Phosphorus Derivatives as Kinase Inhibitors

A compound of the Formula VIa:

• wherein
• X1 is NRb1 or CRb;
• X3 is NRd1 or CRd;
• X4 is NRe1 or CRe;
• Ring A and Ring E are each an independently selected aryl or heteroaryl ring, the heteroaryl ring being a 5- or 6-membered ring containing 1 to 4 heteroatoms selected from N, O and S(O)r;
• each Ra, Rb, Rd, Re, and Rg is independently halo, —CN, —NO2, —R1, —OR2, —O—NR1R2, —NR1R2, —NR1—NR1R2, —NR1—OR2, —C(O)YR2, —OC(O)YR2, —NR1C(O)YR2, —SC(O)YR2, —NR1C(═S)YR2, —OC(═S)YR2, —C(═S)YR2, —YC(═NR1)YR2, —YC(═N—OR1)YR2, —YC(═N—NR1R2)YR2, —YP(═O)(YR3)(YR3), —Si(R3d)3, —NR1SO2R2, —S(O)rR2, —SO2NR1R2 or —NR1SO2NR1R2;
• or alternatively, each Ra and Rg independently is or includes —P(═O)(R3)2 or a ring system containing the moiety —P(═O)(R3)— as a ring member;
• and Rb1, Rd1 and Re1 are absent;
• or alternatively two adjacent substituents selected from Rd, Rd1, Re, and Re1, or two adjacent Ra moieties, form, with the atoms to which they are attached, a fused, 5-, 6- or 7-membered saturated, partially saturated or unsaturated ring, which contains 0-4 heteroatoms selected from N, O and S(O)r and which may bear up to four substituents;
• at least one of Ra and Rg is or contains —P(═O)(R3)2;
• L is O or NH;
• r is 0, 1 or 2;
• s is 1, 2, 3, 4 or 5;
• p is 1, 2, 3 or 4;
• each Y is independently a bond, —O—, —S— or —NR1—;
• each R1 and R2 is independently H or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic or heteroaryl moiety;
• each R3 is independently an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic or heteroaryl moiety, or two adjacent R3 moieties combine to form a ring system including a phosphorous atom;
• each R3a is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic, and heteroaryl;
• alternatively, each NR1R2 moiety may be a 5-, 6- or 7-membered saturated, partially saturated or unsaturated ring, which can be optionally substituted and which contains 0-2 additional heteroatoms selected from N, O and S(O)r;
• and,
• each of the foregoing alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocyclic moieties is optionally substituted;
• wherein:
• (a) each non-cyclic alkyl group contains 1-6 carbon atoms, each non-cyclic alkenyl or alkynyl group contains 2-8 carbon atoms, each cycloalkyl and cycloalkenyl group contains 3-13 carbon atoms, each cycloalkynyl group contains 8-13 carbon atoms, and each heteroalkyl group is a branched or unbracnhed alkyl, alkenyl or alkynyl group of up to 7 carbon atoms in addition to 1-4 heteroatoms independently selected from N, O, S and P;
• (b) each heterocycle is a non-aromatic ring or ring system having five to fourteen ring atoms of which one or more, preferably one to four, is each a heteroatom independently selected from N, O, S or P, and the remainder of ring atoms are carbon;
• (c) each aryl group is an aromatic carbocyclic ring or ring system containing 6-14 ring atoms;
• and (d) each heteroaryl moiety is an aromatic ring or ring system having five to fourteen ring atoms of which one or more, often one to four, is each a heteroatom independently selected from N, O, S or P, and the remainder of ring atoms are carbon.