HYDROXYSULFONYLALKYLENE-, PHOSPHONOALKYLENE- OR DIFLUORO(PHOSPHONONON)METHYL- SUBSTITUTED BENZENE, OR BENZOFURAN DERIVATIVES AS NON-PEPTIDIC CDC25 INHIBITORS

摘要

The present application relates to compounds of the fornula (VII), wherein the substituents R<1>-R<5>, X and Y are as defined in the description and to compounds of formula (VIII) or formula (IX) and when R<3> is in the ortho position to X, R<3> and R<4> are taken together with the atoms to which are each attached to form an aromatic heterocyclic ring. The application further relates to polypeptides which comprise the ligand binding domain of Cdc25, crystalline forms of these polypeptides and the use of these crystalline forms to determine the three dimensional structure of the catalytic domain of Cdc25. The invention also relates to the use of the three dimensional structure of the Cdc25 catalytic domain in methods of designing and/or identifying potential inhibitors of Cdc25 activity, for example, compounds which inhibit the binding of a native substrate to the Cdc25 catalytic domain.