Kras g12c inhibitors and methods of using the same

Abstract

Provided herein are methods of using KRAS G12C inhibitors and compositions of the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.

What is claimed is: 
     
         1 . A method of treating cancer, the method comprising: administering to a cancer patient a compound having a structure selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof a pharmaceutically acceptable salt of the stereoisomer thereof or a pharmaceutically acceptable salt of the atropisomer thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the cancer is lung cancer, pancreatic cancer, endometrial cancer, appendix cancer, small intestine cancer or colorectal cancer. 
     
     
         3 . The method of  claim 1 , wherein the lung cancer is non-small cell lung cancer. 
     
     
         4 . The method of  claim 1 , wherein the cancer is colorectal cancer. 
     
     
         5 . The method of  claim 1 , wherein the cancer is pancreatic cancer. 
     
     
         6 . The method of  claim 1 , wherein the cancer is endometrial cancer. 
     
     
         7 . The method of  claim 1 , wherein the cancer is appendix cancer. 
     
     
         8 . The method of  claim 1 , wherein the cancer is small intestine cancer. 
     
     
         9 . The method of  claim 1 , wherein the cancer is a KRAS G12C mutated cancer. 
     
     
         10 . The method of  claim 1 , further comprising administering to the patient in need thereof a therapeutically effective amount of an additional pharmaceutically active compound. 
     
     
         11 . The method of  claim 10 , wherein the additional pharmaceutically active compound is an anti-PD-1 agent. 
     
     
         12 . The method of  claim 10 , wherein the anti-PD-1 agent is BMS-936559. 
     
     
         13 . The method of  claim 10 , wherein the anti-PD-1 antagonist is MK 3475. 
     
     
         14 . The method of  claim 10 , wherein the additional pharmaceutically active compound is a MEK inhibitor. 
     
     
         15 . A method of treating cancer, the method comprising: administering to a cancer patient a compound having a structure: 
       
         
           
           
               
               
           
         
         or the stereoisomer thereof, the atropisomer thereof, the pharmaceutically acceptable salt thereof, the pharmaceutically acceptable salt of the stereoisomer thereof, or the pharmaceutically acceptable salt of the atropisomer thereof. 
       
     
     
         16 . The method of  claim 15 , wherein the cancer is lung cancer, pancreatic cancer, endometrial cancer, appendix cancer, small intestine cancer or colorectal cancer. 
     
     
         17 . The method of  claim 15 , wherein the lung cancer is non-small cell  - 3g cancer. 
     
     
         18 . The method of  claim 15 , wherein the cancer is colorectal cancer. 
     
     
         19 . The method of  claim 15 , wherein the cancer is pancreatic cancer. 
     
     
         20 . The method of  claim 15 , wherein the cancer is endometrial cancer. 
     
     
         21 . The method of  claim 15 , wherein the cancer is appendix cancer. 
     
     
         22 . The method of  claim 15 , wherein the cancer is small intestine cancer. 
     
     
         23 . The method of  claim 15 , wherein the cancer is a KRAS G12C mutated cancer. 
     
     
         24 . The method of  claim 15 , further comprising administering to the patient in need thereof a therapeutically effective amount of an additional pharmaceutically active compound. 
     
     
         25 . The method of  claim 24 , wherein the additional pharmaceutically active compound is an anti-PD-1 agent. 
     
     
         26 . The method of  claim 24 , wherein the anti-PD-1 agent is BMS-936559. 
     
     
         27 . The method of  claim 24 , wherein the anti-PD-1 antagonist is MK 3475. 
     
     
         28 . The method of  claim 24 , wherein the additional pharmaceutically active compound is a MEK inhibitor. 
     
     
         29 . A kit for treating cancer, the kit comprising:
 a compound having the structure   
       
         
           
           
               
               
           
         
       
       or the stereoisomer thereof, the atropisomer thereof, the pharmaceutically acceptable salt thereof, the pharmaceutically acceptable salt of the stereoisomer thereof, or the pharmaceutically acceptable salt of the atropisomer thereof; and an additional pharmaceutical active compound. 
     
     
         30 . The kit of  claim 29 , wherein the cancer is non-small cell lung cancer. 
     
     
         31 . The kit of  claim 29 , wherein the cancer is colorectal cancer. 
     
     
         32 . The kit of  claim 29 , wherein the cancer is pancreatic cancer. 
     
     
         33 . The kit of  claim 29 , wherein the cancer is endometrial cancer. 
     
     
         34 . The kit of  claim 29 , wherein the cancer is appendix cancer. 
     
     
         35 . The kit of  claim 29 , wherein the cancer is small intestine cancer. 
     
     
         36 . The kit of  claim 29 , wherein the cancer is a KRAS G12C mutated cancer.