Claims for Patent: 7,820,657

Summary for Patent: 7,820,657

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:	US11/724,992
Patent Claims:	1. A compound of 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 compound of claim 1, wherein the compound is of formula (I), 3. The compound of claim 1, wherein the compound is a pharmaceutically acceptable salt of the compound of formula (I). 4. The compound of claim 1, wherein R4 is optionally substituted heterocyclyl or optionally substituted heteroaryl. 5. The compound of claim 1, wherein R4 is selected from wherein, each R10 is independently selected from hydrogen, halo, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl and optionally substituted heteroaryl. 6. The compound of claim 4, wherein R4 is wherein, each R10 is independently selected from hydrogen, halo, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl and optionally substituted heteroaryl. 7. The compound of claim 6, wherein R4 is wherein R10 is hydrogen, alkyl, haloalkyl or haloaryl. 8. The compound of claim 7, wherein R10 is hydrogen, methyl, tert-butyl, trifluoromethyl or p-chlorophenyl. 9. The compound of claim 7, wherein R4 is 10. The compound of claim 1, wherein -Z1Z2Z3- is —N(R5)C(O)N(R5)—, —N(R5)C(O)—, —C(O)N(R5)—, —OC(O)—, —C(O)O—, —N(R5)C(S)N(R5)—, —C(S)N(R5)—, —N(R5)C(S)—, —C(S)O— or —OC(S)— and each R5 is independently hydrogen or optionally substituted alkyl. 11. The compound of claim 1, wherein R4Z3Z2Z1- is R4N(R5)C(O)— or R4N(R5)C(S)—, and R5 is hydrogen, or optionally substituted alkyl. 12. The compound of claim 10, wherein bond b is a double bond and X is —S—. 13. The compound of claim 12, wherein R4 is a five-membered or six-membered heteroaryl selected from the group consisting of pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl and isothiazolyl. 14. The compound of claim 13, wherein R1 is where K is —C(O)—, —(CH2)q—, —(CH2)qO—, —(CH2)qO(CH2)q—, —(CH2)qC(O)—, —C(O)NH(CH2)q—, —C(O)NH(CH2)qNH(CH2)q—, —(CH2)qC(O)NH(CH2)q—, —O(CH2)q—, —OC(O)—, —OC(O)(CH2)q— or a direct bond; Y is —O—; p is an integer 1; and each q is independently 2 or 3. 15. The compound of claim 14, wherein the compound is selected from the group consisting of: 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; and 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. 16. The compound of claim 4, wherein the compound is morpholine-4-carboxylic acid {4-[7-(3-morpholin-4-yl-3-oxo-propyl)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-amide. 17. The compound of claim 1, wherein R4Z3Z2Z1- is R4N(R5)C(O)N(R5)— or R4N(R5)C(S)N(R5)—; and each R5 is independently hydrogen, or optionally substituted alkyl. 18. A compound corresponding 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(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; 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. 19. The compound of claim 18 corresponding to the 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 20; as a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or as a pharmaceutically acceptable salt thereof. 20. The compound of claim 18, wherein R1 is independently selected from the group consisting of halo, optionally substituted alkyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclyl, optionally substituted heteroaralkyl, optionally substituted heteroaryl, —R6OR7, —R6SR7, —R6S(O)tR8, —R6N(R7)2, —R6C(O)R7, —R6C(S)R7, —R6C(NR7)R7, —R6C(O)OR7, —R6C(O)N(R7)R9N(R7)2, —R6OC(O)R7, —R6C(NR7)OR7, —R6C(O)N(R7)2, —R6N(R7)C(O)R8, —R6OR9N(R7)2, —R6SR9N(R7)2, —R6N(R7)R9N(R7)2, —R6—OR9OR7, —R6—OR9N(R7)2, —R6C(O)R9N(R7)R9N(R7)2, —R6C(O)R9N(R7)R9OR7 and —R6C(O)N(R7)R9OR7 wherein: t is 1 or 2; 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 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, 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; and each R9 is independently an optionally substituted alkylene chain or an optionally substituted alkenylene chain. 21. The compound of claim 20, wherein R1 is —R6OR7, —R6SR7, —R6S(O)tR8, —R6N(R7)2, —R6C(O)R7, —R6C(S)R7, —R6C(NR7)R7, —R6C(O)OR7, —R6C(O)N(R7)R9N(R7)2, —R6OC(O)R7, —R6C(NR7)OR7, —R6C(O)N(R7)2, —R6N(R7)C(O)R8, —R6OR9N(R7)2, —R6SR9N(R7)2, —R6N(R7)R9N(R7)2, —R6OR9OR7, —R6OR9N(R7)2, —R6C(O)R9N(R7)R9N(R7)2, —R6C(O)R9N(R7)R9OR7 or —R6C(O)N(R7)R9OR7; and each R6 is independently a direct bond, an optionally substituted alkylene chain, or an optionally substituted alkenylene chain; and R7, when attached singly to an atom, is each 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 when attached doubly to the same atom, together forms an optionally substituted heterocyclyl or optionally substituted heteroaryl. 22. The compound of claim 19 corresponding to the formula (IIIa): as a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or as a pharmaceutically acceptable salt thereof. 23. The compound of claim 19 corresponding to the 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. 24. The compound of claim 23, wherein X1 is —N— and X2 is —O—. 25. The compound of claim 23, wherein Y is —N(R14); R14 is alkyl or —S(O)tR13; t is 1 or 2 and R13 is alkyl. 26. The compound of claim 25, wherein R14 is methyl, ethyl or —S(O)tR13; t is 2 and R13 is methyl. 27. The compound of claim 23, wherein the compound is of 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. 28. The compound of claim 27, wherein the compound is of 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. 29. The compound of claim 22, wherein R1 is halo, alkyl, —R6OR7, —R6N(R7)2, —R6C(O)OR7, —R9OR9OR7, —R6OR9N(R7)2, —R6C(O)N(R7)R9(R7)2, —R6C(O)R9N(R7)R9OR7 or —R6C(O)N(R7)R9OR7; and R7 is 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 or optionally substituted heteroaralkyl. 30. The compound of claim 29, wherein R1 is fluoro, methyl, ethyl, hydroxy, methoxy, diethylamino or carboxy. 31. The compound of claim 1 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[2,1b]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-Butyl-isoxazol-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-Butyl-isoxazol-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; and 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. 32. The compound of claim 1 selected from the group consisting of: 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, and 2-{4-[3-(5-tert-Butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazole-7-carboxylic acid. 33. The compound of claim 1 selected from the group consisting of: 1-(5-tert-Butyl-isoxazol-3-yl)-3-[4-(7-fluoro-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea; and 1-(5-tert-Butyl-isoxazol-3-yl)-3-[4-(7-methyl-benzo[d]imidazo[2,1-b]thiazol-2-yl)-phenyl]-urea. 34. A composition comprising an effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier, excipient or diluent. 35. The composition according to claim 34 further comprising a therapeutic agent selected from a chemotherapeutic agent, an anti-proliferative agent, an anti-inflammatory agent, an immunomodulatory agent and an immunosuppressive agent. 36. A compound of 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 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(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; 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; R4 is selected from the group consisting of 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; as a single stereoisomer, a mixture of stereoisomers, a racemic mixture of stereoisomers, or as a pharmaceutically acceptable salt thereof. 37. A compound of formula: