Oxygen linked pyrimidine derivatives

A method of treating a condition in a mammal in which inhibition of one or more protein kinase(s) inhibits a pathology or a symptomology of the condition, the method comprising administration of a therapeutically effective amount of a compound of the formula (I)

• wherein:
• R1 and R2 are each independently selected from the group consisting of:
• H, halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, cycloalkylheteroalkyl, heterocycloalkylheteroalkyl, heteroarylheteroalkyl, arylheteroalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxyaryl, alkenyloxy, alkynyloxy, cycloalkylkoxy, heterocycloalkyloxy, aryloxy, arylalkyloxy, phenoxy, benzyloxy, heteroaryloxy, amino, alkylamino, aminoalkyl, acylamino, arylamino, sulfonylamino, sulfinylamino, —COOH, —COR3, —COOR3, —CONHR3, —NHCOR3, —NHCOOR3, —NHCONHR3, alkoxycarbonyl, alkylaminocarbonyl, alkylsulfonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, aminosulfonyl, —SR3, R4S(O)R6—, R4S(O)2R6—, R4C(O)N(R5)R6—, R4SO2N(R5)R6—, R4N(R5)C(O)R6—, R4N(R5)SO2R6—, R4N(R5)C(O)N(R5)R6— and acyl, each of which may be optionally substituted;
• each R3, R4, and R5 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which may be optionally substituted;
• each R6 is independently selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which can be optionally substituted;
• Z2 is selected from the group consisting of a bond, O, S, —N(R7)—, —N(R7)C1-2alkyl-, and —C1-2alkylN(R7)—;
• each R7 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which can be optionally substituted;
• Ar1 and Ar2 are independently selected from the group consisting of aryl and heteroaryl, each of which may be optionally substituted, with the proviso that Ar1 and Ar2 are not both phenylene;
• L is a group of formula:
• —X1—Y—X2—
• wherein X1 is attached to Ar1 and X2 is attached to Ar2, and wherein X1, X2 and Y are selected such that the group L has between 5 and 15 atoms in the normal chain,
• X1 and X2 are each independently a heteroalkyl group containing at least one oxygen atom in the normal chain,
• Y is a group of formula —CRa═CRb— or an optionally substituted cycloalkyl group,
• wherein Ra and Rb are each independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which may be optionally substituted, or
• Ra and Rb are joined such that when taken together with the carbon atoms to which they are attached they form a cycloalkenyl or cycloheteroalkenyl group;
• or a pharmaceutically acceptable salt or N-oxide thereof;
• wherein the condition is selected from the group consisting of myelofibrosis, acute myeloid leukemia, and colon cancer.