Inhibition of RAF kinase using aryl and heteroaryl substituted heterocyclic ureas

1. A method for treating colon cancer comprising administering an effective amount of a compound of formula I, including pharmaceutically acceptable salts thereof, to a host in need thereof:

wherein A is

wherein R1 is C 3 -C10 alkyl, C3-C 10 cycloalkyl, up to per-halosubstituted C 1 -C 10 alkyl or up to per-halosubstituted C 3 -C 10 cycloalkyl;

B is phenyl substituted by one or more substituents which are independently halogen, up to per-halosubstitution, or X n ,

wherein n is 0-3 and each X is independently —CN, CO 2 R 5 , —C(O)NR 5 R 5′ , —C(O)R 5 , —NO 2 , —OR 5 , —SR 5 , —NR 5 R 5′ , —NR 5 C(O)OR 5′ , —NR 5 C(O)R 5′ , C 1 -C 10 alkyl, C 2-10 -alkenyl, C 1-10 -alkoxy, C 3 -C 10 cycloalkyl, C 6 -C 14 aryl, C 7 -C 24 alkaryl, C 3 -C 13 heteroaryl, C 4 -C 23 alkheteroaryl, substituted C 1 -C 10 alkyl, substituted C 2-10 -alkenyl, substituted C 1-10 -alkoxy, substituted C 3 -C 10 cycloalkyl, substituted C 4 -C 23 alkheteroaryl or —Y—Ar;

where X is a substituted group, it is substituted by one or more substituents which are independently —CN, —CO 2 R 5 , —C(O)R 5 , —C(O)NR 5 R 5′ , —OR 5 , —SR 5 , —NR 5 R 5′ , —NO 2 , —NR 5 C(O)R 5′ , —NR 5 C(O)OR 5′ or halogen up to per-halosubstitution;

wherein R 5 and R 5′ are independently H, C 1 -C 10 alkyl, C 2 -10 -alkenyl, C 3 -C 10 cycloalkyl, C 6 -C 14 aryl, C 3 -C 13 heteroaryl, C 7 -C 24 alkaryl, C 4 -C 23 alkheteroaryl, up to per-halosubstituted C 1 -C 10 alkyl, up to per-halosubstituted C 2-10 -alkenyl , up to per-halosubstituted C 3 -C 10 cycloalkyl, up to per-halosubstituted C 6 -C 14 aryl or up to per-halosubstituted C 3 -C 13 heteroaryl,

wherein Y is —O—, —S—, or —(CH 2 )— m

m=1-3, and

Ar is phenyl or pyridinyl which is optionally substituted by halogen up to per-halosubstitution and optionally substituted by Z n1 , wherein n1 is 0 to 3 and each Z is independently —CN, —C(O)R 5 , —CO 2 R 5 , —C(O)NR 5 R 5′ , —C(O)NR 5 , —NO 2 , —OR 5 , —SR 5 , —NR 5 R 5′ , —NR 5 C(O)OR 5′ , —NR 5 C(O)R 5′ , C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C6-C14 aryl, C 3 -C 13 heteroaryl, C 7 -C 24 alkaryl, C4-C 23 alkheteroaryl, substituted C 1 -C 10 alkyl, substituted C 3 -C 10 cycloalkyl, substituted C 7 -C 24 alkaryl or substituted C 4 -C 23 alkheteroaryl;

wherein if Z is a substituted group, it is substituted by the one or more substituents which is independently —CN, —CO 2 R 5 , —C(O)NR 5 R 5′ , —OR 5 , —SR 5 , —NO 2 , —NR 5 R 5′ , —NR 5 C(O)R 5′ or —NR 5 C(O)OR 5′ ,

wherein R 2 is heteroaryl, substituted phenyl, unsubstituted phenyl, substituted pyridinyl or unsubstituted pyridinyl,

wherein if R 2 is a substituted group, it is substituted by one or more substituents which is halogen, up to per-halosubstitution, or V n ,

wherein n=0-3 and each V is —CN, —CO 2 R 5 , —C(O)NR 5 R 5′ , —OR 5 , —SR 5 , —NR 5 R 5′ , —OC(O)NR 5 R 5′ , —NR 5 C(O)OR 5′ , —NR 5 C(O)OR 5′ , —SO 2 R 5 , —SOR 5 , —NR 5 C(O)R 5′ , —NO 2, , C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 6 -C 14 aryl, C 3 -C 13 heteroaryl, C 7 -C 24 alkaryl, C 4 -C 24 alkheteroaryl, substituted C 1 -C 10 alkyl, substituted C 3 -C 10 cycloalkyl, substituted C 6 -C 14 aryl, substituted C 3 -C 13 heteroaryl, substituted C 7 -C 24 alkaryl or substituted C 4 -C 24 alkheteroaryl,

where V is a substituted group, it is substituted by one or more substituents which are independently halogen, up to per-halosubstitution, —CN, —CO 2 R 5 , —C(O)R 5 , —C(O)NR 5 R 5 , —NR 5 R 5′ , —OR 5 , —SR 5 , —NR 5 C(O)R 5′ , —NR 5 C(O)OR 5′ or —NO 2 ,

wherein R 5 and R 5′ are each independently as defined above.