(e)-1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate for inhibiting cdk7

Abstract

or a pharmaceutically acceptable salt thereof.

We claim: 
     
         1 . A method for inhibiting cyclin-dependent kinase 7 activity in a patient, the method comprising administering to the patient in need thereof a therapeutically effective amount of a crystalline form of a salt of the compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein the salt is the chloride, besylate or edisylate salt. 
       
     
     
         2 . The method according to  claim 1 , wherein inhibiting cyclin-dependent kinase 7 activity in the patient treats cancer. 
     
     
         3 . The method of  claim 2 , wherein the cancer is selected from the group consisting of a glioma, a sarcoma, breast cancer, cervical cancer, colorectal cancer, gastric cancer, hematological cancer, hepatobiliary cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer, urothelial cancer, and uterine cancer. 
     
     
         4 . The method according to  claim 2 , wherein the cancer is selected from the group consisting of breast cancer, colorectal cancer, gastric cancer, lung cancer, and ovarian cancer. 
     
     
         5 . The method according to  claim 2 , wherein the compound is the S-enantiomer. 
     
     
         6 . The method according to  claim 3 , wherein the compound is the S-enantiomer. 
     
     
         7 . The method of treating cancer in a patient in need thereof, the method comprising:
 performing an in vitro assay using a biological sample from the patient;   determining the presence of at least one inactivating mutation in the ARID1A, KMT2C, KMT2D and RB1 genes, and   administering a therapeutically effective amount of [(3S)-1-[(E)-4-(dimethylamino)but-2-enoyl]pyrrolidin-3-yl]-4-[(3-isopropyl-5-methyl-pyrazolo[1,5-a]pyrimidin-7-yl)amino]piperidine-1-carboxylate in crystalline salt form to the patient, if at least one inactivating mutation in any of the genes is present.   
     
     
         8 . The method according to  claim 7 , wherein the cancer is selected from the group consisting of urothelial cancer, uterine cancer, colorectal cancer, breast cancer, lung cancer, ovarian cancer, gastric cancer, hepatobiliary cancer, pancreatic cancer, cervical cancers, prostate cancer, haemotological cancers, a sarcoma, skin cancers, and a glioma. 
     
     
         9 . The method according to  claim 8 , wherein:
 (a) the biological sample is a tumor sample; and   (b) the tumor sample is assayed by genomic sequencing or DNA sequencing.   
     
     
         10 . The method according to  claim 7 , wherein the crystalline salt form is the crystalline chloride salt. 
     
     
         11 . The method according to  claim 9 , wherein the crystalline salt form is the crystalline chloride salt. 
     
     
         12 . A pharmaceutically acceptable salt of [(3S)-1-[(E)-4-(dimethylamino)but-2-enoyl]pyrrolidin-3-yl]-4-[(3-isopropyl-5-methyl-pyrazolo[1,5-a]pyrimidin-7-yl)amino]piperidine-1-carboxylate in crystalline salt form, wherein the salt comprises the chloride salt. 
     
     
         13 . The salt according to  claim 12  which is characterized by a X-ray powder diffraction pattern having characteristic peaks using CuKa radiation, in 2θ±0.2°, at 18.9° in combination with one or more peaks selected from the group consisting of 5.5°, 15.5°, and 9.7°. 
     
     
         14 . The salt according to  claim 13  which is characterized by a X-ray powder diffraction pattern having characteristic peaks using CuKa radiation, in 2θ±0.2°, occurring at 18.9,° 5.5° 15.5° and 9.7°.