Small Molecule Agonists and Antagonists of NR2F6 Activity in Humans

Abstract

The present technology is directed to modulators of nuclear receptor activity, specifically to the modulation of NR2F6 activity and NR2F6 utilizing compounds, and the immune modulation and modulation of cancer stem cell activity through administration of compounds described herein to humans.

1 . A pharmaceutical composition comprising a pharmaceutical compound in solid form having a structure selected from the group consisting of Formulas (III) and (VI), or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient, diluent, or carrier,
 wherein in a said pharmaceutical compound having a structure of Formula (III)   
       
         
           
           
               
               
           
         
         Q is a halogen, an alkyl group, a substituted alkyl group, a cyclic alkyl group, an aryl group, a substituted aryl group, a heterocyclic group, an ester, an aldehyde, a ketone, a carboxylic acid, an amide, an amine, an ether, a thiol, a nitrile, or NO2, and R1 is a mono-substitution or a di-substitution with H, a halogen, two halogens, a methyl group, two methyl groups, a butyl group, a substituted alkyl group comprising at least one oxygen, two substituted alkyl groups comprising at least one oxygen, a halogen and an alkyl group, a cyclic alkyl group, an aryl group, a substituted aryl group, a heterocyclic group, an ester, an aldehyde, a ketone, a carboxylic acid, an amide, an amine, an ether, or a nitrile, and 
         wherein in a said pharmaceutical compound having a structure of Formula (VI) 
       
       
         
           
           
               
               
           
         
         any of Q1 and Q2 is a halogen, an alkyl group, a substituted alkyl group, methoxy, a cyclic alkyl group, an aryl group, a substituted aryl group, a heterocyclic group, an ester, an aldehyde, a ketone, a carboxylic acid, an amide, an amine, an ether, a thiol or a nitrile and R1 is a mono-substitution or a di-substitution with a halogen, an alkyl group, two alkyl groups, a substituted alkyl group, two substituted alkyl groups, a halogen and an alkyl group, a cyclic alkyl group, an aryl group, a substituted aryl group, a heterocyclic group, an ester, an aldehyde, a ketone, a carboxylic acid, an amide, an amine, an ether, or a nitrile. 
       
     
     
         2 . The pharmaceutical composition of  claim 1  in an oral dosage form. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical compound having a structure of Formula (III) is selected from the group consisting of: a compound wherein Q is F, Cl, or Br, and R1 is 2-F, 3-F, 4-F, 3,5-diF, 3-CI, 4-CI, 3,4-diCI, 4-Br, 3-C1-4-F, 4-Me, 3,4-diMe, 3,5-diMe, 3-MeO, 4-MeO, 3,4-diMeO, 4-t-Bu, 3-C1-4-Me, 3-CH3-4-F, or 3-CN, a compound wherein Q is MeOOCH2 and R1 is selected from H, 2-F, 3-F, 4-F, 3,5-diF, 3-CI, 4-CI, 3,4-diCI, 4-Br, 3-C1-4-F, 4-Me, 3,4-diMe, 3,5-diMe, 3-MeO, 4-MeO, 3,4-diMeO, 4-t-Bu, 3-C1-4-Me, 3-CH3-4-F, and 3-CN, a compound wherein Q is MeO and R1 is selected from H, 2-F, 3-F, 4-F, 3,5-diF, 3-CI, 4-CI, 3,4-diCI, 4-Br, 3-CI-4-F, 4-Me, 3,4-diMe, 3,5-diMe, 3-MeO, 4-MeO, 3,4-diMeO, 4-t-Bu, 3-C1-4-Me, 3-CH3-4-F, and 3-CN, and a compound wherein Q is NO2 and R1 is selected from H, 2-F, 3-F, 4-F, 3,5-diF, 3-CI, 4-CI, 3,4-diCI, 4-Br, 3-C1-4-F, 4-Me, 3,4-diMe, 3,5-diMe, 3-MeO, 4-MeO, 3,4-diMeO, 4-t-Bu, 3-C1-4-Me, 3-CH3-4-F, and 3-CN. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the pharmaceutical compound having a structure of Formula (III) is selected from the group consisting of:
 Compound C11 wherein Q is MeOOCH2, R1 is H,   Compound C14 wherein Q is MeOOCH2, R1 is 4-F,   Compound C154 wherein Q is Br, R1 is 3,4-diMeO,   Compound C155 wherein Q is Cl, R1 is 3,4-diMeO,   Compound C157 wherein Q is NO2, R1 is 3,4-diMeO,   Compound C195 wherein Q is Cl, R1 is 3-CN, and   Compound C210 wherein Q is NO2, R1 is H.   
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical compound having a structure of Formula (IV) is selected from the group consisting of a compound wherein any of Q1 and Q2 is F, Cl, Br, or methoxy (OMe), and R1 is OMe, 3,4-di-Me, 4-Cl, 3,4-di-Cl, 4-OMe, 4-Br, 4-t-Bu, 3-Me-4-F, or 4-F. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the pharmaceutical compound having a structure of Formula (VI) is selected from the group consisting of:
 Compound C289 wherein Q1 is F, Q2 is F, R1 is 4-OMe, and   Compound C290 wherein Q1 is F, Q2 is F, R1 is 4-Br.