Cycloalkyl substituted pyrimidinediamine compounds and their uses

A compound according to structural formula (I):

• or a salt or N-oxide thereof, wherein:
• R2 is a (C6-C20)aryl, 5-20 membered heteroaryl, (C7-C28)arylalkyl or 6-28 membered heteroarylalkyl group, each optionally substituted with one or more of the same or different R8 groups;
• R4 is a saturated or unsaturated, bridged (C3-C16)cycloalkyl ring substituted with an R7 group;
• R5 is selected from hydrogen, (C1-C8)allyl optionally substituted with one or more of the same or different R8 groups, and an electronegative group;
• and
• R7 is —C(O)ORd or —C(O)NRdRd,
• wherein
• the electronegative group is selected from the group consisting of —CN, —NC, —NO2, halo, (C1-C3)haloalkyl, (C1-C3)perhaloalkyl, (C1-C3)fluoroalkyl, (C1-C3)perfluoroalkyl, —CF3, (C1-C3)haloalkoxy, (C1-C3)perhaloalkoxy, (C1-C3)fluoroalkoxy, (C1-C3)perfluoroalkoxy, —OCF3, —C(O)Ra, —C(O)ORa, —C(O)CF3, and —C(O)OCF3;
• each R8 group is, independently of the others, selected from a water-solubilizing group, Ra, Rb, (C3-C8)cycloalkyl optionally substituted with one or more of the same or different Ra and/or Rb groups, lower heterocycloalkyl optionally substituted with one or more of the same or different Ra and/or Rb groups, (C1-C8)alkoxy optionally substituted with one or more of the same or different Rb groups and —O—(CH2)x—Rb, where x is an integer ranging from 1 to 6;
• each Ra is, independently of the others, selected from hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C6-C14)aryl, naphthyl, (C7-C20)arylalkyl and benzyl;
• each Rb is, independently of the others, selected from ═O, —ORa, (C1-C3) haloalkyloxy, —OCF3, ═S, —SRa, ═NRa, ═NORa, —NRcRc, halogen, —CF3, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)Ra, —S(O)2Ra, —S(O)2ORa, —S(O)NRaRa, —S(O)2NRcRc, —OS(O)Ra, —OS(O)2Ra, —OS(O)2ORa, —OS(O)2NRcRc, —C(O)Ra, —C(O)ORa, —C(O)NRcRc, —C(NH)NRcRc, —C(NRa)NRcRc, —C(NOH)Ra, —C(NOH)NRcRc, —OC(O)Ra, —OC(O)ORa, —OC(O)NRcRc, —OC(NH)NRcRc and —OC(NRa)NRcRc;
• each Rc is, independently of the others, selected from Ra or, alternatively, two Rc that are bonded to the same nitrogen atom may be taken together with this nitrogen atom to form a 5-8 membered heterocycloalkyl group which may optionally include from 1 to 3 additional heteroatomic groups selected from O, S, N—(CH2)y—Ra, N—(CH2)y—C(O)Ra, N—(CH2)y—C(O)ORa, N—(CH2)y—S(O)2Ra, N—(CH2)y—S(O)2ORa and N—(CH2)y—C(O)NRaRa, where y is an integer ranging from 0 to 6, and which may optionally include one or more of the same or different R8 and/or (C1-C8)alkyl substituents;
• and
• each Rd is, independently of the others, selected from Ra, Rc and a chiral auxiliary group;
• and
• the water-solubilizing group is of the formula:
• morpholino, piperidinyl, (C1-C6)N-alkyl piperidinyl, N-methyl piperidinyl, piperazinyl, (C1-C6)N-alkylpiperazinyl, N-methylpiperazinyl, N-ethyl piperidinyl, N-ethyl piperazinyl, pyrrolidinyl, N-alkyl pyrrolidinyl, N-methyl pyrrolidinyl, diazepinyl, N-ethyl pyrrolidinyl, N-alkyl azepinyl, N-methyl azepinyl, N-ethyl azepinyl, homopiperazinyl, N-methyl homopiperazinyl, N-ethyl homopiperazinyl, imidazoyl, where Y is selected from CH and N, Z is selected from CH2, O, S, N, NH, N—(CH2)y—Ra, N—(CH2)y—C(O)Ra, N—(CH2)y—C(O)ORa, N—(CH2)y—S(O)2Ra, N—(CH2)y—S(O)2ORa and N—(CH2)y—C(O)NRcRc, with the proviso that Y and Z are not both simultaneously CH and CH2, respectively;
• and
• the chiral auxiliary group is
• wherein R9 is hydrogen or (C1-C8) alkyl.