CPC C07D 495/04 (2013.01) [A61K 38/1709 (2013.01); C07C 235/20 (2013.01); C07C 317/08 (2013.01); C07D 207/14 (2013.01); C07D 211/58 (2013.01); C07D 211/62 (2013.01); C07D 231/40 (2013.01); C07D 295/185 (2013.01); C07D 295/26 (2013.01); C07D 401/04 (2013.01); C07D 401/06 (2013.01); C07D 401/12 (2013.01); C07D 405/12 (2013.01); C07D 409/04 (2013.01); C07D 413/12 (2013.01); C07D 417/12 (2013.01); C07D 471/10 (2013.01); C07D 487/04 (2013.01); C07D 487/10 (2013.01); C12N 9/14 (2013.01); C12Q 1/6886 (2013.01); C12Q 2600/156 (2013.01); C12Q 2600/158 (2013.01); C12Y 306/05002 (2013.01); G01N 2500/04 (2013.01)] | 30 Claims |
1. A human K-Ras protein having a cysteine at residue 12, wherein said cysteine is covalently bonded to a compound, wherein said compound has the formula
R1-L1-L2-L3-E,
wherein
R1 is substituted or unsubstituted fused ring aryl or substituted or unsubstituted fused ring heteroaryl;
L1 is substituted or unsubstituted heteroarylene;
L2 is a bond;
L3 is
wherein
f8 is an integer from 0 to 8;
each R2C is independently oxo, halogen, —CXc3, —CN, —SO2Cl, —SOn3R10c, —SOv3NR7cR8c, —NHNH2, —ONR7cR8c, —NHC═(O)NHNH2, —NHC═(O)NR7R8c, —N(O)m3, —NR7cR8c, —C(O)R9c, —C(O)—OR9c, —C(O)NR7cR8c, —OR10c, —NR7cSO2R10c, —NR7cC═(O)R9c, —NR7cC(O)—OR9c, —NR7cOR9c, —OCXc3, —OCHXc2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; wherein two adjacent R2C substituents are optionally joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
each R7c, R8c, R9c and R10c is independently hydrogen, halogen, —CF3, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2Cl, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC═(O)NHNH2, —NHC═(O)NH2, —NHSO2H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCF3, —OCHF2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R7c and R8c are optionally joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
m3 and v3 are independently an integer from 1 to 2;
n3 is independently an integer from 0 to 4;
Xc is independently —Cl, —Br, —I, or —F; and,
prior to covalently bonding to the cysteine 12,
E is,
wherein R13 is hydrogen, halogen, —CXb3, —CN, —SO2Cl, —SOrR17, —SOpNR14R15, —NHNH2, —ONR14R15, —NHC═(O)NHNH2, —NHC(O)NR14R15, —N(O)q, —NR14R15, —C(O)R16, —C(O)—OR16, —C(O)NR14R15, —OR17, —NR14SO2R17, —NR14C═(O)R16, —NR14C(O)—R16, —NR14OR16, —OCXb3, —OCHXb2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
wherein R14, R15, R16, and R17 are independently hydrogen, halogen, —CF3, —CN, —OH, —NH2, —COH, —CONH2, —NO2, —SH, —SO2Cl, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC═(O)NHNH2, —NHC═(O)NH2, —NHSO2H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCF3, —OCHF2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
wherein R14 and R15 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
wherein p is 1 or 2;
wherein q is an integer from 1 to 2;
wherein r is an integer from 0 to 4;
wherein Xb is independently Cl, Br, I, or F; and
wherein each substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted heteroaryl, and substituted aryl is independently substituted with a substituent group.
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