Cycloalkyl substituted pyrimidinediamine compounds and their uses
The present disclosure provides 2,4-pyrimidinediamine compounds having antiproliferative activity, compositions comprising the compounds and methods of using the compounds to inhibit cellular proliferation and to treat proliferate diseases such as tumorigenic cancers.
1. A method of inhibiting an Aurora kinase in a cell, the method comprising contacting the cell with an effective amount of a compound according to structural formula (I):
or an active salt or N-oxide thereof, wherein:
R 2 is an optionally substituted heteroaryl, or heteroarylalkyl group;
R 4 is a saturated or unsaturated, bridged or unbridged cycloalkyl ring including an R 7 substituent, with the proviso that when the cycloalkyl ring is a saturated bridged cycloalkyl, or an unsaturated bridged or unbridged cycloalkyl, this R 7 substituent is optional;
R 5 is selected from hydrogen, an optionally substituted lower alkyl and a group selected from the group consisting of —CN, —NC, —NO 2 , 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, —OCF 3 , OC(O)R a , —C(O)OR a , —C(O)CF 3 , and —C(O)CF 3 ;
R 7 is an amide or an ester group,
wherein each R a is independently selected from hydrogen, lower alkyl, lower cycloalkyl, (C6-C14) aryl, phenyl, naphthyl, (C7-C20) arylalkyl and benzyl.
2. The method according to claim 1 wherein the cell is a human cancer cell.
3. The method according to claim 2 wherein the cell is a breast, colon, renal, cervical, neuroblastomer, melanoma, pancreatic, prostate, or other type of solid tumor.