Claims for Patent: 8,557,810

Summary for Patent: 8,557,810

Title:	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.
Inventor(s):	Shripad Bhagwat, Qi Chao, Robert M. Grotzfeld, Hitesh K. Patel, Kelly G. Sprankle
Assignee:	Ambit Bioscience Corp
Application Number:	US13/357,477
Patent Claims:	1. A pharmaceutical composition comprising a compound and hydroxypropyl-beta-cyclodextrin, wherein the compound corresponds to formula (I), wherein bond b is a single bond or double bond; X is —S—, —N(R5)— or —O—; Z1 and Z3 are each independently —N(R5)—, —(CH2)q—, —O—, —S—, or a direct bond; Z2 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; R0 is hydrogen, halo, hydroxy, optionally substituted alkyl, or optionally substituted alkoxy; each R1 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, —R6OR7, —R6SR7, —R6S(O)tR8, —R6N(R7)2, —R6—OR9OR7, —R6CN, —R6C(O)R7, —R6C(S)R7, —R6C(NR7)R7, —R6C(O)OR7, —R6C(S)OR7, —R6C(NR7)OR7, —R6C(O)N(R7)2, —R6C(S)N(R7)2, —R6C(NR7)N(R7)2, —R6C(O)N(R7)R9N(R7)2, —R6C(O)SR8, —R6C(S)SR8, —R6C(NR7)SR8, —R6S(O)tOR7, —R6S(O)tN(R7)2, —R6S(O)tN(R7)N(R7)2, —R6S(O)tN(R7)N═C(R7)2, —R6S(O)tN(R7)C(O)R8, —R6S(O)tN(R7)C(O)N(R7)2, —R6S(O)tN(R7)C(NR7)N(R7)2, —R6N(R7)C(O)R8, —R6N(R7)C(O)OR8, —R6N(R7)C(O)SR8, —R6N(R7)C(NR7)SR8, —R6N(R7)C(S)SR8, —R6N(R7)C(O)N(R7)2, —R6N(R7)C(NR7)N(R7)2, —R6N(R7)C(S)N(R7)2, —R6N(R7)S(O)tR8, —R6OC(O)R8, —R6OC(NR7)R8, —R6OC(S)R8, —R6OC(O)OR8, —R6OC(NR7)OR8, —R6OC(S)OR8, —R6OC(O)SR8, —R6OC(O)N(R7)2, —R6OC(NR7)N(R7)2, —R6OC(S)N(R7)2, —R6OR9N(R7)2, —R6SR9N(R7)2, —R6N(R7)R9N(R7)2, —R6C(O)R9C(O)R7, —R6C(O)R9C(S)R7, —R6C(O)R9C(NR7)R7, —R6C(O)R9C(O)OR7, —R6C(O)R9C(S)OR7, —R6C(O)R9C(NR7)OR7, —R6C(O)R9C(O)N(R7)2, —R6C(O)R9C(S)N(R7)2, —R6C(O)R9C(NR7)N(R7)2, —R6C(O)R9C(O)SR8, —R6C(O)R9C(S)SR8, —R6C(O)R9C(NR7)SR8, —R6OR9OR7, —R6C(O)R9N(R7)R9N(R7)2, —R6C(O)R9N(R7)R9OR7 and —R6C(O)N(R7)R9OR7; t is 1 or 2; each R2 is independently selected from hydrogen, halo, nitro, cyano, optionally substituted alkyl, —OR12, —SR12, —N(R12)2, —S(O)tR13, —C(O)R12, —C(O)OR12, —C(O)N(R12)2, —C(O)SR12, and —N(R12)S(O)tR13; R3 is hydrogen, halo, nitro, cyano, optionally substituted alkyl, —OR12, —SR12, —N(R12)2, —S(O)tR13, —C(O)R12, —C(O)OR12, —C(O)N(R12)2, —C(O)SR12, or —N(R12)S(O)tR13; R4 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 R5 is independently hydrogen, or optionally substituted alkyl; each R6 is independently a direct bond, an optionally substituted alkylene chain, or an optionally substituted alkenylene chain; each R7 is independently selected from (i) or (ii) below (i) R7 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 R7 groups together with the atom to which they are attached form an optionally substituted heterocyclyl or optionally substituted heteroaryl; R8 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 R9 is independently an optionally substituted alkylene chain or an optionally substituted alkenylene chain; each R12 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 R13 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 —Z1Z2Z3R4 is —NHC(O)Bu then R1 may not be ethoxy; (ii) if —Z1Z2Z3R4 is —C(O)ORp, where Rp is methyl, or ethyl, then R1 may not be hydroxyl, methoxy or methoxycarbonyl; (iii) if —Z1Z2Z3R4 is —NHC(O)C(O)ORp, where Rp is methyl, or ethyl, then R1 may not be methoxy; (iv) if —Z1Z2Z3R4 is —CH2C(O)ORp, where Rp is methyl, or ethyl, then R1 may not be methoxy or ethoxy; (v) if —Z1Z2Z3R4 is —OC(O)CH3, then R1 may not be methyl, methoxy or ethoxy; as a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or as a pharmaceutically acceptable salt thereof. 2. The composition of claim 1, wherein the composition is an aqueous solution. 3. The composition of claim 2, wherein the aqueous solution contains about 1% to about 50% hydroxypropyl-beta-cyclodextrin. 4. The composition of claim 2, wherein the aqueous solution contains about 1%, 3%, 5%, 10% or about 20% hydroxypropyl-beta-cyclodextrin. 5. The composition of claim 1, wherein the compound corresponds to formula (I), 6. The composition of claim 1, wherein the compound is a pharmaceutically acceptable salt of the compound of formula (I). 7. The composition of claim 1, wherein R4 is optionally substituted heterocyclyl or optionally substituted heteroaryl. 8. The composition of claim 1, wherein R4 is wherein R10 is hydrogen, alkyl, haloalkyl or haloaryl. 9. The composition of claim 1, wherein R4 is 10. A pharmaceutical composition comprising a compound and hydroxypropyl-beta-cyclodextrin, wherein the compound corresponds to formula (II): wherein: X is —S—, —N(R5)— or —O—; X1, X2, X3, X4 are each independently selected from —C(R10)—, —C(R10)2—, —N—, —N(R16)—, —O— and —S—, provided that no more than two of X1, X2, X3 and X4 are heteroatoms and wherein no two adjacent X's are both —O— or —S—; and each R10 is independently selected from hydrogen, halo, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R16 is independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl and optionally substituted heteroaryl; n is an integer from 1 to 3; R0 is hydrogen, halo, hydroxy, optionally substituted alkyl, or optionally substituted alkoxy; each R1 is independently selected from the group consisting of halo, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —R6OR7, —R6SR7, —R6S(O)tR8, —R6N(R7)2, —R6—OR9OR7, —R6CN, —R6C(O)R7, —R6C(S)R7, —R6C(NR7)R7, —R6C(O)OR7, —R6C(S)OR7, —R6C(NR7)OR7, —R6C(O)N(R7)2, —R6C(S)N(R7)2, —R6C(NR7)N(R7)2, —R6C(O)N(R7)R9N(R7)2, —R6C(O)SR8, —R6C(S)SR8, —R6C(NR7)SR8, —R6S(O)tOR7, —R6S(O)tN(R7)2, —R6S(O)tN(R7)N(R7)2, —R6S(O)tN(R7)N═C(R7)2, —R6S(O)tN(R7)C(O)R8, —R6S(O)tN(R7)C(O)N(R7)2, —R6S(O)tN(R7)C(NR7)N(R7)2, —R6N(R7)C(O)R8, —R6N(R7)C(O)OR8, —R6N(R7)C(O)SR8, —R6N(R7)C(NR7)SR8, —R6N(R7)C(S)SR8, —R6N(R7)C(O)N(R7)2, —R6N(R7)C(NR7)N(R7)2, —R6N(R7)C(S)N(R7)2, —R6N(R7)S(O)tR8, —R6OC(O)R8, —R6OC(NR7)R8, —R6OC(S)R8, —R6OC(O)OR8, —R6OC(NR7)OR8, —R6OC(S)OR8, —R6OC(O)SR8, —R6OC(O)N(R)2, —R6OC(NR7)N(R7)2, —R6OC(S)N(R7)2, —R6OR9N(R7)2, —R6SR9N(R7)2, —R6N(R7)R9N(R7)2, —R6C(O)R9C(O)R7, —R6C(O)R9C(S)R7, —R6C(O)R9C(NR7)R7, —R6C(O)R9C(O)OR7, —R6C(O)R9C(S)OR7, —R6C(O)R9C(NR7)OR7, —R6C(O)R9C(O)N(R7)2, —R6C(O)R9C(S)N(R7)2, —R6C(O)R9C(NR7)N(R7)2, —R6C(O)R9C(O)SR8, —R6C(O)R9C(S)SR8, —R6C(O)R9C(NR7)SR8, —R6OR9OR7, —R6C(O)R9N(R7)R9N(R7)2, —R6C(O)R9N(R7)R9OR7 and —R6C(O)N(R7)R9OR7; each R2 is independently selected from hydrogen, halo, nitro, cyano, optionally substituted alkyl, —OR12, —SR12, —N(R12)2, —S(O)tR13, —C(O)R12, —C(O)OR12, —C(O)N(R12)2, —C(O)SR12, and —N(R12)S(O)tR13; R3 is hydrogen, halo, nitro, cyano, optionally substituted alkyl, —OR12, —SR12, —N(R12)2, —S(O)tR13, —C(O)R12, —C(O)OR12, —C(O)N(R12)2, —C(O)SR12, or —N(R12)S(O)tR13; t is 1 or 2; and each R5 is independently hydrogen, or optionally substituted alkyl; each R6 is independently a direct bond, an optionally substituted alkylene chain, or an optionally substituted alkenylene chain; each R7 is independently selected from (i) or (ii) below (i) R7 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 (R7)s together with the atom to which they are attached form an optionally substituted heterocyclyl or optionally substituted heteroaryl; R8 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 R9 is independently an optionally substituted alkylene chain or an optionally substituted alkenylene chain; each R12 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 R13 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; as a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or as a pharmaceutically acceptable salt thereof. 11. The composition of claim 10, wherein the compound corresponds to formula (III): wherein: X is —S—, —N(R5)— or —O—; X1 is —C(R10)—, or —N—; X2 is —O— or —S—; where each R10 is independently selected from hydrogen, halo, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl and optionally substituted heteroaryl; and the remainder of n, R0, R1, R2, R3 and R5 are as defined in claim 10; as a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or as a pharmaceutically acceptable salt thereof. 12. The composition of claim 10, wherein the compound corresponds to formula (IIIa): as a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or as a pharmaceutically acceptable salt thereof. 13. The composition of claim 10, wherein the compound corresponds to formula (IV) wherein: K is —(CH2)q—, —C(O), —(CH2)qO—, —(CH2)qO(CH2)q—, —(CH2)qC(O)—, —(CH2)qC(O)NH(CH2)q—, —C(O)NH(CH2)q—, —O(CH2)q—, —OC(O)—, —OC(O)(CH2)q— or a direct bond; X is —S—, —N(R5)— or —O—; X1 is —C(R10)—, or —N—; X2 is —O— or —S—; Y is —O—, —S—, —S(O)—, —S(O)2—, —N(R14)—, —C(H)R15—, or —C(O)—; q is an integer from 1 to 4; p is an integer from 0 to 2; R10 is independently selected from hydrogen, halo, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted aryl; R14 is independently, hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, optionally substituted aryl, S(O)tR13, —C(O)R12, —C(O)OR12, —C(O)N(R12)2, or —C(O)SR12; R15 is independently, hydrogen, halo, nitro, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, optionally substituted aryl, —OR12, —SR12, —N(R12)2, —S(O)tR13, —C(O)R12, —C(O)OR12, —C(O)N(R12)2, —C(O)SR12, or —N(R12)S(O)tR13; t is 1 or 2; and as a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or as a pharmaceutically acceptable salt thereof. 14. The composition of claim 10, wherein the compound corresponds to formula (V): wherein K is —O(CH2)q—, —C(O), —C(O)NH(CH2)q—, —(CH2)qO—, or —(CH2)qO(CH2)q—; p is an integer from 0 to 2; each q is independently an integer from 1 to 4; X1 is —N—; X2 is —O—; Y is —O—, —S—, —N(R14)— or —C(H)R15—, m is 0, 1, or 2; R14 is hydrogen, optionally substituted alkyl, —C(O)OR12, —C(O)SR12, —C(O)NR12 or —S(O)tR13; R15 is hydrogen or optionally substituted alkyl; R13 is optionally substituted alkyl; and t is 1 or 2; as a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or as a pharmaceutically acceptable salt thereof. 15. The composition of claim 10, wherein the compound corresponds to formula (Va): wherein K is —O(CH2)q—, —(CH2)qO—, —(CH2)q— or —(CH2)qO(CH2)q—; each q is independently 1 to 4; Y is —O—, —S—, or —N(R14)—; R14 is hydrogen, optionally substituted lower alkyl, or —S(O)tR13; R13 is lower alkyl; and t is 1 or 2. 16. The composition of claim 1, 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. 17. A pharmaceutical composition comprising a compound and hydroxypropyl-beta-cyclodextrin, wherein the compound corresponds to formula 18. The composition of claim 17, wherein the composition is an aqueous solution. 19. The composition of claim 18, wherein the aqueous solution contains about 1% to about 50% hydroxypropyl-beta-cyclodextrin. 20. The composition of claim 18, wherein the aqueous solution contains about 1%, 3%, 5%, 10% or about 20% hydroxypropyl-beta-cyclodextrin. 21. A pharmaceutical composition comprising a compound and cyclodextrin, wherein the compound corresponds to formula (I), wherein bond b is a single bond or double bond; X is —S—, —N(R5)— or —O—; Z1 and Z3 are each independently —N(R5)—, —(CH2)q—, —O—, —S—, or a direct bond; Z2 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; R0 is hydrogen, halo, hydroxy, optionally substituted alkyl, or optionally substituted alkoxy; each R1 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, —R6OR7, —R6SR7, —R6S(O)tR8, —R6N(R7)2, —R6—OR9OR7, —R6CN, —R6C(O)R7, —R6C(S)R7, —R6C(NR7)R7, —R6C(O)OR7, —R6C(S)OR7, —R6C(NR7)OR7, —R6C(O)N(R7)2, —R6C(S)N(R7)2, —R6C(NR7)N(R7)2, —R6C(O)N(R7)R9N(R7)2, —R6C(O)SR8, —R6C(S)SR8, —R6C(NR7)SR8, —R6S(O)tOR7, —R6S(O)tN(R7)2, —R6S(O)tN(R7)N(R7)2, —R6S(O)tN(R7)N═C(R7)2, —R6S(O)tN(R7)C(O)R8, —R6S(O)tN(R7)C(O)N(R7)2, —R6S(O)tN(R7)C(NR7)N(R7)2, —R6N(R7)C(O)R8, —R6N(R7)C(O)OR8, —R6N(R7)C(O)SR8, —R6N(R7)C(NR7)SR8, —R6N(R7)C(S)SR8, —R6N(R7)C(O)N(R7)2, —R6N(R7)C(NR7)N(R7)2, —R6N(R7)C(S)N(R7)2, —R6N(R7)S(O)tR8, —R6OC(O)R8, —R6OC(NR7)R8, —R6OC(S)R8, —R6OC(O)OR8, —R6OC(NR7)OR8, —R6OC(S)OR8, —R6OC(O)SR8, —R6OC(O)N(R7)2, —R6OC(NR7)N(R7)2, —R6OC(S)N(R7)2, —R6OR9N(R7)2, —R6SR9N(R7)2, —R6N(R7)R9N(R7)2, —R6C(O)R9C(O)R7, —R6C(O)R9C(S)R7, —R6C(O)R9C(NR7)R7, —R6C(O)R9C(O)OR7, —R6C(O)R9C(S)OR7, —R6C(O)R9C(NR7)OR7, —R6C(O)R9C(O)N(R7)2, —R6C(O)R9C(S)N(R7)2, —R6C(O)R9C(NR7)N(R7)2, —R6C(O)R9C(O)SR8, —R6C(O)R9C(S)SR8, —R6C(O)R9C(NR7)SR8, —R6OR9OR7, —R6C(O)R9N(R7)R9N(R7)2, —R6C(O)R9N(R7)R9OR7 and —R6C(O)N(R7)R9OR7; t is 1 or 2; each R2 is independently selected from hydrogen, halo, nitro, cyano, optionally substituted alkyl, —OR12, —SR12, —N(R12)2, —S(O)tR13, —C(O)R12, —C(O)OR12, —C(O)N(R12)2, —C(O)SR12, and —N(R12)S(O)tR13; R3 is hydrogen, halo, nitro, cyano, optionally substituted alkyl, —OR12, —SR12, —N(R12)2, —S(O)tR13, —C(O)R12, —C(O)OR12, —C(O)N(R12)2, —C(O)SR12, or —N(R12)S(O)tR13; R4 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 R5 is independently hydrogen, or optionally substituted alkyl; each R6 is independently a direct bond, an optionally substituted alkylene chain, or an optionally substituted alkenylene chain; each R7 is independently selected from (i) or (ii) below (i) R7 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 R7 groups together with the atom to which they are attached form an optionally substituted heterocyclyl or optionally substituted heteroaryl; R8 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 R9 is independently an optionally substituted alkylene chain or an optionally substituted alkenylene chain; each R12 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 R13 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 —Z1Z2Z3R4 is —NHC(O)Bu then R1 may not be ethoxy; (ii) if —Z1Z2Z3R4 is —C(O)ORp, where Rp is methyl, or ethyl, then R1 may not be hydroxyl, methoxy or methoxycarbonyl; (iii) if —Z1Z2Z3R4 is —NHC(O)C(O)ORp, where Rp is methyl, or ethyl, then R1 may not be methoxy; (iv) if —Z1Z2Z3R4 is —CH2C(O)ORp, where Rp is methyl, or ethyl, then R1 may not be methoxy or ethoxy; (v) if —Z1Z2Z3R4 is —OC(O)CH3, then R1 may not be methyl, methoxy or ethoxy; as a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or as a pharmaceutically acceptable salt thereof. 22. A pharmaceutical composition comprising a compound and cyclodextrin, wherein the compound corresponds to formula