Fused heterocyclic compounds useful as kinase modulators

1. A compound according to formula (III):

wherein

R 1 and R 2 are each independently hydrogen, —NR 7 R 8 or —C(═O)NR 7 R 8 ;

R 3 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, carbocyclyl, substituted carbocyclyl, heterocyclyl, substituted heterocyclyl, heteroaryl or substituted heteroaryl;

B is —C(═O)—, —NR 11 —, —C(═O)NR 11 —, or —NR 11 C(═O)—;

each R 5 is independently halogen, trifluoromethyl, cyano, hydroxy, nitro, C 1-6 alkyl, —C(═O)R 13 , —C(═O)NR 13 R 14 , —NR 13 R 14 , or —NR 13 C(═O)R 14 ;

each R 6 is independently halogen, trifluoromethyl, cyano, hydroxy, amino, substituted amino, nitro, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkylamino, or substituted alkylamino;

R 7 and R 8 are each independently hydrogen, alkyl, alkenyl, C 3-7 cycloalkyl, phenyl, benzyl, phenylethyl, naphthyl, a four to seven membered heterocyclo, or a five to six membered heteroaryl, or may join to form a heterocyclyl or heteroaryl;

R 11 is H;

R 13 and R 14 are each independently hydrogen, C 1-6 alkyl, substituted C 1-6 alkyl, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl or substituted heteroaryl, or R 13 and R 14 are taken together with the nitrogen to which they are both attached to form an optionally substituted monocyclic heterocyclyl, or an optionally substituted bicyclic heterocyclyl;

m is zero or an integer from 1 to 4; and

n is zero or an integer from 1 to 5.

2. The compound according to claim 1 , wherein

R 5 is —NR 13 R 14 or —C(═O)NR 13 R 14 ;

R 13 and R 14 are independently hydrogen, C 1-6 alkyl, or heterocyclyl optionally substituted with one to five R 12 ; or R 13 and R 14 are taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocyclyl optionally substituted with one to five R 12 ; and

R 12 is halogen, trifluoromethyl, cyano, hydroxy, nitro, C 1-6 alkyl, substituted C 1-6 alkyl, C 2-6 alkenyl, substituted C 2-6 alkenyl, C 2-6 alkynyl, substituted C 2-6 alkynyl, C 1-6 alkoxy, substituted C 1-6 alkoxy, carbocyclyl, substituted carbocyclyl, heterocyclyl, or substituted heterocyclyl.

3. The compound according to claim 2 , wherein R 5 is

v is zero or an integer from 1 to 2;

u is an integer from 1 to 2;

q is an integer from 1 to 2;

when (u+q) is 2 to 3, each W is independently CHR 9 ;

when (u+q) is 4, each W is independently O, S, CHR 9 , or NR 9 ;

each R 9 is independently hydrogen or C 1-6 alkyl optionally substituted with halogen, trifluoromethyl, cyano, or hydroxy;

R 12 is hydroxy or C 1-6 alkyl optionally substituted with halogen, trifluoromethyl, cyano, hydroxy, or nitro.

4. The compound according to claim 1 , wherein

R 3 is hydrogen, C 1-6 alkyl, or C 2-6 alkenyl, wherein said C 1-6 alkyl and C 2-6 alkenyl are optionally substituted with carbocyclyl, heterocyclyl, or heteroaryl.

5. The compound according to claim 1 , wherein

R 3 is a monocyclic 5- or 6-membered heterocyclyl or heteroaryl having from 1 to 4 heteroatoms selected from N, O, and S, or a bicyclic 8-, 9-, or 10-membered heterocyclic or heteroaryl having from 1 to 6 heteroatoms selected from N, O, and S, optionally substituted by one to three groups selected from halogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, nitro, cyano, —SO 3 H, —SR 16 , —S(═O) p R 16 , —S(═O) p NR 16 R 17 , —NR 16 S(═O) p R 17 , —OR 16 , —NR 16 R 17 , —NR 16 C(═O)R 17 , —NR 16 C(═O)NR 16 R 17 , —C(═O)OR 16 , —C(═O)R 16 , —OC(═O)R 16 , —C(═O)NR 16 R 17 , aryl, cycloalkyl, heterocyclyl, and heteroaryl;

R 16 and R 17 are each independently hydrogen or lower alkyl, or R 16 and R 17 are taken together with the nitrogen to which they are both attached to form an optionally substituted monocyclic heterocyclyl or heteroaryl, or an optionally substituted bicyclic heterocyclyl or heteroaryl; and

p is 1 or 2.

6. The compound according to claim 1 , wherein

R 3 is carbocyclyl optionally substituted by one to three groups selected from halogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, nitro, cyano, —SO 3 H, —SR 16 , —S(═O) p R 16 , —S(═O) p NR 16 R 17 , —NR 16 S(═O) p R 17 , —OR 16 , —NR 16 R 17 , —NR 16 C(═O)R 17 , —NR 16 C(═O)NR 16 R 17 , —C(═O)OR 16 , —C(═O)R 16 , —OC(═O)R 16 , —C(═O)NR 16 R 17 , aryl, cycloalkyl, heterocyclyl, and heteroaryl;

R 16 and R 17 are each independently hydrogen or lower alkyl, or R 16 and R 17 are taken together with the nitrogen to which they are both attached to form an optionally substituted monocyclic heterocyclyl or heteroaryl, or an optionally substituted bicyclic heterocyclyl or heteroaryl; and

p is 1 or 2.

7. The compound according to claim 1 , wherein

R 1 is hydrogen;

R 2 is hydrogen or —NR 7 R 8 ;

R 3 is hydrogen, C 1-4 alkyl substituted with phenyl, C 2-4 alkenyl substituted with phenyl, phenyl, heterocyclyl or heteroaryl, wherein said phenyl, heterocyclyl or heteroaryl is optionally substituted with one to three groups selected from

(i) C 1-4 alkyl;

(ii) substituted C 1-4 alkyl wherein the substituent is selected from halogen, hydroxy, amino, and oxo;

(iii) NR 16 R 17 wherein R 16 and R 17 are each independently hydrogen or lower alkyl, or R 16 , and R 17 are taken together with the nitrogen to which they are attached to form an optionally substituted saturated or unsaturated 5- to 6-membered heterocyclyl or heteroaryl;

(iv) aryl;

(v) substituted aryl wherein the substituent is selected from halogen, trifluoromethyl, cyano, hydroxy, amino, substituted amino, nitro, alkyl, substituted alkyl, alkoxy, and substituted alkoxy;

(vi) cycloalkyl;

(vii) substituted cycloalkyl wherein the substituent is selected from halogen, trifluoromethyl, cyano, hydroxy, amino, substituted amino, nitro, alkyl, substituted alkyl, alkoxy, and substituted alkoxy;

(viii) heterocyclyl or heteroaryl; and

(ix) substituted heterocyclyl or heteroaryl wherein the substituent is selected from halogen, trifluoromethyl, cyano, hydroxy, amino, substituted amino, nitro, alkyl, substituted alkyl, alkoxy, and substituted alkoxy;

R 5 is —NR 13 R 14 or —C(═O)NR 13 R 14 ;

R 6 is C 1-6 alkyl or substituted C 1-6 alkyl;

R 7 and R 8 are each independently hydrogen or C 1-4 alkyl;

each R 11 is independently hydrogen or lower alkyl;

R 13 and R 14 are each independently hydrogen, C 1-6 alkyl, or heterocyclyl optionally substituted with one to five R 12 ; or R 13 and R 14 are taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocyclyl optionally substituted with one to five R 12 ;

R 12 is halogen, trifluoromethyl, cyano, hydroxy, nitro, C 1-6 alkyl, substituted C 1-6 alkyl, C 2-6 alkenyl, substituted C 2-6 alkenyl, C 2-6 alkynyl, substituted C 2-6 alkynyl, C 1-6 alkoxy, substituted C 1-6 alkoxy, carbocyclyl, substituted carbocyclyl, heterocyclyl, or substituted heterocyclyl;

m is zero or 1; and

n is 1.

8. The compound according to claim 7 , wherein

R 2 is hydrogen or NH 2 ;

R 3 is phenyl optionally substituted with one to three groups selected from halogen, C 1-4 alkyl, C 2-4 alkenyl, C 1-4 haloalkyl, C 1-4 hydroxyalkyl, C 3-6 cycloalkyl optionally substituted with C 1-4 alkyl, heterocyclyl optionally substituted with C 1-4 alkyl, and NR 16 R 17 ;

R 5 is

wherein each W is independently O, S, CHR 9 , or NR 9 when (u+q) is 4; each W is independently CHR 9 when (u+q) is 2 to 3;

B is —C(═O)NH— or —NHC(═O)—;

R 6 is C 1-4 alkyl;

each R 9 is independently hydrogen or C 1-4 alkyl optionally substituted with hydroxy;

R 12 is halogen, hydroxy, or C 1-4 alkyl optionally substituted with halogen or hydroxy;

R 16 and R 17 are each independently hydrogen or C 1-4 alkyl; or R 16 and R 17 are taken together with the nitrogen to which they are both attached to form an optionally substituted 5- to 6-membered heterocyclyl;

u is an integer from 1 to 2; and

q is an integer from 1 to 2.

9. A pharmaceutical composition comprising one or more compounds according to claim 1 and a pharmaceutically acceptable carrier or diluent.

10. The compound according to claim 1 wherein:

R 1 is H;

R 2 is H or NH 2 ; and

R 5 is

m is 0 or 1; and

n is 1.

11. The compound according to claim 1 wherein in the compound according to formula (III),

R 1 is H;

R 2 is H or NH 2 ;

the group having the structure

is:

and n is 1.