Methods and uses of colchicine derivatives

A method for treating neutrophil-driven inflammation in a mammal, comprising administering to the mammal in need thereof a therapeutically effective amount of a compound of Formula I:

• wherein:
• Z is O or S;
• X1 is OR10 and R10 is selected from a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, or C2-C6 alkynyl or X1 is —CR4R5R6, wherein R4 and R5 are each independently selected from H, or substituted or unsubstituted alkyl, and R6 is —NR(CO)CR7R8R9, wherein R is selected from H and a substituted or unsubstituted alkyl, and R7, R8, and R9 are each selected from H, halo group, and a substituted or unsubstituted alkyl;
• R2 and R3 are each independently selected from a substituted or unsubstituted alkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted alkylaryl;
• Wherein the substituents are selected from a group consisting of cycloalkyl, heterocyclyl, hydroxyalkyl, benzyl, carbonyl, halo, haloalkyl, perfluoroalkyl, perfluoroalkoxy, alkyl, alkenyl, alkynyl, hydroxy, oxo, mercapto, alkylthio, alkoxy, aryl or heteroaryl, aryloxy or heteroaryloxy, aralkyl or heteroaralkyl, aralkoxy or heteroaralkoxy, HO—(C═O)—, amido, amino, alkyl- and dialkylamino, cyano, nitro, carbamoyl, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, ialkylaminocarbonyl, arylcarbonyl, aryloxycarbonyl, alkylsulfonyl, and arylsulfonyl;
• a pharmaceutically-acceptable salt thereof, hydrate thereof, solvate thereof, tautomer thereof, optical isomer thereof, or combination thereof;
• wherein the compound of Formula I inhibits production of an inflammatory mediator at a lower dose than colchicine;
• and wherein the neutrophil-driven inflammation is associated with pseudogout, gout, cardiovascular disease, vasculitis, or combinations thereof.