A-ring epoxidized triterpenoid-based anti-inflammation modulators and methods of use thereof

A compound of the formula:

• wherein:
• n is 1 or 2;
• X1 and X2 are independently hydrogen, hydroxy or oxo, provided that X1 is not oxo when carbon atoms 12 and 13 are connected to one another with a double bond, further provided that X2 is not oxo when carbon atoms 9 and 11 are connected to one another with a double bond;
• R1 is hydrogen, hydroxy, amino, cyano, halo, or —C(O)Ra, wherein Ra is hydrogen, hydroxy, amino, alkyl(C1-4), alkoxy(C1-4), alkylamino(C1-4), dialkylamino(C≦8), or alkylsulfonylamino(C1-4);
• R2 and R2′ are each independently hydrogen, alky(C≦8), or substituted alkyl(C≦8);
• R3 and R4 are each independently hydrogen, methyl or as defined below when either of these groups is taken together with group Rc;
• and
• R5, R6, R7 and R8 are each independently:
• hydrogen;
• or
• alkyl(C≦6), alkenyl(C≦6), acyl(C≦6) or a substituted version of either of these groups;
• Y is:
• hydrogen, hydroxy, amino, cyano, halo, or mercapto;
• or
• alkyl(C≦8), alkenyl(C≦8), alkynyl(C≦8), aryl(C≦12), aralkyl(C≦12), heteroaryl(C≦8), heterocycloalkyl(C≦12), alkoxy(C≦8), aryloxy(C≦12), acyloxy(C≦8), alkylamino(C≦8), dialkylamino(C≦8), alkenylamino(C≦8), arylamino(C≦8), aralkylamino(C≦8), alkylthio(C≦8), acylthio(C≦8), alkylsulfonylamino(C≦8), or substituted versions of any of these groups;
• or
• -alkanediyl(C≦8)-Rb, wherein the alkanediyl(C≦8) group is either substituted or unsubstituted and Rb is:
• hydroxy, halo, or amino;
• or
• heteroaryl(C≦8), alkoxy(C≦8), alkenyloxy(C≦8), aryloxy(C≦8), aralk-oxy(C≦8), heteroaryloxy(C≦8), acyloxy(C≦8), alkylamino(C≦8), dialkylamino(C≦8), arylamino(C≦8), aralkylamino(C≦8), heteroarylamino(C≦8), alkylsulfonyl-amino(C≦8), amido(C≦8), or a substituted version of any of these groups;
• or
• —(CH2)mC(O)Rc, wherein m is 0-6 and Rc is:
• hydrogen, hydroxy, halo, amino, or mercapto;
• or
• alkyl(C≦8), alkenyl(C≦8), alkynyl(C≦8), aryl(C≦8), aralkyl(C≦8), hetero-aryl(C≦8), heterocycloalkyl(C≦8), alkoxy(C≦8), aryloxy(C≦8), aralkoxy(C≦8), acyloxy(C≦8), alkylamino(C≦8), dialkyl-amino(C≦8), arylamino(C≦8), or a substituted version of any of these groups;
• or
• Rc and R3, taken together, are —O— or —NRd—, wherein Rd is hydrogen or alkyl(C≦4);
• or
• Rc and R4, taken together, are —O— or —NRd—, wherein Rd is hydrogen or alkyl(C≦4);
• or
• —NHC(O)Re, wherein Re is:
• hydrogen, hydroxy, amino;
• or
• alkyl(C≦8), alkenyl(C≦8), alkynyl(C≦8), aryl(C≦8), aralkyl(C≦8), hetero-aryl(C≦8), heterocycloalkyl(C≦8), alkoxy(C≦8), aryloxy(C≦8), aralkoxy(C≦8), heteroaryloxy(C≦8), acyloxy(C≦8), alkyl-amino(C≦8), dialkylamino(C≦8), arylamino(C≦8), or a substituted version of any of these groups;
• or a pharmaceutically acceptable salt thereof.