Bi-aryl meta-pyrimidine inhibitors of kinases

A compound having the structure (A):

• wherein:
• X is selected from a group consisting of a bond, O, C═O, SO2, and CH2;
• Y is selected from a group consisting of a bond or NR9;
• or X and Y taken together is a bond;
• each of R1 and R2 is independently selected from a group consisting of H, C1-C6 substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• or R1 and R2 taken together is a bond;
• or R1 and R2 taken together form a moiety selected from a group consisting of (CH2)m, (CH2)r—S—(CH2)m, (CH2)r—SO—CH2)m, (CH2)r—SO2—(CH2)m, (CH2)r—NR9—CH2)m, and (CH2)r—O—CH2)m;
• each of p, q, r, n, m is independently an integer having the value between 0 and 6,
• R9 is selected from a group consisting of H, C1-C6 alkyl, C1-C6 cycloalkyl, C1-C6 branched alkyl, C1-C6 substituted alkyl, C1-C6 aminoalkyl, and C1-C6 hydroxyalkyl;
• G0 is selected from a group consisting of N, O, H, and CH,
• with the proviso that if G0 is N, then:
• each of R3 and R4 is independently selected from a group consisting of H, C1-C6 alkyl, C1-C6 substituted or unsubstituted hydroxyalkyl or aminoalkyl, C1-C6 substituted or unsubstituted branched alkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, or R3 and R4 taken together form a moiety selected from a group consisting of (CH2)m, (CH2)r—S—(CH2)m, (CH2)r—SO—(CH2)m, (CH2)r—SO2—(CH2)m, (CH2)r—NR9—(CH2)m, and (CH2)r—O—(CH2)m;
• with the additional proviso that if G0 is N, then:
• R1 and R9 taken together form a moiety selected from a group consisting of (CH2)m, (CH2)r—S—CH2)m, (CH2)r—SO—CH2)m, CH2)r—SO2—(CH2)m, (CH2)r—NR9—(CH2)m, and (CH2)r—O—(CH2)m;
• or R1 and R4 taken together forms a moiety selected from a group consisting of (CH2)m, (CH2)r—S—(CH2)m, (CH2)r—SO—CH2)m, (CH2)r—SO2—(CH2)m, (CH2)r—NR9—(CH2)m, and (CH2)r—O(CH2)m;
• or R9 and R4 taken together form a moiety selected from a group consisting of (CH2)m, (CH2)r—S—(CH2)m, (CH2)r—SO—(CH2)m, (CH2)r—SO2—(CH2)m, (CH2)r—NR9—(CH2)m, and (CH2)r—O—(CH2)m;
• or R3 and R4 taken together form a moiety selected from a group consisting of (CH2)m, (CH2)r—S—CH2)m, (CH2)r—SO—(CH2)m, (CH2)r—SO2—(CH2)m, (CH2)r—NR6—(CH2)m, and (CH2)r—O—(CH2)m;
• with the further proviso that if G0 is O, then:
• R3 is selected from a group consisting of H, C1-C6 alkyl and C1-C6 substituted or unsubstituted hydroxyalkyl or aminoalkyl, substituted or unsubstituted branched alkyl, substituted or unsubstituted cycloalkyl, substituted heterocyclic connected through carbon or nitrogen, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl connected through carbon or nitrogen, with no group R4;
• R1 and R9 taken together form a moiety selected from a group consisting of (CH2)m, (CH2)r—S—(CH2)m, (CH2)r—SO—(CH2)m, (CH2)r—SO2—(CH2)m, (CH2)r—NR9—(CH2)m, and (CH2)r—O(CH2)m;
• or R1 and R3 taken together form a moiety selected from a group consisting of (CH2)m, (CH2)r—S—(CH2)m, (CH2)r—SO—CH2)m, (CH2)r—SO2—(CH2)m, (CH2)r—NR9—(CH2)m, and (CH2)r—O(CH2)m;
• or R9 and R3 taken together form a moiety selected from a group consisting of (CH2)m, (CH2)r—S—CH2)m, (CH2)r—SO—CH2)m, (CH2)r—SO2—(CH2)m, (CH2)r—NR9—(CH2)m, and (CH2)r—O—(CH2)m;
• with the further proviso that if G0=CH, then each of R3 and R4 is independently selected from a group consisting of H, C1-C6 alkyl, C1-C6 substituted or unsubstituted hydroxyalkyl or aminoalkyl, C1-C6 substituted or unsubstituted branched alkyl, substituted or unsubstituted aryl, C1-C6 substituted or unsubstituted heterocycle connected through carbon or nitrogen, and substituted or unsubstituted heteroaryl connected through carbon or nitrogen, or R3 and R4 taken together form a moiety selected from a group consisting of (CHR9)r—(CHR9)m—(CHR9)p, (CHR9)r—S—CHR9)m, (CHR9)r—SO(CHR9)m, (CHR9)r—SO2—(CHR9)m, (CHR9)r—NR9—CHR9)m, and (CHR9)r—O(CHR9)m;
• G is N or CR6, and each G is independent of each other G, with the further proviso that not more than two groups G can be N, with the further proviso that for each CR6, each R6 is independent of each other group R6.
• R5 is methyl;
• wherein each of R6, R7, R8 is independently selected from a group consisting of H, C1-C6 substituted or unsubstituted alkyl, C1-C6 substituted or unsubstituted alkenyl, C1-C6 substituted or unsubstituted alkynyl, C1-C6 substituted or unsubstituted hydroxyalkyl or aminoalkyl, C1-C6 substituted or unsubstituted branched alkyl, C1-C6 substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl connected through carbon or a heteroatom, substituted or unsubstituted heteroaryl connected through carbon or a heteroatom, C1-C6 alkoxy, a halogen, CF3, —OCF3, CHR3R4, SR3, SOR3, SO2R3, SO2NR3R4, SO3R3, POR3, PO2R3, PO2NR3R4, PO2CR3R4, PO3R3, NR3R4, NO2, CN, OH, CONR3R4, COR3, COOR3, NR3COR4, NR3CONR3R4, OCONR3R4, CSNR3R4, CSR3, NR3CSNR3R4, SCONR3R4, SCSNR3R4, and SCSNR3R4;
• or any of R6 and R7 taken together, or R7 and R8 taken together, or R6 and R8 taken together form a moeity independently selected from a group consisting of —HN—CH═CH—, —HN—N═CH—, —HN—N═N—, —O(CH2)nO—, —S(CH2)nS—, —N═CH—S—, —CH═N—O—, —CH═N—S—, —N═CH—O—, —C═N—O—, —C═N—O—, —CH═CH—CH═CH—, —N═CH—CH═CH—, —CH═N—CH═CH—, CH═CH, and —S—CH═CH—;
• or R3 and R4 taken together form a moiety selected from a group consisting of (CHR9)r—(CHR9)m—(CHR9)p, (CHR9)r—S—CHR9)m, (CHR9)r—SO—(CHR9)m, (CHR9)r—SO2—CHR9)m, (CHR9)r—NR9—CHR9)m, and (CHR9), —O—CHR9)m;
• A is selected from a group consisting of O, NR3, CR3R4, S, SO, and SO2;
• G1 is selected from a group consisting of CH, N, NH, S, and O;
• G2 is selected from a group consisting of CR7, N, NH, S, and O, with each group R7 being independent of every other group R7;
• and if G1 or G2 is NH, S, or O, then Q is a five membered heteroaromatic ring, optionally fused to a six member aromatic or non-aromatic ring;
• and if G1 or G2 is N, then Q is a five or a six membered aromatic ring, optionally fused to a six member aromatic or non-aromatic ring;
• with the further proviso that X or G0 includes at least one heteroatom included with X and selected from O, S and N, or G0 comprises at least four non-hydrogen atoms, inclusive of the heteroatom, and R3 and R4, or R1 and R9, or R1 and R4, or R9 and R4 taken together form an aromatic, heteroaromatic, cyclic or heterocyclic ring system, or if a noncyclic system is present, then more than one heteroatom is present, and if A is NR3, then any of R6, R7 or R8, or any combination thereof independently includes at least two non-hydrogen substitutents, or if A is NR3, then Q forms a fused ring from R6 to R7, or from R7 to R8,
• or pharmaceutically acceptable salts, hydrates, solvates, crystal forms, N-oxides, and individual diastereomers of the compound (A).