Indazole, benzisoxazole, and benzisothiazole kinase inhibitors

1. A compound of formula (I)

or a therapeutically acceptable salt thereof, wherein

A is phenyl;

X is S;

R 1 and R 2 are independently selected from the group consisting of hydrogen, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkyl, aryl, arylalkyl, aryloxy, aryloxyalkyl, halo, haloalkoxy, haloalkyl, heterocyclyl, heterocyclylalkenyl, heterocyclylalkoxy, heterocyclylalkyl, heterocyclyloxyalkyl, hydroxy, hydroxyalkoxy, hydroxyalkyl, (NR a R b )alkoxy, (NR a R b )alkenyl, (NR a R b )alkyl, (NR a R b )alkynyl, (NR a R b )carbonylalkenyl, and (NR a R b )carbonylalkyl;

R 3 and R 4 are each independently selected from the group consisting of hydrogen, alkoxy, alkoxyalkoxy, alkyl, halo, haloalkoxy, haloalkyl, and hydroxy;

R 5 is LR 6 ;

L is selected from the group consisting of (CH 2 ) m N(R 7 )C(O)N(R 8 )(CH 2 ) n and CH 2 C(O)NR 7 , wherein m is 0 and n is 0, and wherein each group is drawn with its left end attached to A;

R 6 is selected from the group consisting of hydrogen, aryl, cycloalkyl, heterocyclyl, and 1,3-benzodioxolyl wherein the 1,3-benzodioxolyl can be optionally substituted with one, two, or three substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, aryl, arylalkoxy, arylalkyl, aryloxy, carboxy, cyano, cycloalkyl, halo, haloalkoxy, haloalkyl, a second heterocyclyl group, heterocyclylalkyl, hydroxy, hydroxyalkyl, nitro, —NR c R d , and (NR c R d )alkyl;

R 7 and R 8 are independently selected from the group consisting of hydrogen and alkyl;

R 9 is selected from the group consisting of hydrogen, alkenyl, alkoxyalkyl, alkyl, alkylcarbonyl, aryl, heterocyclylalkyl, hydroxyalkyl, and (NR a R b )alkyl;

R a and R b are independently selected from the group consisting of hydrogen, alkenyl, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylalkyl, arylcarbonyl, arylsulfonyl, haloalkylsulfonyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, and heterocyclylsulfonyl; and

R c and R d are independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclylalkyl and heterocyclyl.

2. The compound of claim 1 of formula (II)

or a therapeutically acceptable salt thereof, wherein

X is S;

R 1 and R 2 are independently selected from the group consisting of hydrogen, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkyl, aryloxy, aryloxyalkyl, halo, haloalkoxy, haloalkyl, heterocyclyl, heterocyclylalkenyl, heterocyclylalkoxy, heterocyclylalkyl, heterocyclyloxyalkyl, hydroxy, hydroxyalkoxy, hydroxyalkyl, (NR a R b )alkoxy, (NR a R b )alkenyl, (NR a R b )alkyl, (NR a R b )carbonylalkenyl, and (NR a R b )carbonylalkyl;

R 3 and R 4 are independently selected from the group consisting of hydrogen, alkoxy, alkyl, halo, haloalkoxy, haloalkyl, and hydroxy;

L is selected from the group consisting of (CH 2 ) m N(R 7 )C(O)N(R 8 )(CH 2 ) n and CH 2 C(O)NR 7 , wherein m is 0 and n is 0, and wherein each group is drawn with its left end attached to the ring substituted with R 3 and R 4 ;

R 7 and R 8 are independently selected from the group consisting of hydrogen and alkyl;

R 9 is selected from the group consisting of hydrogen, alkenyl, alkoxyalkyl, alkyl, alkylcarbonyl, aryl, heterocyclylalkyl, hydroxyalkyl, and (NR a R b )alkyl;

R 10 and R 11 are independently selected from the group consisting of hydrogen, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, aryloxy, arylalkyl, carboxy, cyano, halo, haloalkoxy, haloalkyl, hydroxy, hydroxyalkyl, nitro, and —NR c R d ;

R a and R b are independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, and heterocyclylsulfonyl; and

R c and R d are independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl.

3. The compound of claim 2 wherein L is (CH 2 ) m N(R 7 )C(O)N(R 8 )(CH 2 ) n .

4. The compound of claim 3 selected from the group consisting of

N-[4-(3-amino-1,2-benzisothiazol-4-yl)phenyl]-N′-(3,5-dimethylphenyl)urea;

N-[4-(3-amino-1,2-benzisothiazol-4-yl)phenyl]-N′-(3-chlorophenyl)urea;

N-[4-(3-amino-1,2-benzisothiazol-4-yl)phenyl]-N′-(2-fluoro-5-methylphenyl)urea;

N-[4-(3-amino-1,2-benzisothiazol-4-yl)phenyl]-N′-(3-methylphenyl)urea; and

N-[4-(3-amino-1,2-benzisothiazol-4-yl)phenyl]-N′-[3-(trifluoromethyl)phenyl]urea.