PHOSPHOROUS DERIVATIVES AS KINASE INHIBITORS

1 . A compound of the formula VIa:

wherein

X 1 is NR b1 or CR b ;

X 3 is NR d1 or CR d ;

X 4 is NR e1 or CR e ;

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 occurrence of R a , R b , R d , R e , and R g is independently selected from the group consisting of halo, —CN, —NO 2 , —R 1 , —OR 2 , —O—NR 1 R 2 , —NR 1 R 2 , —NR 1 —NR 1 R 2 , —NR 1 —OR 2 , —C(O)YR 2 , —OC(O)YR 2 , —NR 1 C(O)YR 2 , —SC(O)YR 2 , —NR 1 C(═S)YR 2 , —OC(═S)YR 2 , —C(═S)YR 2 , —YC(═NR 1 )YR 2 , —YC(═N—OR 1 )YR 2 , —YC(═N—NR 1 R 2 )YR 2 , —YP(═O)(YR 3 )(YR 3 ), —Si(R 3a ) 3 , —NR 1 SO 2 R 2 , —S(O) r R 2 , —SO 2 NR 1 R 2 and —NR 1 SO 2 NR 1 R 2 ; or alternatively, each R a and R g may also be an independently selected moiety, —P(═O)(R 3 ) 2 or a ring system containing the moiety —P(═O)(R 3 )— as a ring member;

R b1 , R d1 and R e1 are absent;

or alternatively two adjacent substituents selected from R d , R d1 , R e , and R e1 , or two adjacent R a moieties, can 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 R a and R g is or contains a moiety, —P(═O)(R 3 ) 2 or a ring system containing the moiety —P(═O)(R 3 )— as a ring member;

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 occurrence of Y is independently a bond, —O—, —S— or —NR 1 —;

each occurrence of R 1 and R 2 is independently H or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic or heteroaryl moiety;

each occurrence of R 3 is independently an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic or heteroaryl moiety, or two adjacent R 3 moieties combine to form a ring system including a phosphorous atom;

each occurrence of R 3a is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic, and heteroaryl;

alternatively, each NR 1 R 2 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.

2 - 22 . (canceled)

23 . A method for treating cancer in a subject, said method comprising administering to said subject a therapeutically effective amount of a compound of formula VIa:

wherein

X 1 is NR b1 or CR b ;

X 3 is NR d1 or CR d ;

X 4 is NR e1 or CR e ;

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 occurrence of R a , R b , R d , R e , and R g is independently selected from the group consisting of halo, —CN, —NO 2 , —R 1 , —OR 2 , —O—NR 1 R 2 , —NR 1 R 2 , —NR 1 —NR 1 R 2 , —NR 1 —OR 2 , —C(O)YR 2 , —OC(O)YR 2 , —NR 1 C(O)YR 2 , —SC(O)YR 2 , —NR 1 C(═S)YR 2 , —OC(═S)YR 2 , —C(═S)YR 2 , —YC(═NR 1 )YR 2 , —YC(═N—OR 1 )YR 2 , —YC(═N—NR 1 R 2 )YR 2 , —YP(═O)(YR 3 )(YR 3 ), —Si(R 3a ) 3 , —NR 1 SO 2 R 2 , —S(O) r R 2 , —SO 2 NR 1 R 2 and —NR 1 SO 2 NR 1 R 2 ; or alternatively, each R a and R g may also be an independently selected moiety, —P(═O)(R 3 ) 2 or a ring system containing the moiety —P(═O)(R 3 )— as a ring member;

R b1 , R d1 and R e1 are absent;

or alternatively two adjacent substituents selected from R d , R d1 , R e , and R e1 , or two adjacent R a moieties, can 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 R a and R g is or contains a moiety, —P(═O)(R 3 ) 2 or a ring system containing the moiety —P(═O)(R 3 )— as a ring member;

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 occurrence of Y is independently a bond, —O—, —S— or —NR 1 —;

each occurrence of R 1 and R 2 is independently H or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic or heteroaryl moiety;

each occurrence of R 3 is independently an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic or heteroaryl moiety, or two adjacent R 3 moieties combine to form a ring system including a phosphorous atom;

each occurrence of R 3a is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic, and heteroaryl;

alternatively, each NR 1 R 2 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.

24 . A method for making the compound

wherein the method comprises reacting the compound

with the compound

25 . The method of claim 24 , wherein the compound

is formed by a method comprising reacting the compound

with the compound

26 . The method of claim 25 , wherein the compound

is formed by a method comprising reacting the compound

with the compound

27 . A compound, which is

28 . A compound, which is