L-tartaric acid, vanillic acid, vanillin, ethyl maltol, gallic acid, gallic acid ethyl ester, 4-hydroxybenzoic acid, 4-hydroxybenzoic acid methyl ester, 3,4,5-trihydroxybenzoic acid, nicotinamide, L-proline, and D-sorbitol. 
     
     
         96 . The method of  claim 94 , wherein the pharmaceutically acceptable salt is a hydrochloric acid salt; and wherein the hydrochloric acid salt is crystalline Form 1 characterized by an XRPD pattern having peaks at 12.5±0.2, 22.4±0.2, and 23.9±0.2 degrees two theta. 
     
     
         97 . A method for treating cancer comprising administering a solid state form of 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-1H-pyrazolo[3,4-d]pyrimidine of Formula (II) of  claim 75  selected from the group consisting of:
 a) crystalline Form A, wherein Form A is characterized by an XRPD pattern having peaks at 14.3±0.2, 21.5±0.2, and 21.8±0.2 degrees two theta; 
 b) crystalline Form C, wherein Form C is characterized by an XRPD pattern having peaks at 14.2±0.2, 17.0±0.2, and 19.1±0.2 degrees two theta; 
 c) crystalline Form D, wherein Form D is characterized by an XRPD pattern having peaks at 13.9±0.2, 15.2±0.2, and 19.3±0.2 degrees two theta; 
 d) crystalline Form E, wherein Form E is characterized by an XRPD pattern having peaks at 10.6±0.2, 18.7±0.2, and 20.9±0.2 degrees two theta; and 
 e) crystalline Form F, wherein Form F is characterized by an XRPD pattern having peaks at 10.7±0.2, 14.3±0.2, and 21.8±0.2 degrees two theta; 
 
       or combinations thereof. 
     
     
         98 . The method of  claim 97 , wherein the solid state form is crystalline Form A, and wherein the solid state form is characterized by at least one of the following:
 a) an XRPD pattern as shown in  FIG.  1   ;   b) an endothermic peak at about 165° C., as determined by DSC;   c) a DSC profile as shown in  FIG.  2   ;   d) an about 0.93 wt % loss between room temperature and about 150° C., as determined by TGA; or   e) a TGA profile as shown in  FIG.  2   .   
     
     
         99 . The method of  claim 97 , wherein the solid state form is crystalline Form C, and wherein the solid state form is characterized by an XRPD pattern as shown in  FIG.  3   . 
     
     
         100 . The method of  claim 97 , wherein the solid state form is crystalline Form D, and wherein the solid state form is characterized by an XRPD pattern as shown in  FIG.  4   . 
     
     
         101 . The method of  claim 97 , wherein the solid state form is crystalline Form E, and wherein the solid state form is characterized by at least one of the following:
 a) an XRPD pattern as shown in  FIG.  5   ;   b) an endothermic peak at about 107° C., as determined by DSC;   c) a DSC profile as shown in  FIG.  6   ;   d) an about 13.5 wt % loss between room temperature and about 200° C., as determined by TGA; or   e) a TGA profile as shown in  FIG.  6   .   
     
     
         102 . The method of  claim 97 , wherein the solid state form is crystalline Form F, and wherein the solid state form is characterized by one of the following:
 a) an XRPD pattern as shown in  FIG.  25   ;   b) an endothermic peak at about 157° C., as determined by DSC; or   c) a DSC profile as shown in  FIG.  26   .   
     
     
         103 . A method for treating cancer comprising administering a pharmaceutically acceptable co-crystal formed between 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-(4-(1-isopropyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-1H-pyrazolo[3,4-d]pyrimidine of Formula (II): 
       
         
           
           
               
               
           
         
         and gentisic acid, to a patient in need thereof. 
       
     
     
         104 . The method of  claim 103 , wherein the gentisic acid co-crystal is crystalline Form 2 characterized by an XRPD pattern having peaks at 16.6±0.2, 18.7±0.2, and 22.5±0.2 degrees two theta. 
     
     
         105 . The method of  claim 103 , wherein the gentisic acid co-crystal is characterized by an endothermic peak at about 186.0° C., as determined by DSC. 
     
     
         106 . The method of  claim 103 , wherein the gentisic acid co-crystal is characterized by an about 3.17 wt % loss between room temperature and about 170° C., as determined by TGA. 
     
     
         107 . The method of  claim 103 , wherein the gentisic acid co-crystal is characterized by at least one of the following:
 a) an XRPD pattern as shown in  FIG.  9   ;   b) a DSC profile as shown in  FIG.  10   ; or   c) a TGA profile as shown in  FIG.  10   .   
     
     
         108 . The method of  claim 103 , wherein the cancer is selected from DNA repair pathway deficient cancer, homologous recombination deficiency (HRD) cancer, BRCA1 mutant cancer, BRCA2 mutant cancer, PARP inhibitor refractory or resistant cancer, PARP inhibitor refractory or resistant BRCA1 or BRCA2 mutant cancer, hematological cancer, lymphatic cancer, cancer caused by a mutation in a gene encoding p53, ovarian cancer, breast cancer, non-small cell lung cancer (NSCLC), bone cancer, brain cancer, soft tissue cancer, kidney cancer, bladder cancer, skin cancer, lung cancer, and osteosarcoma. 
     
     
         109 . The method of  claim 103 , wherein the cancer is breast cancer. 
     
     
         110 . The method of  claim 103 , wherein the cancer is ovarian cancer. 
     
     
         111 . The method of  claim 103 , wherein the cancer is a BRCA1 mutant cancer or a BRCA2 mutant cancer. 
     
     
         112 . The method of  claim 103 , wherein the cancer is a PARP inhibitor refractory or resistant cancer. 
     
     
         113 . The method of  claim 103 , wherein the cancer is breast cancer or ovarian cancer, and wherein the cancer is a PARP inhibitor refractory or resistant cancer and/or a BRCA1 mutant cancer or a BRCA2 mutant cancer. 
     
     
         114 . The method of  claim 103 , wherein the solid state form is administered as a pharmaceutical composition comprising the solid state form and one or more pharmaceutically acceptable carriers or diluents. 
     
     
         115 . The method of  claim 114 , wherein the pharmaceutical composition is an oral solid dosage form. 
     
     
         116 . The method of  claim 115 , wherein the oral solid dosage form is selected from a tablet, a capsule, a pill, granules, a powder, a sachet, a chewable, and a film. 
     
     
         117 . The method of  claim 116 , wherein the solid state form is substantially free of other polymorphic forms. 
     
     
         118 . The method of  claim 108 , wherein the solid state form is administered as a pharmaceutical composition comprising the solid state form and one or more pharmaceutically acceptable carriers or diluents. 
     
     
         119 . The method of  claim 118 , wherein the pharmaceutical composition is an oral solid dosage form. 
     
     
         120 . The method of  claim 119 , wherein the oral solid dosage form is selected from a tablet, a capsule, a pill, granules, a powder, a sachet, a chewable, and a film. 
     
     
         121 . The method of  claim 120 , wherein the solid state form is substantially free of other polymorphic forms.