Prodrugs of 2,4-Pyrimidinediamine Compounds and Their Uses

A method of inhibiting the release and/or synthesis of cytokines in a cell, the method comprising contacting the cell with a metabolite of the compound of formula (I):

• or a salt, solvate, hydrate or N-oxide thereof, wherein:
• Y is O;
• Z1 and Z2 are each, independently of one another, CH or N;
• R2 is lower alkyl, lower cycloalkyl, lower heteroalkyl, lower cycloheteroalkyl, aryl, or a heteroaryl group, each of which is optionally substituted;
• R5 is halo, cyano, nitro, or trihalomethyl;
• R17 is hydrogen, halogen, fluoro, or lower alkyl or, alternatively, R17 taken together with R18 are an oxo (═O) group;
• R18 is hydrogen, halogen, fluoro, or lower alkyl, or, alternatively, R18 taken together with R17 are an oxo (═O) group;
• R19 hydrogen or lower alkyl, or, alternatively, R19 taken together with R20 are an oxo (═O) group;
• R20 is hydrogen or lower alkyl, or, alternatively, R20 taken together with R19 are an oxo (═O) group;
• R21, R22 and R23 are each, independently of one another, hydrogen or RP;
• R24 is hydrogen, lower alkyl or RP, with the proviso that at least one of R21, R22, R23 and R24 is RP;
• and
• each RP is, independently of the others, —(CRdRd)y—O—P(O)(ORi)(ORi), —(CRdRd)y—O—P(O)(ORi)(OH), —(CRdRd)y—O—P(ORi)(ORi) or —(CRdRd)y—O—P(ORi)(OH), where each Ri is, independently of the others, lower unsubstituted alkanyl, substituted or unsubstituted phenyl, or substituted or unsubstituted benzyl;
• each Rd is, independently of the other, hydrogen, cyano, optionally substituted (C1-C20) alkyl, (C1-C20) perfluoroalkyl, optionally substituted (C7-C30) arylalkyl or optionally substituted 6-30 membered heteroarylalkyl, where each optional substituent is, independently of the others, selected from hydrogen, alkyl, aryl, arylalkyl, heteroaryl and heteroalkyl, or, alternatively, two Rd taken together with the carbon atom to which they are bonded are a (C3-C5) cycloalkyl;
• and
• y is 1, 2, or 3, and
• wherein the metabolite is the product of cleavage of the Rp group from the compound of formula (I).