| 主权项 |
1. A method of inhibiting proliferation of a cancer cell, comprising contacting the cancer cell with an effective amount of a 2,4-pyrimidinediamine compound according to structural formula (I): or a salt or N-oxide thereof, wherein:
L1 and L2 are each, independently of one another, selected from a lower alkyldiyl linker, a lower alkylene linker and a covalent bond;R2 is selected from the group consisting of lower alkyl optionally substituted with an Rb group,where Y is NH, O or CH2;
R2′ is hydrogen, methyl or lower alkyl; R4′ is hydrogen, methyl or lower alkyl; R4 iswhere Z1 is N and Z2 is O;
R5 is selected from the group consisting of chloro, iodo, bromo, fluoro and —CF3; R6 is hydrogen; each R8 is independently selected from the group consisting of hydrogen, lower alkyl, —(CH2)n—OH, —ORa, —(CH2)n—NRcRc, —O(CH2)n—Ra, —O(CH2)n—Rb, —C(O)ORa, —C(S)ORa, halo, —CF3 and —OCF3; each R9 is independently selected from the group consisting of hydrogen, lower alkyl, —ORa, —(CH2)n—NRcRc, —O(CH2)n—Ra, —O(CH2)n—Rb, —C(O)—NRcRc, —C(S)—NRcRc, —S(O)2—NR′Rc, —NHC(O)Ra, —NHC(S)Ra, —C(O)—NH—(CH2)n—NRcRc, —C(S)—NH—(CH2)n—NRcRc, halo, —CF3, —OCF3, each R10 is independently selected from the group consisting of hydrogen, lower alkyl, —(CH2)n—OH, —(CH2)n—NRcRc, —ORa, —O(CH2)n—Ra, —O(CH2)n—Rb, halo, —CF3, —OCF3, each R11 is independently selected from the group consisting of —ORa, —NRcRc and —NRaRd; each R12 is independently selected from the group consisting of lower alkyl, arylalkyl, —ORa, —NRcRc, —C(O)Ra, —C(O)ORa and —C(O)NRcRc; each R13 is independently selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, —C(O)NRcRc and —C(O)NH2; each R15 is independently selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl and phenyl; each R16 is independently selected from the group consisting of hydrogen, methyl, lower alkyl, lower cycloalkyl, lower branched alkyl and lower cycloalkylmethyl; each R17 is independently selected from the group consisting of hydrogen, lower alkyl, and Rd; each R18 is independently selected from the group consisting of hydrogen, and lower alkyl; each R19 is independently selected form the group consisting of hydrogen, lower alkyl, and Rd; each R20 is independently selected from the group consisting of hydrogen, lower alkyl, and Rd; each m is independently an integer from 1 to 3; each n is independently an integer from 1 to 3; each Ra is independently selected from the group consisting of hydrogen, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, phenyl and benzyl; each Rb is independently selected from the group consisting of −ORa, —CF3, —OCF3, —NRcRc, —C(O)Ra, —C(S)Ra, —C(O)ORa, —C(S)ORa, —C(O)NRcRc, —C(S)NRcRc, —S(O)2NRcRc, —C(O)NRaRd, —C(S)NRaRd and —S(O)2NRaRd; each Rc is independently selected from the group consisting of hydrogen, lower alkyl and lower cycloalkyl, or, alternatively, two Rcs may be taken together with the nitrogen atom to which they are bonded to form a 5-7 membered saturated ring which optionally includes 1-2 additional heteroatomic groups selected from O, NRa, NRa—C(O)Ra, NRa—C(O)ORa and NRa—C(O)NRa; and each Rd is independently selected from lower mono-hydroxyalkyl and lower di-hydroxyalkyl. |
