Novel anthranilic amides and the use thereof

Abstract

Disclosed are anthranilic amide derivatives having the formula:Compositions are disclosed that include the anthranilic amide derivatives and the use of the anthranilic amide derivatives for the manufacture of a medicament. Further disclosed are methods of inhibiting or treating cancer, inhibiting or reversing an epithelial to mesenchymal cellular transition, and/or inhibiting MEK1/2 and/or MEK 5 enzymatic activity in a subject by administering to the subject an effective amount of a disclosed anthranilic amide derivative.

1 . A compound, having the formula: 
       
         
           
           
               
               
           
         
         wherein R 1  independently is: 
       
       
         
           
           
               
               
           
         
         a primary or tertiary amine group, a OR 11  group, or an amino acid group, and wherein the R 11  independently is a hydrogen, an alkyl, an alkene, or an alkyne group; wherein R 3 , R 5 , R 6 , R 9 , and R 10  are each independently a hydrogen, an alkyl, an alkene, an alkyne, a halogen, an alkoxy group with or without one or more carbon-carbon double or triple bonds, a cyano group, or a nitrile group; wherein R 2  and/or R 4  is/are independently a halogen group, and, when not a halogen group, R 2  or R 4  is a hydrogen group, and, when R 1  is a primary amine group or a OR 11  group, R 2  or R 4 , but not both, is a halogen group; and 
         wherein R 7  and R 8  are each independently a halogen group. 
       
     
     
         2 . The compound of  claim 1 , wherein R 1  is: 
       
         
           
           
               
               
           
         
       
     
     
         3 . (canceled) 
     
     
         4 . The compound of  claim 1 , wherein R 2  is a fluorine group. 
     
     
         5 . The compound of  claim 1 , wherein R 3 , R 5 , R 6 , R 9 , or R 10  is a hydrogen group or a halogen group. 
     
     
         6 . (canceled) 
     
     
         7 . The compound of  claim 1 , wherein R 4  is an iodine group. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The compound of  claim 9 , wherein R 6  is a fluorine group. 
     
     
         11 . (canceled) 
     
     
         12 . The compound of  claim 11 , wherein R 7  and/or R 8  is/are a fluorine group. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . The compound of  claim 1 , having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         17 . The composition of  claim 1  wherein the compound is selected from one of 3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid (SC-1-180), N,N-diethyl-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide (SC-1-65), 3,4-difluoro-2-((2-fluoro-4-iodophenyl) amino)-N,N-dimethylbenzamide (SC-1-69), 3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)-N-methylbenzamide (SC-1-72 amide), Tert-butyl-4-(3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoyl)piperazine-1-carboxylate (SC-1-75), (3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino) phenyl)(piperazin-1-yl)methanone, hydrochloride (SC-1-79), N-ethyl-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide (SC-1-80), N-(2-(dimethylamino)ethyl)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)-N-methylbenzamide hydrochloride (SC-1-122), 2-((2-fluoro-4-iodophenyl)amino)benzoic acid (SC-1-14 acid), (2-((2-fluoro-4-iodophenyl) amino)phenyl)(4-methylpiperazin-1-yl)methanone hydrochloride (SC-1-24 amide), 3,4-difluoro-2-((2-fluorophenyl)amino)benzoic acid (SC-2-25), 3,4-difluoro-2-((2-fluorophenyl) amino)benzamide (SC-2-37), 3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)(4-methylpiperazin-1-yl)methanone (24/IC-3-95/IC-D-122b), and 3,4-difluoro-2-((4-iodophenyl) amino)benzamide (?). 
     
     
         18 . A composition, comprising the compound of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         19 . The composition of  claim 18 , wherein the composition is formulated for oral, intravenous, intradermal, intramuscular, and subcutaneous administration. 
     
     
         20 . The composition of  claim 19 , wherein the composition comprises a product for oral delivery comprising a concentrate, a dried powder, a liquid, a capsule, a pellet, and a pill. 
     
     
         21 . Use of the compound of  claim 1  for the manufacture of a
 medicament. 
 
     
     
         22 . A method of inhibiting or treating cancer in a subject comprising: administering to the subject an effective amount of the compound of  claim 1 , thereby inhibiting or treating cancer. 
     
     
         23 . The method of  claim 22 , wherein the cancer comprises a solid tumor or metastatic cancer. 
     
     
         24 . The method of  claim 23 , wherein the solid tumor comprises a squamous cell carcinoma, prostate cancer, breast cancer, or pancreatic cancer. 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 24 , wherein the breast cancer comprises triple-negative breast cancer or early onset breast cancer. 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . A method of inhibiting or reversing an epithelial to mesenchymal cellular transition a subject comprising:
 administering to the subject an effective amount of the compound of  claim 1 , thereby inhibiting or reversing the epithelial to mesenchymal cellular transition.   
     
     
         32 . A method of inhibiting MEK1/2 and/or MEK 5 enzymatic activity in a subject
 comprising:
 administering to the subject an effective amount of the compound of  claim 1 , thereby inhibiting in MEK1/2 and/or MEK 5 enzymatic activity.