Heterocyclic kinase modulators

A compound having the structure of Formulas (I5), (I6), (I7) or (I8):

• wherein:
• L is
• E is independently a direct bond, O, C═O, S(O)u, or NR3;
• Y is CH2, CF2, O, C(O)—, OC(O)—, NR3, or S(O)u;
• q is an integer from 0 to 4;
• u is an integer from 0 to 2;
• R4, R5, and R6 are each independently hydrogen, halogen, nitro, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, perfluoroalkyl, substituted or unsubstituted alkylaminoalkyl, substituted or unsubstituted alkylaminocycloalkyl, substituted or unsubstituted alkylaminoalkylenecycloalkyl, substituted or unsubstituted alkylaminoheterocycloalkyl, substituted or unsubstituted aminocycloalkyl, substituted or unsubstituted aminoalkylenecycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted —O-aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted —O-heteroaryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocycloalkyl, substituted or unsubstituted heteroarylalkyl, —(CH2)jOR17, —(CH2)jC(O)R17, —(CH2)jC(O)OR17—(CH2)jNR18R19, (CH2)jC(O)NR18R19, —(CH2)jOC(O)NR18R19, —(CH2)jNR20C(O)R17, —(CH2)jNR20C(O)OR17, (CH2)jNR20C(O)NR18R19, (CH2)S(O)mR21, —(CH2)jNR20S(O)2R21, —(CH2)jS(O)2NR18R19;
• wherein each j is independently an integer from 0 to 6;
• and m is independently an integer from 0 to 2;
• R4 and R5 optionally form substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R1 and R2 are each independently hydrogen, halogen, nitro, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, perfluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted —O-aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted —O-heteroaryl, substituted or unsubstituted heteroarylalkyl, —(CH2)jOR12, —(CH2)jC(O)R12, —(CH2)jC(O)OR12, —(CH2)jNR13R14, —(CH2)jC(O)NR13R14, —(CH2)jOC(O)NR13R14, —(CH2)jNR15C(O)R12, —(CH2)jNR15C(O)OR12, —(CH2)jNR15C(O)NR13R14, —(CH2)jS(O)mR16, —(CH2)jS(O)2NR13R14, or —(CH2)jNR15S(O)2R16, wherein each j is independently an integer from 0 to 6, and m is independently an integer from 0 to 2;
• R3 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, perfluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroarylalkyl;
• B2 is:
• wherein:
• X1 is independently N or CR11;
• R10 is independently hydrogen, halogen, nitro, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, perfluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted —O-aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted —O-heteroaryl, substituted or unsubstituted heteroarylalkyl, —(CH2)jOR22, —(CH2)jC(O)R22, —(CH2)jC(O)OR22, —(CH2)jNR23R24, —(CH2)jC(O)NR23R24, —(CH2)jOC(O)NR23R24, —(CH2)jNR25C(O)R22, —(CH2)jNR25C(O)OR22, —(CH2)jNR25C(O)NR23R24, —(CH2)jS(O)mR26, —(CH2)jNR25S(O)2R26, —(CH2)jS(O)2NR23R24, wherein each j is independently an integer from 0 to 6;
• and m is independently an integer from 0 to 2;
• y is independently an integer from 0 to 4;
• R11 is independently a direct bond, hydrogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, perfluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, —(CH2)jOR22, —(CH2)jC(O)R22, —(CH2)jC(O)OR22, —(CH2)jNR23R24, —(CH2)jC(O)NR23R24, —(CH2)jOC(O)NR23R24, —(CH2)jNR25C(O)R22, —(CH2)NR25C(O)OR22, —(CH2)jNR25C(O)NR23R24, (CH2)jS(O)R26, —(CH2)jNR25S(O)2R26, —(CH2)jS(O)2NR23R24, wherein each j is independently an integer from 0 to 6;
• and m is independently an integer from 0 to 2;
• R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, and R26 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, perfluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted —O-aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted —O-heteroaryl, or substituted or unsubstituted heteroarylalkyl;
• or an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt, or solvate thereof.

A compound having the structure of Formulas (I9), (I10), (I11), (I12), (I13), (I14), or (I15):

• wherein:
• K is N or CR5;
• K2 is N or CR6;
• L is
• wherein:
• E is independently a direct bond, O, C═O, S(O)u, or NR3;
• Y is CH2, CF2, O, C(O)—, OC(O)—, NR3, or S(O)u;
• q is an integer from 0 to 4;
• u is an integer from 0 to 2;
• R4, R5, R6, R7, R8, and R9 are each independently hydrogen, halogen, nitro, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, perfluoroalkyl, substituted or unsubstituted alkylaminoalkyl, substituted or unsubstituted alkylaminocycloalkyl, substituted or unsubstituted alkylaminoalkylenecycloalkyl, substituted or unsubstituted alkylaminoheterocycloalkyl, substituted or unsubstituted aminocycloalkyl, substituted or unsubstituted aminoalkylenecycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted —O-aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted —O-heteroaryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocycloalkyl, substituted or unsubstituted heteroarylalkyl, —(CH2)jOR17, —(CH2)jC(O)R17, —(CH2)jC(O)OR17, —(CH2)jNR18R19, —(CH2)jC(O)NR18R19, —(CH2)jOC(O)NR18R19, —(CH2)jNR20C(O)R17, —(CH2)iNR20C(O)OR17, —(CH2)jNR20C(O)NR18R19, —(CH2)jS(O)mR21, —(CH2)jNR20S(O)2R21, —(CH2)jS(O)2NR18R19, wherein each j is independently an integer from 0 to 6;
• and m is independently an integer from 0 to 2;
• R4 and R5 optionally form substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or
• R4 and R7 optionally form substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or
• R7 and R8 optionally form substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R1 and R2 are each independently hydrogen, halogen, nitro, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, perfluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted —O-aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted —O-heteroaryl, substituted or unsubstituted heteroarylalkyl, —(CH2)jOR12, —(CH2)jC(O)R12, —(CH2)jC(O)OR12, —(CH2)jNR13R14, —(CH2)jC(O)NR13R14, —(CH2)jOC(O)NR13R14, —(CH2)jNR15C(O)R12, —(CH2)jNR15C(O)OR12, —(CH2)jNR15C(O)NR13R14, —(CH2)jS(O)mR16, —(CH2)jS(O)2NR13R14, or —(CH2)jNR15S(O)2R16, wherein each j is independently an integer from 0 to 6, and m is independently an integer from 0 to 2;
• R3 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, perfluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroarylalkyl;
• B is a substituted or unsubstituted heteroaryl selected from:
• wherein:
• X1 is independently N or C;
• and
• X2 is N(R11), O, or S;
• R10 is independently hydrogen, halogen, nitro, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, perfluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted —O-aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted —O-heteroaryl, substituted or unsubstituted heteroarylalkyl, —(CH2)jOR22, —(CH2)jC(O)R22, —(CH2)jC(O)OR22, —(CH2)jNR23R24, —(CH2)jC(O)NR23R24, —(CH2)jOC(O)NR23R24, —(CH2)jNR25C(O)R22, —(CH2)jNR25C(O)OR22, —(CH2)jNR25C(O)NR23R24, —(CH2)jS(O)mR26, (CH2)jNR25S(O)2 (O)2NR23R24 wherein each j is independently an integer from 0 to 6;
• and m is independently an integer from 0 to 2;
• y is independently an integer from 0 to 5;
• R11 is independently a direct bond, hydrogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, perfluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, —(CH2)jOR22, —(CH2)jC(O)R22, —(CH2)jC(O)OR22, —(CH2)jNR23R24, —(CH2)C(O)NR23R24, —(CH2)jOC(O)NR23R24, —(CH2)jNR25C(O)R22, —(CH2)jNR25C(O)OR22, —(CH2)jNR25C(O)NR23R24, —(CH2)jS(O)mR26, —(CH2)jNR25S(O)2R26, —(CH2)jS(O)2NR23R24, wherein each j is independently an integer from 0 to 6;
• and m is independently an integer from 0 to 2;
• R12, R17 and R22 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, perfluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted —O-aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted —O-heteroaryl, or substituted or unsubstituted heteroarylalkyl;
• R13, R14, R15, R16, R18, R19, R20, R21R23, R24, R25, and R26 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, perfluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted —O-aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted —O-heteroaryl, or substituted or unsubstituted heteroarylalkyl, or
• R13 and R14, R18 and R19, and R23 and R24 together with the N atom to which they are attached, each independently form substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl, or
• R12 and R15, R17 and R20, and R22 and R25 together with the N atom to which they are attached, each independently form substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl, or
• R13 and R15 or R14 and R15, R15 and R20 or R19 and R20, and R23 and R25 or R24 and R25 together with the N atom to which they are attached, each independently form substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl, or
• R15 and R16, R20 and R21, and R25 and R26 together with the N atom to which they are attached, each independently form substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
• wherein any of the R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, and R24 groups are each optionally independently substituted with 1 to 3 groups, each group independently selected from hydrogen, halogen, hydroxyl, amino, aminomonoalkyl, aminodialkyl, cyano, morpholine, nitro, difluoromethyl, trifluoromethyl, oxo, alkyl, —O-alkyl, and —S-alkyl;
• with the proviso that when the core structure of the compound having a structure of Formula (I14) is [1,2,4]triazolo-[4,3-b][1,2,4]triazine, then R10 is not hydrogen, halogen, nitro, cyano, hydroxyl, substituted or unsubstituted alkyl, perfluoroalkyl, —(CH2)jOR22, —(CH2)jC(O)R22, —(CH2)jC(O)OR22, —(CH2)jNR23R24, —(CH2)jS(O)mR26(CH2)jC(O)NR23R24, —(CH2)jS(O)2NR23R24;
• or when the core structure of the compound having a structure of Formula (I13) is [1,2,4]triazolo[4,3-a]pyrimidine then R10 is not H;
• or an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt, or solvate thereof.