Imidazolothiazole compounds for the treatment of disease

Abstract

Compounds, compositions and methods are provided for modulating the activity of receptor kinases and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by receptor kinases.

1 - 37 . (canceled) 
     
     
         38 . A method of treating an autoimmune disease in a patient comprising administrating to the patient a therapeutically effective amount of a compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 bond b is a single bond or double bond; 
 X is —S—, —N(R 5 )— or —O—; 
 Z 1  and Z 3  are each independently —N(R 5 )—, —(CH 2 ) q —, —O—, —S—, or a direct bond; 
 Z 2  is —C(O)— or —C(S)—; 
 m is an integer from 1 to 2; 
 n is an integer from 1 to 3; 
 each q is independently an integer from 1 to 4: 
 R 0  is hydrogen, halo, hydroxy, optionally substituted alkyl, or optionally substituted alkoxy; 
 each R 1  is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —R 6 OR 7 , —R 6 SR 7 , —R 6 S(O) t R 8 , —R 6 N(R 7 ) 2 , —R 6 —OR 9 OR 7 , —R 6 CN, —R 6 C(O)R 7 , —R 6 C(S)R 7 , —R 6 C(NR 7 )R 7 , —R 6 C(O)OR 7 , —R 6 C(S)OR 7 , —R 6 C(NR 7 )OR 7 , —R 6 C(O)N(R 7 ) 2 , —R 6 C(S)N(R 7 ) 2 , —R 6 C(NR 7 )N(R 7 ) 2 , —R 6 C(O)N(R 7 )R 9 N(R 7 ) 2 , —R 6 C(O)SR 8 , —R 6 C(S)SR 8 , —R 6 C(NR 7 )SR 8 , —R 6 S(O) t OR 7 , —R 6 S(O) t N(R 7 ) 2 , —R 6 S(O) t N(R 7 )N(R 7 ) 2 , —R 6 S(O) t N(R 7 )N═C(R 7 ) 2 , —R 6 S(O) t N(R 7 )C(O)R 8 , —R 6 S(O) t N(R 7 )C(O)N(R 7 ) 2 , —R 6 S(O) t N(R 7 )C(NR 7 )N(R 7 ) 2 , —R 6 N(R 7 )C(O)R 8 , —R 6 N(R 7 )C(O)OR 8 , —R 6 N(R 7 )C(O)SR 8 , —R 6 N(R 7 )C(NR 7 )SR 8 , —R 6 N(R 7 )C(S)SR 8 , —R 6 N(R 7 )C(O)N(R 7 ) 2 , —R 6 N(R 7 )C(NR 7 )N(R 7 ) 2 , —R 6 N(R 7 )C(S)N(R 7 ) 2 , —R 6 N(R 7 )S(O) t R 8 , —R 6 OC(O)R 8 , —R 6 OC(NR 7 )R 8 , —R 6 OC(S)R 8 , —R 6 OC(O)OR 8 , —R 6 OC(NR 7 )OR 8 , —R 6 OC(S)OR 8 , —R 6 OC(O)SR 8 , —R 6 OC(O)N(R 7 ) 2 , —R 6 OC(NR 7 )N(R 7 ) 2 , —R 6 OC(S)N(R 7 ) 2 , —R 6 OR N(R 7 ) 2 , —R 6 SR 9 N(R 7 ) 2 , —R 6 N(R 7 )RN(R(R 7 ) 2 , —R 6 C(O)R 9 C(O)R 7 , —R 6 C(O)R 9 C(S)R 7 , —R 6 C(O)R 9 C(NR 7 )R 7 , —R 6 C(O)R 9 C(O)OR 7 , —R 6 C(O)R 9 C(S)OR 7 , —R 6 C(O)R 9 C(NR 7 )OR 7 , —R 6 C(O)R 9 C(O)N(R 7 ) 2 , —R 6 C(O)R 9 C(S)N(R 7 ) 2 , —R 6 C(O)R 9 C(NR 7 )N(R 7 ) 2 , —R 6 C(O)R 9 C(O)SR 8 , —R 6 C(O)R 9 C(S)SR 8 , —R 6 C(O)R 9 C(NR 7 )SR 8 , —R 6 OR 9 OR 7 , —R 6 C(O)R 9 N(R 7 )R 9 N(R 7 ) 2 , —R 6 C(O)R 9 N(R 7 )R 9 OR 7  and —R 6 C(O)N(R 7 )R 9 OR 7 ; 
 t is 1 or 2; 
 each R 2  is independently selected from hydrogen, halo, nitro, cyano, optionally substituted alkyl, —OR 12 , —SR 12 , —N(R 12 ) 2 , —S(O) t R 13 , —C(O)R 12 , —C(O)OR 12 , —C(O)N(R 12 ) 2 , —C(O)SR 12 , and —N(R 12 )S(O) t R 13 ; 
 R 3  is hydrogen, halo, nitro, cyano, optionally substituted alkyl, —OR 12 , —SR 12 , —N(R 12 ) 2 , —S(O) t R 13 , —C(O)R 12 , —C(O)OR 12 , —C(O)N(R 12 ), —C(O)SR 12 , or —N(R 12 )S(O) t R 13 ; 
 R 4  is selected from the group consisting of optionally substituted alkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, and optionally substituted aryl; 
 each R 5  is independently hydrogen, or optionally substituted alkyl; 
 each R 6  is independently a direct bond, an optionally substituted alkylene chain, or an optionally substituted alkenylene chain; 
 each R 7  is independently selected from (i) or (ii) below 
 (i) R 7  is selected from a group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl, or 
 (ii) two R 7  groups together with the atom to which they are attached form an optionally substituted heterocyclyl or optionally substituted heteroaryl; 
 R 8  is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; 
 each R 9  is independently an optionally substituted alkylene chain or an optionally substituted alkenylene chain; 
 each R 12  is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; and 
 R 13  is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; 
 with the proviso that, 
 (i) if —Z 1 Z 2 Z 3 R 4  is —NHC(O)Bu then R 1  may not be ethoxy; 
 (ii) if —Z 1 Z 2 Z 3 R 4  is —C(O)OR p , where R p  is methyl, or ethyl, then R 1  may not be hydroxyl, methoxy or methoxycarbonyl; 
 (iii) if —Z 1 Z 2 Z 3 R 4  is —NHC(O)C(O)OR p , where R p  is methyl, or ethyl, then R 1  may not be methoxy; 
 (iv) if —Z 1 Z 2 Z 3 R 4  is —CH 2 C(O)OR p , where R p  is methyl, or ethyl, then R 1  may not be methoxy or ethoxy; 
 (v) if —Z 1 Z 2 Z 3 R 4  is —OC(O)CH 3 , then R 1  may not be methyl, methoxy or ethoxy; 
 
       or a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. 
     
     
         39 . The method of  claim 38 , wherein the autoimmune disease is rheumatoid arthritis, lupus, multiple sclerosis, thyroiditis, type 1 diabetes, sarcoidosis, inflammatory bowel disease, Crohn's disease or systemic lupus. 
     
     
         40 . A method of treating an inflammatory disease in a patient comprising administrating to the patient a therapeutically effective amount of a compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 bond b is a single bond or double bond; 
 X is —S—, —N(R 5 )— or —O—; 
 Z 1  and Z 3  are each independently —N(R 5 )—, —(CH 2 ) q —, —O—, —S—, or a direct bond; 
 Z 2  is —C(O)— or —C(S)—; 
 m is an integer from 1 to 2; 
 n is an integer from 1 to 3; 
 each q is independently an integer from 1 to 4: 
 R 0  is hydrogen, halo, hydroxy, optionally substituted alkyl, or optionally substituted alkoxy; 
 each R 1  is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —R 6 OR 7 , —R 6 SR 7 , —R 6 S(O) t R 8 , —R 6 N(R 7 ) 2 , —R 6 —OR 9 OR 7 , —R 6 CN, —R 6 C(O)R 7 , —R 6 C(S)R 7 , —R 6 C(NR 7 )R 7 , —R 6 C(O)OR 7 , —R 6 C(S)OR 7 , —R 6 C(NR 7 )OR 7 , —R 6 C(O)N(R 7 ) 2 , —R 6 C(S)N(R 7 ) 2 , —R 6 C(NR 7 )N(R 7 ) 2 , —R 6 C(O)N(R 7 )R 9 N(R 7 ) 2 , —R 6 C(O)SR 8 , —R 6 C(S)SR 8 , —R 6 C(NR 7 )SR 8 , —R 6 S(O) t OR 7 , —R 6 S(O) t N(R 7 ) 2 , —R 6 S(O) t N(R 7 )N(R 7 ) 2 , —R 6 S(O) t N(R 7 )N═C(R 7 ) 2 , —R 6 S(O) t N(R 7 )C(O)R 8 , —R 6 S(O) t N(R 7 )C(O)N(R 7 ) 2 , —R 6 S(O) t N(R 7 )C(NR 7 )N(R 7 ) 2 , —R 6 N(R 7 )C(O)R 8 , —R 6 N(R 7 )C(O)OR 8 , —R 6 N(R 7 )C(O)SR 8 , —R 6 N(R 7 )C(NR 7 )SR 8 , —R 6 N(R 7 )C(S)SR 8 , —R 6 N(R 7 )C(O)N(R 7 ) 2 , —R 6 N(R 7 )C(NR 7 )N(R 7 ) 2 , —R 6 N(R 7 )C(S)N(R 7 ) 2 , —R 6 N(R 7 )S(O) t R 8 , —R 6 OC(O)R 8 , —R 6 OC(NR 7 )R 8 , —R 6 OC(S)R 8 , —R 6 OC(O)OR 8 , —R 6 OC(NR 7 )OR 8 , —R 6 OC(S)OR 8 , —R 6 OC(O)SR 8 , —R 6 OC(O)N(R 7 ) 2 , —R 6 OC(NR 7 )N(R 7 ) 2 , —R 6 OC(S)N(R 7 ) 2 , —R 6 OR 9 N(R 7 ) 2 , —R 6 SR 9 N(R 7 ) 2 , —R 6 N(R 7 )R 9 N(R 7 ) 2 , —R 6 C(O)R 9 C(O)R 7 , —R 6 C(O)R 9 C(S)R 7 , —R 6 C(O)R 9 C(NR 7 )R 7 , —R 6 C(O)R 9 C(O)OR 7 , —R 6 C(O)R 9 C(S)OR 7 , —R 6 C(O)R 9 C(NR 7 )OR 7 , —R 6 C(O)R 9 C(O)N(R 7 ) 2 , —R 6 C(O)R 9 C(S)N(R 7 ) 2 , —R 6 C(O)R 9 C(NR 7 )N(R 7 ) 2 , —R 6 C(O)R 9 C(O)SR 8 , —R 6 C(O)R 9 C(S)SR 8 , —R 6 C(O)R 9 C(NR 7 )SR 8 , —R 6 OR 9 OR 7 , —R 6 C(O)R 9 N(R 7 )R 9 N(R 7 ) 2 , —R 6 C(O)R 9 N(R 7 )R 9 OR 7  and —R 6 C(O)N(R 7 )R 9 OR 7 ; 
 t is 1 or 2; 
 each R 2  is independently selected from hydrogen, halo, nitro, cyano, optionally substituted alkyl, —OR 12 , —SR 12 , —N(R 12 ) 2 , —S(O) t R 13 , —C(O)R 12 , —C(O)OR 12 , —C(O)N(R 12 ) 2 , —C(O)SR 12 , and —N(R 12 )S(O) t R 13 ; 
 R 3  is hydrogen, halo, nitro, cyano, optionally substituted alkyl, —OR 12 , —SR 12 , —N(R 12 ) 2 , —S(O) t R 13 , —C(O)R 12 , —C(O)OR 12 , —C(O)N(R 12 ) 2 , —C(O)SR 12 , or —N(R 12 )S(O) t R 3 ; 
 R 4  is selected from the group consisting of optionally substituted alkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, and optionally substituted aryl; 
 each R 5  is independently hydrogen, or optionally substituted alkyl; 
 each R 6  is independently a direct bond, an optionally substituted alkylene chain, or an optionally substituted alkenylene chain; 
 each R 7  is independently selected from (i) or (ii) below 
 (i) R 7  is selected from a group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl, or 
 (ii) two R 7  groups together with the atom to which they are attached form an optionally substituted heterocyclyl or optionally substituted heteroaryl; 
 R 8  is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; 
 each R 9  is independently an optionally substituted alkylene chain or an optionally substituted alkenylene chain; 
 each R 12  is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; and 
 R 13  is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; 
 with the proviso that, 
 (i) if —Z 1 Z 2 Z 3 R 4  is —NHC(O)Bu then R 1  may not be ethoxy; 
 (ii) if —Z 1 Z 2 Z 3 R 4  is —C(O)OR p , where R is methyl, or ethyl, then R 1  may not be hydroxyl, methoxy or methoxycarbonyl; 
 (iii) if —Z 1 Z 2 Z 3 R 4  is —NHC(O)C(O)OR p , where R p  is methyl, or ethyl, then R 1  may not be methoxy; 
 (iv) if —Z 1 Z 2 Z 3 R 4  is —CH 2 C(O)OR p , where R p  is methyl, or ethyl, then R 1  may not be methoxy or ethoxy; 
 (v) if —Z 1 Z 2 Z 3 R 4  is —OC(O)CH 3 , then R 1  may not be methyl, methoxy or ethoxy; 
 
       or a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. 
     
     
         41 . (canceled) 
     
     
         42 . The method of  claim 38 , wherein the disease is a FLT3-mediated disease, KIT-mediated disease, RET-mediated disease, PDGFR-mediated disease, VEGFR-mediated disease or a CSF-1R-mediated disease. 
     
     
         43 . The method of  claim 40 , wherein the disease is a FLT3-mediated disease, KIT-mediated disease, RET-mediated disease, PDGFR-mediated disease, VEGFR-mediated disease or a CSF-1R-mediated disease. 
     
     
         44 - 45 . (canceled) 
     
     
         46 . The method of  claim 38 , wherein the compound is a pharmaceutically acceptable salt of the compound of formula (I). 
     
     
         47 . The method of  claim 46 , wherein the compound is of formula (III): 
       
         
           
           
               
               
           
         
         wherein: 
         X is —S—, —N(R 5 )— or —O—; 
         X 1  is —C(R 10 )—, or —N—; 
         X 2  is —O— or —S—; 
         where each R 10  is independently selected from hydrogen, halo, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl and optionally substituted heteroaryl; 
         or a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         48 . The method of  claim 47 , wherein the compound is of formula (IV) 
       
         
           
           
               
               
           
         
         wherein: 
         K is —(CH 2 ) q —, —C(O), —(CH 2 ) q O—, —(CH 2 ) q O(CH 2 ) q —, —(CH 2 ) q C(O)—, —(CH 2 ) q C(O)NH(CH 2 ) q —, —C(O)NH(CH 2 ) q —, —O(CH 2 ) q —, —OC(O)—, —OC(O)(CH 2 ) q — or a direct bond; 
         X is —S—, —N(R 5 )— or —O—; 
         X 1  is —C(R 10 )—, or —N—; 
         X 2  is —O— or —S—; 
         Y is —O—, —S—, —S(O)—, —S(O) 2 —, —N(R 14 )—, —C(H)R 15 , or —C(O)—; 
         q is an integer from 1 to 4; 
         p is an integer from 0 to 2; 
         R 10  is independently selected from hydrogen, halo, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted aryl; 
         R 14  is independently, hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, optionally substituted aryl, —S(O) t R 13 , —C(O)R 12 , —C(O)OR 12 , —C(O)N(R 12 ) 2 , or —C(O)SR 12 ; 
         R 15  is independently, hydrogen, halo, nitro, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, optionally substituted aryl, —OR 12 , —SR 12 , —N(R 12 ) 2 , —S(O) t R 13 , —C(O)R 12 , —C(O)OR 12 , —C(O)N(R 12 ) 2 , —C(O)SR 12 , or —N(R 12 )S(O) t R 13 ; 
         t is 1 or 2; and 
         or a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         49 . The method of  claim 48 , wherein the compound is of formula (V): 
       
         
           
           
               
               
           
         
         wherein K is —O(CH 2 ) q —, —C(O), —C(O)NH(CH 2 ) q —, —(CH 2 ) q O—, or —(CH 2 ) q O(CH 2 ) q —; 
         p is an integer from 0 to 2; 
         each q is independently an integer from 1 to 4; 
         X 1  is —N—; 
         X 2  is —O—; 
         Y is —O—, —S—, —N(R 14 )— or —C(H)R 15 —, 
         m is 0, 1, or 2; 
         R 14  is hydrogen, optionally substituted alkyl, —C(O)OR 12 , —C(O)SR 12 , —C(O)NR 12  or —S(O) t R 13 ; 
         R 15  is hydrogen or optionally substituted alkyl; 
         R 13  is optionally substituted alkyl; and 
         t is 1 or 2; 
         or a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         50 . The method of  claim 49 , wherein the compound is of formula (Va): 
       
         
           
           
               
               
           
         
         wherein K is —O(CH 2 ) q —, —(CH 2 ) q O—, —(CH 2 ) q — or —(CH 2 ) q O(CH 2 ) q —; 
         each q is independently 1 to 4; 
         Y is —O—, —S—, or —N(R 14 )—; 
         R 14  is hydrogen, optionally substituted lower alkyl, or —S(O) t R 13 ; 
         R 13  is lower alkyl; and 
         t is 1 or 2. 
       
     
     
         51 . The method of  claim 38 , wherein the compound is selected from the group consisting of:
 3-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-morpholin-4-yl-ethyl)-propionamide;   3-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-piperidin-1-yl-ethyl)-propionamide;   3-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(4-methyl-piperazin-1-yl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-(4-{7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-benzo[d]imidazo[2,1-b]thiazol-2-yl}-phenyl)-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-piperidin-1-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(3-morpholin-4-yl-propoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-(4-{7-[3-(4-methyl-piperazin-1-yl)-propoxy]-benzo[d]imidazo[2,1-b]thiazol-2-yl}-phenyl)-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-(4-{7-[3-(4-methanesulfonyl-piperazin-1-yl)-propoxy]-benzo[d]imidazo[2,1-b]thiazol-2-yl}-phenyl)-urea;   N-(5-tert-butyl-isoxazol-3-yl)-N′-(4-{7-[3-(4-ethyl-piperazin-1-yl)propyl]imidazo[2,1-b][1,3]benzothiazol-2-yl}phenyl)urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(3-morpholin-4-yl-3-oxo-propyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   3-(5-tert-butyl-isoxazol-3-yl)-1-methyl-1-{4-[7-(3-morpholin-4-yl-propyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(3-morpholin-4-yl-propyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl)}-urea;   N-(5-tert-butyl-isoxazol-3-yl)-N′-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-morpholin-4-yl-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   N-(5-tert-butyl-isoxazol-3-yl)-N′-{4-[7-(3-piperidin-1-yl-propyl)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea;   N-(5-tert-butyl-isoxazol-3-yl)-N′-{4-[5-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea;   2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-morpholin-4-yl-ethyl)-acetamide;   2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-piperidin-1-yl-ethyl)-acetamide;   2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-pyrrolidin-1-yl-ethyl)-acetamide;   1-(5-tert-butyl-isoxazol-3-yl)-3-(4-{7-[2-(4-ethyl-piperazin-1-yl)-2-oxo-ethyl]-benzo[d]imidazo[2,1-b]thiazol-2-yl)}-phenyl)-urea and   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-morpholin-4-ylmethyl-imidazo[2,1-b][1,3]benzothiazol-2-yl)-phenyl]-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(4-ethyl-piperazin-1-ylmethyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl})-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-piperidin-1-ylmethyl-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-morpholin-4-yl-2-oxo-ethyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl})-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-morpholin-4-yl-ethyl)-imidazo[2,1-b][1,3]benzothiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-piperidin-1-yl-ethyl)-imidazo[2,1-b][1,3]benzothiazol-2-yl]-phenyl}-urea;   1-(5-tert-butylisoxazol-3-yl)-3-(4-{7-[2-(4-ethyl-piperazin-1-yl)-ethyl]-imidazo[2,1-b][1,3]benzothiazol-2-yl}-phenyl)-urea;   N-(5-tert-butylisoxazol-3-yl)-N′-{4-[6-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid (2-morpholin-4-yl-ethyl)-amide;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid (2-piperidin-1-yl-ethyl)-amide;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid (2-diethylamino-ethyl)-amide;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(4-ethyl-piperazine-1-carbonyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(piperazine-1-carbonyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(4-methyl-piperazine-1-carbonyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-hydroxy-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-methoxy-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-diethylamino-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   ethyl {2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl}amino)phenyl] imidazo [2,1-b][1,3]benzothiazol-7-yl}acetate;   3-{2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl}amino) phenyl]imidazo[2,1-b][1,3]benzothiazol-7-yl} acetic acid;   pyrrolidine-2-carboxylic acid 2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl ester;   ethyl 3-{2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl} amino)phenyl] imidazo [2,1-b][1,3]benzothiazol-7-yl}propanoate;   3-{2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl} amino)phenyl] imidazo[2,1-b][1,3]benzothiazol-7-yl}propanoic acid;   3-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N,N-diethyl-propionamide;   2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-diethylamino-ethyl)-acetamide;   3-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-diethylamino-ethyl)-propionamide;   2-amino-3-methyl-butyric acid 2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl ester;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid ethyl ester;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-fluoro-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-methyl-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   2-benzo[d]isoxazol-3-yl-N-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-acetamide;   2-methyl-4-trifluoromethyl-thiazole-5-carboxylic acid {4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-amide;   2-(4-chloro-phenyl)-4-methyl-thiazole-5-carboxylic acid {4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-amide; and   morpholine-4-carboxylic acid {4-[7-(3-morpholin-4-yl-3-oxo-propyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-amide;   
       or a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. 
     
     
         52 . The method of  claim 38 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         53 . The method of  claim 38 , wherein the compound is a pharmaceutically acceptable salt of the compound of formula (I). 
     
     
         54 . The method of  claim 40 , wherein the compound is of formula (III): 
       
         
           
           
               
               
           
         
         wherein: 
         X is —S—, —N(R 5 )— or —O—; 
         X 1  is —C(R 10 )—, or —N—; 
         X 2  is —O— or —S—; 
         where each R 10  is independently selected from hydrogen, halo, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl and optionally substituted heteroaryl; 
         or a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         55 . The method of  claim 54 , wherein the compound is of formula (IV) 
       
         
           
           
               
               
           
         
         wherein: 
         K is —(CH 2 ) q —, —C(O), —(CH 2 ) q O—, —(CH 2 ) q O(CH 2 ) q —, —(CH 2 ) q C(O)—, —(CH 2 ) q C(O)NH(CH 2 ) q —, —C(O)NH(CH 2 ) q —, —O(CH 2 ) q —, —OC(O)—, —OC(O)(CH 2 ) q — or a direct bond; 
         X is —S—, —N(R 5 )— or —O—; 
         X 1  is —C(R 10 )—, or —N—; 
         X 2  is —O— or —S—; 
         Y is —O—, —S—, —S(O)—, —S(O) 2 —, —N(R 14 )—, —C(H)R 15 —, or —C(O)—; 
         q is an integer from 1 to 4; 
         p is an integer from 0 to 2; 
         R 10  is independently selected from hydrogen, halo, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted aryl; 
         R 14  is independently, hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, optionally substituted aryl, —S(O) t R 13 , —C(O)R 12 , —C(O)OR 12 , —C(O)N(R 12 ) 2 , or —C(O)SR 12 ; 
         R 15  is independently, hydrogen, halo, nitro, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, optionally substituted aryl, —OR 12 , —SR 12 , —N(R 12 ) 2 , —S(O) t R 13 , —C(O)R 12 , —C(O)OR 12 , —C(O)N(R 12 ) 2 , —C(O)SR 12 , or —N(R 12 )S(O) t R 13 ; 
         t is 1 or 2; and 
         or a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         56 . The method of  claim 55 , wherein the compound is of formula (V): 
       
         
           
           
               
               
           
         
         wherein K is —O(CH 2 ) q —, —C(O), —C(O)NH(CH 2 ) q —, —(CH 2 ) q O—, or —(CH 2 ) q O(CH 2 ) q —; 
         p is an integer from 0 to 2; 
         each q is independently an integer from 1 to 4; 
         X 1  is —N—; 
         X 2  is —O—; 
         Y is —O—, —S—, —N(R 14 )— or —C(H)R 15 —, 
         m is 0, 1, or 2; 
         R 14  is hydrogen, optionally substituted alkyl, —C(O)OR 12 , —C(O)SR 12 , —C(O)NR 12  or —S(O) t R 13 ; 
         R 15  is hydrogen or optionally substituted alkyl; 
         R 13  is optionally substituted alkyl; and 
         t is 1 or 2; 
         or a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         57 . The method of  claim 56 , wherein the compound is of formula (Va): 
       
         
           
           
               
               
           
         
         wherein K is —O(CH 2 ) q —, —(CH 2 ) q O—, —(CH 2 ) q — or —(CH 2 ) q O(CH 2 ) q —; 
         each q is independently 1 to 4; 
         Y is —O—, —S—, or —N(R 14 )—; 
         R 14  is hydrogen, optionally substituted lower alkyl, or —S(O) t R 13 ; 
         R 13  is lower alkyl; and 
         t is 1 or 2. 
       
     
     
         58 . The method of  claim 40 , wherein the compound is selected from the group consisting of:
 3-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-morpholin-4-yl-ethyl)-propionamide;   3-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-piperidin-1-yl-ethyl)-propionamide;   3-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(4-methyl-piperazin-1-yl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-(4-{7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-benzo[d]imidazo[2,1-b]thiazol-2-yl}-phenyl)-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-piperidin-1-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(3-morpholin-4-yl-propoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-(4-{7-[3-(4-methyl-piperazin-1-yl)-propoxy]-benzo[d]imidazo[2,1-b]thiazol-2-yl}-phenyl)-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-(4-{7-[3-(4-methanesulfonyl-piperazin-1-yl)-propoxy]-benzo[d]imidazo[2,1-b]thiazol-2-yl}-phenyl)-urea;   N-(5-tert-butyl-isoxazol-3-yl)-N′-(4-{7-[3-(4-ethyl-piperazin-1-yl)propyl]imidazo[2,1-b][1,3]benzothiazol-2-yl}phenyl)urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(3-morpholin-4-yl-3-oxo-propyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   3-(5-tert-butyl-isoxazol-3-yl)-1-methyl-1-{4-[7-(3-morpholin-4-yl-propyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(3-morpholin-4-yl-propyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   N-(5-tert-butyl-isoxazol-3-yl)-N′-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-morpholin-4-yl-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   N-(5-tert-butyl-isoxazol-3-yl)-N′-{4-[7-(3-piperidin-1-yl-propyl)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea;   N-(5-tert-butyl-isoxazol-3-yl)-N′-{4-[5-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea;   2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-morpholin-4-yl-ethyl)-acetamide;   2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-piperidin-1-yl-ethyl)-acetamide;   2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-pyrrolidin-1-yl-ethyl)-acetamide;   1-(5-tert-butyl-isoxazol-3-yl)-3-(4-{7-[2-(4-ethyl-piperazin-1-yl)-2-oxo-ethyl]-benzo[d]imidazo[2,1-b]thiazol-2-yl}-phenyl)-urea and   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-morpholin-4-ylmethyl-imidazo[2,1-b][1,3]benzothiazol-2-yl)-phenyl]-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(4-ethyl-piperazin-1-ylmethyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl})-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-piperidin-1-ylmethyl-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-morpholin-4-yl-2-oxo-ethyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl})-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-morpholin-4-yl-ethyl)-imidazo[2,1-b][1,3]benzothiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-piperidin-1-yl-ethyl)-imidazo[2,1-b][1,3]benzothiazol-2-yl]-phenyl}-urea;   1-(5-tert-butylisoxazol-3-yl)-3-(4-{7-[2-(4-ethyl-piperazin-1-yl)-ethyl]-imidazo[2,1-b][1,3]benzothiazol-2-yl}-phenyl)-urea;   N-(5-tert-butylisoxazol-3-yl)-N′-{4-[6-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid (2-morpholin-4-yl-ethyl)-amide;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid (2-piperidin-1-yl-ethyl)-amide;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid (2-diethylamino-ethyl)-amide;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(4-ethyl-piperazine-1-carbonyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(piperazine-1-carbonyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(4-methyl-piperazine-1-carbonyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-hydroxy-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-methoxy-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-diethylamino-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea;   ethyl {2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl}amino)phenyl] imidazo [2,1-b][1,3]benzothiazol-7-yl}acetate;   3-{2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl}amino) phenyl]imidazo[2,1-b][1,3]benzothiazol-7-yl} acetic acid;   pyrrolidine-2-carboxylic acid 2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl ester;   ethyl 3-{2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl} amino)phenyl] imidazo [2,1-b][1,3]benzothiazol-7-yl}propanoate;   3-{2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl} amino)phenyl] imidazo[2,1-b][1,3]benzothiazol-7-yl}propanoic acid;   3-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N,N-diethyl-propionamide;   2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-diethylamino-ethyl)-acetamide;   3-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl)-N-(2-diethylamino-ethyl)-propionamide;   2-amino-3-methyl-butyric acid 2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yl ester;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid ethyl ester;   2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-fluoro-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   1-(5-tert-butyl-isoxazol-3-yl)-3-[4-(7-methyl-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea;   2-benzo[d]isoxazol-3-yl-N-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-acetamide;   2-methyl-4-trifluoromethyl-thiazole-5-carboxylic acid {4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-amide;   2-(4-chloro-phenyl)-4-methyl-thiazole-5-carboxylic acid {4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-amide; and   morpholine-4-carboxylic acid {4-[7-(3-morpholin-4-yl-3-oxo-propyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-amide;   
       or a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or a pharmaceutically acceptable salt thereof. 
     
     
         59 . The method of  claim 40 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.