Chemical compounds

1. A compound of Formula (I):

or a salt or solvate, thereof:

wherein:

E is

unsubstituted heteroaryl, or

heteroaryl substituted with R 1 , or

heteroaryl substituted by R 1 and R 2 , or

R 1 and R 2 together with the atoms of E to which they are attached form a cycloalkyl, aryl, or heterocyclic ring fused to E;

A is aryl, heteroaryl, or heterocyclic;

X is S, O, S(O) 2 , S(O), C(H) 2 , C(H)(OH), or C(O);

Z is O or S;

p is 0 or 1;

q is 0 or 1;

the dotted line bonds “---” attached to Q and N′ represent a single bond or a double bond wherein when q is 0 the dotted line bond “---” attached to Q is a single bond and the dotted line bond attached to N′ is a double bond, and when q is 1 the dotted line bond “---” attached to Q is a double bond and the dotted line bond attached to N′ is a single bond; and

the dotted line within the 6 membered ring containing D, M, and T represents appropriate aromatic bonds;

D is CH, T is CR 8 , M is C and Q is N(R 7 ) p , wherein p is 0 and q is 1; or

D is CH, T is CR 8 , M is C and Q is N(R 7 ) p , wherein p is 1 and q is 0;

R 1 is C 1 –C 6 alkyl, C 1 –C 6 haloalkyl, aryl, heteroaryl, heterocyclic, halogen, C 1 –C 6 alkoxy, C 1 –C 6 haloalkoxy, aralkyl, aralkoxy, aryloxy, C 1 –C 6 alkylsulfanyl, C 1 –C 6 haloalkylsulfanyl, C 1 –C 6 alkylsulfenyl, C 1 –C 6 alkylsulfonyl, —NO 2 , —NR 4 R 5 , —C(O)OR 6 , —CN, —C(O)NR 4 R 5 , —S(O) 2 NR 4 R 5 , or cyanoalkyl;

R 2 is hydrogen, C 1 –C 6 alkyl, C 1 –C 6 haloalkyl, aryl, heteroaryl, heterocyclic, aralkyl, aralkoxy, aryloxy, halogen, C 1 –C 6 alkoxy, C 1 –C 6 haloalkoxy, C 1 –C 6 alkylsulfanyl, C 1 –C 6 haloalkylsulfanyl, C 1 –C 6 alkylsulfenyl, C 1 –C 6 alkylsulfonyl, oxo, hydroxy, —NO 2 , —NR 4 R 5 , —C(O)OR 6 , —CN, —C(O)NR 4 R 5 , —S(O) 2 NR 4 R 5 , or cyanoalkyl;

R 3 is hydrogen, C 1 –C 6 alkyl, aryl, aralkyl, aralkoxy, heteroaryl, heterocyclic, —RR 6 , —RNR 4 R 5 , —C(O) R 6 , —C(O)NR 4 R 5 , —C(O)OR 6 , —C(O)RO R 6 , —C(O)RC(O)OR 6 , —C(O)R R 6 , —C(O)RR′R 6 , —C(O)ROR′OR″O R 6 , —C(O)ROR′O R 6 , —C(O)RNR 4 R 5 , —C(O)RNR 4 C(O) R 6 , —C(O)RNR 4 C(O)OR 6 , —C(O)ORNR 4 R 5 , —S(O) 2 R 6 , or —S(O) 2 NR 4 R 5 ; or

R 3 is C 1 –C 6 alkylene or C 1 –C 6 alkylene substituted with oxo, and is linked together with the nitrogen to which it is attached and to one of the benzimidazole nitrogens to form a heterocylic compound fused to the benzimidazole;

R, R′, and R″, are each independently selected from C 1 –C 6 alkylene, arylene, heteroarylene, C 3 –C 7 cycloalkylene, or heterocyclylene;

R′″ is C 1 –C 6 alkyl, aryl, heteroaryl, aralkyl, C 3 –C 7 cycloalkyl, or heterocyclic;

R 4 and R 5 are each independently selected from hydrogen, C 1 –C 6 alkyl, C 1 –C 6 haloalkyl, C 1 –C 6 alkylsulfanyl, C 1 –C 6 alkylsulfenyl, C 1 –C 6 alkylsulfonyl, aryl, heteroaryl, aralkyl, heterocyclic, C 3 –C 7 cycloalkyl, —C(O)OR 6 , —C(O)NR′″R′″, —C(O)NR′″H, —C(O)NH 2 , or —S(O) 2 NR′″R′″;

R 6 is hydrogen, C 1 –C 6 alkyl, C 1 –C 6 haloalkyl, aryl, heteroaryl, aralkyl, heterocyclic, or C 3 –C 7 cycloalkyl;

R 7 is hydrogen, C 1 –C 6 alkyl, —S(O) 2 R 6 , —RNR 4 R 5 , —RR 6 , or aralkyl; and

R 8 is hydrogen or halogen.

2. A compound as claimed in claim 1 , wherein the compound of formula (I) is a compound of formula (IV):

wherein E is, heteroaryl substituted with R 1 , or heteroaryl substituted with R 1 and R 2 , or a salt or solvate thereof.

3. A compound as claimed in claim 1 , wherein the group A is linked to the side chain —NHC(Z)NHE and to the linker group X of the benzimidazole core through a (-1,3-) or a (-1,4-) linkage.

4. A compound as claimed in claim 1 , wherein R 1 is C 1 –C 6 alkyl, aryloxy, C 1 –C 6 alkoxy, C 1 –C 6 haloalkyl, C 1 –C 6 haloalkylsulfanyl, C 1 –C 6 alkylsulfanyl, —C(O)OR 6 , halogen, —CN, or —NO 2 .

5. A compound as claimed in claim 1 , wherein R 2 is hydrogen, halogen, C 1 –C 6 alkyl, C 1 –C 6 alkoxy, or C 1 –C 6 haloalkyl.

6. A compound as claimed in claim 1 , wherein D is CH, T is CR 8 , M is C and Q is N(R 7 ) p , wherein p is 0, q is 1, R 7 is hydrogen, methyl, or S(O) 2 R 6 .

7. A compound as claimed in claim 1 , wherein D is CH, T is CR 8 , wherein R 8 is hydrogen or —Br, M is C and Q is N(R 7 ) p , wherein p is 1, q is 0, R 7 is hydrogen, methyl, —S(O) 2 R 6 , —RNR 4 R 5 , —RR 6 or aralkyl.

8. A compound as claimed in claim 1 , wherein D is CH, T is CR 8 , wherein R 8 is hydrogen, M is C and Q is N(R 7 ) p , wherein either p or q is 0, the other is 1 and R 7 is hydrogen.

9. A compound as claimed in claim 1 , wherein R 3 is —C(O) R 6 , —C(O)NR 4 R 5 , —C(O)OR 6 , —C(O)RO R 6 , —C(O)RC(O)OR 6 , —C(O)ROR′OR″OR 6 , —C(O)ROR′OR 6 , —C(O)RNR 4 R 5 , —C(O)RNR 4 C(O)R 6 , —C(O)RNR 4 C(O)OR 6 , —SO 2 R 6 , or —SO 2 NR 4 R 5 .

10. A compound as claimed in claim 1 , wherein A is phenyl; X is O; Z is O; R 1 is C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 haloalkyl, or —NO 2 ; R 2 is hydrogen, halogen, C 1 –C 6 alkyl, or C 1 –C 6 alkoxy; and R 3 is —C(O)R 6 , —C(O)NR 4 R 5 , —C(O)OR 6 , —C(O)ROR 6 , —C(O)RC(O)OR 6 , —C(O)ROR′OR″OR 6 , —C(O)ROR′OR 6 , —C(O)RNR 4 R 5 , —C(O)RNR 4 C(O)R 6 , —C(O)RNR 4 C(O)OR 6 , —SO 2 R 6 , or —SO 2 NR 4 R 5 .

11. A compound as claimed in claim 1 , wherein A is phenyl; X is S; Z is O; R 1 is C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 haloalkyl, or —NO 2 ; R 2 is hydrogen, halogen, C 1 –C 6 alkyl, or C 1 –C 6 alkoxy; and R 3 is —C(O)R 6 , —C(O)NR 4 R 5 , —C(O)OR 6 , —C(O)ROR 6 , —C(O)RC(O)OR 6 , —C(O)ROR′OR″OR 6 , —C(O)ROR′OR 6 , —C(O)RNR 4 R 5 , —C(O)RNR 4 C(O)R 6 , —C(O)RNR 4 C(O)OR 6 , —SO 2 R 6 , or —SO 2 NR 4 R 5 .

12. A compound as claimed in claim 1 , wherein A is pyridyl; X is O; Z is O; R 1 is C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 haloalkyl, or —NO 2 ; R 2 is hydrogen, halogen, C 1 –C 6 alkyl, or C 1 –C 6 alkoxy; and R 3 is —C(O)R 6 , —C(O)NR 4 R 5 , —C(O)OR 6 , —C(O)ROR 6 , —C(O)RC(O)OR 6 , —C(O)ROR′OR″OR 6 , —C(O)ROR′OR 6 , —C(O)RNR 4 R 5 , —C(O)RNR 4 C(O)R 6 , —C(O)RNR 4 C(O)OR 6 , —SO 2 R 6 , or —SO 2 NR 4 R 5 .

13. A compound as claimed in claim 1 , wherein A is pyridyl; X is S; Z is O; R 1 is C 1-6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 haloalkyl, or —NO 2 ; R 2 is hydrogen, halogen, C 1 –C 6 alkyl, or C 1 –C 6 alkoxy; and R 3 is —C(O)R 6 , —C(O)NR 4 R 5 , —C(O)OR 6 , —C(O)ROR 6 , —C(O)RC(O)OR 6 , —C(O)ROR′OR″OR 6 , —C(O)ROR′OR 6 , —C(O)RNR 4 R 5 , —C(O)RNR 4 C(O)R 6 , —C(O)RNR 4 C(O)OR 6 , —SO 2 R 6 , or —SO 2 NR 4 R 5 .

14. A compound as claimed in claim 2 , wherein the compound is a compound of formula (IV) where E is heteroaryl substituted with R 1 , or heteroaryl substituted with R 1 and R 2 ; A is phenyl; X is O; Z is O; R 1 is C 1 –C 6 alkyl, aryl, C 3 –C 7 cycloalkyl, heterocyclyl, C 1 –C 6 haloalkyl, or C 1 –C 6 alkylsulfanyl; R 2 is hydrogen, halogen, C 1 –C 6 alkyl, or C 1 –C 6 haloalkyl; and R 3 is —C(O)R, —C(O)NR 4 R 5 , —C(O)OR 6 , —C(O)ROR 6 , —C(O)RC(O)OR 6 , —C(O)ROR′OR″OR 6 , —C(O)ROR′OR 6 , —C(O)RNR 4 R 5 , —C(O)RNR 4 C(O)R 6 , —C(O)RNR 4 C(O)OR 6 , —SO 2 R 6 , or —SO 2 NR 4 R 5 .

15. A compound as claimed in claim 1 , selected from the group consisting of:

methyl N-(5-(4-((5-tert-butylisoxazole-3-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)carbamate;

methyl N-(5-(3-((5-tert-butylisoxazole-3-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)carbamate;

methyl N-(5-(4-((5-tert-butylisoxazole-3-yl)aminocarbonylamino)phenylthio)-1H-benzimidazol-2-yl)carbamate;

methyl N-(5-(3-((3-phenyl-1,2,4-thiadiazol-5-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)carbamate;

N-(5-(4-((5-methylisoxazol-3-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((thiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((4-methylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((5-methylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((5-methyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((5-ethyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((5-cyclopropyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((4-tert-butylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((5-tert-butyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((4,5-dimethylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((5-morpholino-1,3,4-triazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((5-methylisoxazol-3-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((thiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((4-methylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((5-methylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((5-methyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((5-ethyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((5-cyclopropyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((4tert-butylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((5-tert-butyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((5-ethylthio-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((5-propylthio-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((4,5-dimetylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((5-morpholino-1,3,4-triazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide;

N-(5-(4-((5-methylisoxazol-3-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((thiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((4-methylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((5-methylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((5-methyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-fury)formamide;

N-(5-(4-((5-ethyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((5-cycloproyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((4-tert-butylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((5-tert-butyl-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((5-ethylthio-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((4,5-dimethylthiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((5-morpholino-1,3,4-triazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

N-(5-(4-((5-methylthio-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)acetamide;

N-(5-(4-((5-methylthio-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-(methoxy)ethoxy)acetamide; and

N-(5-(4-((5-methylthio-1,3,4-thiadiazol-2-yl)aminocarbonylamino)phenoxy)-1H-benzimidazol-2-yl)(2-furyl)formamide;

or a salt or solvate thereof.

16. A pharmaceutical composition, comprising: a therapeutically effective amount of a compound as claimed in claim 1 , or a salt or solvate, thereof and one or more of pharmaceutically acceptable carriers, diluents and excipients.

17. A pharmaceutical composition, comprising: a therapeutically effective amount of a compound as claimed in claim 2 , or a salt or solvate thereof and one or more of pharmaceutically acceptable carriers, diluents and excipients.

18. A pharmaceutical composition, comprising: a therapeutically effective amount of a compound as claimed in claim 15 , or a salt or solvate thereof and one or more of pharmaceutically acceptable carriers, diluents and excipients.