Natural product analogs including an anti-inflammatory cyanoenone pharmacore and methods of use

A compound comprising:

• a) the basic skeleton of an organic compound having two to eight five and/or six-membered rings provided that the basic skeleton is not the basic skeleton of argentatin, betulinic acid, lanostane, oleanic acid, boswellic acid, glycyrrhetinic acid, ursolic acid, or tricyclic-bis-enone;
• b) a structural unit of the formula:
• wherein:
• the carbon atoms labeled 1, 2 and 3 are part of a five or six-membered ring;
• X is cyano or —C(O)Ra, wherein Ra is:
• hydrogen, hydroxy, halo, amino, hydroxyamino, azido or mercapto;
• or
• alkyl(C≤12), alkenyl(C≤12), alkynyl(C≤12), aryl(C≤12), aralkyl(C≤12), heteroaryl(C≤12), heteroaralkyl(C≤12), alkoxy(C≤12), alkenyl-oxy(C≤12), alkynyloxy(C≤12), aryloxy(C≤12), aralkoxy(C≤12), heteroaryloxy(C≤12), heteroaralkoxy(C≤12), acyloxy(C≤12), alkylamino(C≤12), dialkylamino(C≤12), alkoxyamino(C≤12), alkenylamino(C≤12), alkynylamino(C≤12), arylamino(C≤12), aralkylamino(C≤12), heteroarylamino(C≤12), heteroaralkyl-amino(C≤12), alkylsulfonylamino(C≤12), amido(C≤12), alkyl-silyloxy(C≤12), or substituted versions of any of these groups;
• and
• R1 and R2 are each independently:
• hydrogen;
• or
• alkyl(C≤12), alkenyl(C≤12), alkynyl(C≤12), aryl(C≤12), aralkyl(C≤8), heteroaryl(C≤12), heteroaralkyl(C≤12), acyl(C≤12), alkoxy(C≤12), aryloxy(C≤12), aralkoxy(C≤12), heteroaryloxy(C≤12), hetero-aralkoxy(C≤12), acyloxy(C≤12), alkylamino(C≤12), dialkyl-amino(C≤12), arylamino(C≤12), aralkylamino(C≤12), hetero-arylamino(C≤12), heteroaralkylamino(C≤12), amido(C≤12), or a substituted version of any of these groups;
• or
• R1 and R2 are taken together and are alkanediyl(C≤12), alkenediyl(C≤12), alkanediyl(C≤12) or alkenediyl(C≤12);
• and
• c) from 0 to 8 chemical groups attached to a carbon atom of the basic skeleton other than carbon atoms 1, 2, 3 or 4, wherein each chemical group is independently:
• hydroxy, halo, oxo, amino, hydroxyamino, nitro, imino, cyano, azido, mercapto, or thio;
• or
• alkyl(C≤12), alkenyl(C≤12), alkynyl(C≤12), aryl(C≤12), aralkyl(C≤12), heteroaryl(C≤12), heteroaralkyl(C≤12), acyl(C≤12), alkylidene(C≤12), alkoxy(C≤12), alkenyloxy(C≤12), alkynyloxy(C≤12), aryloxy(C≤12), aralkoxy(C≤12), heteroaryloxy(C≤12), heteroaralkoxy(C≤12), acyl-oxy(C≤12), alkylamino(C≤12), dialkylamino(C≤12), alkoxyamino(C≤12), alkenylamino(C≤12), alkynylamino(C≤12), arylamino(C≤12), aralkyl-amino(C≤12), heteroarylamino(C≤12), heteroaralkylamino(C≤12), alkylsulfonylamino(C≤12), amido(C≤12), alkylimino(C≤12), alkenyl-imino(C≤12), alkynylimino(C≤12), arylimino(C≤12), aralkylimino(C≤12), heteroarylimino(C≤12), heteroaralkylimino(C≤12), acylimino(C≤12), alkylthio(C≤12), alkenylthio(C≤12), alkynylthio(C≤12), arylthio(C≤12), aralkylthio(C≤12), heteroarylthio(C≤12), heteroaralkylthio(C≤12), acyl-thio(C≤12), thioacyl(C≤12), alkylsulfonyl(C≤12), alkenylsulfonyl(C≤8), alkynylsulfonyl(C≤12), arylsulfonyl(C≤12), aralkylsulfonyl(C≤12), heteroarylsulfonyl(C≤12), heteroaralkylsulfonyl(C≤12), alkyl-ammonium(C≤12), alkylsulfonium(C≤12), alkylsilyl(C≤12), alkylsilyl-oxy(C≤12), or a substituted version of any of these groups;
• or pharmaceutically acceptable salts, esters, hydrates, solvates, tautomers, acetals, ketals, prodrugs, or optical isomers thereof.