Thienopyrrole compounds and uses thereof

1. A compound of formula (I), or a salt thereof:

wherein:

the dashed line represents the presence or absence of a bond;

n is 0, 1, 2, 3, 4 or 5;

X is CH, N, O, or S;

wherein, when the dashed line represents the presence of a bond, X is CH or N, and

when the dashed line represents the absence of a bond, X is O or S;

A is an optionally substituted phenyl ring, or an optionally substituted 5- or 6-membered heteroaryl ring;

R 1 is selected from the group consisting of hydrogen, optionally substituted C 1 -C 8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted alkoxyalkyl and optionally substituted alkoxyalkoxyalkyl;

R 2 is optionally substituted aryl; and

R 3 and R 4 are each independently selected from the group consisting of hydrogen, optionally substituted C 1 -C 8 alkyl, optionally substituted C 3 -C 8 -cycloalkyl, optionally substituted C 3 -C 8 -cycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, or R 3 and R 4 , together with the nitrogen atom to which they are attached, together form an optionally substituted ring.

2. The compound of claim 1 , wherein n is 1.

3. The compound of claim 1 , wherein the dashed line represents the presence of a bond, and X is CH.

4. The compound of claim 1 , wherein A is a 5-membered heteroaryl ring.

5. The compound of claim 1 , wherein A is a thienyl ring, a furanyl ring, or a phenyl ring.

6. The compound of claim 1 , wherein R 1 is selected from the group consisting of C 1 -C 8 alkyl, halo-C 1 -C 8 -alkyl, alkoxyalkoxyalkyl and arylalkyl.

7. The compound of claim 1 , wherein R 3 and R 4 , together with the nitrogen atom to which they are attached, together form an optionally substituted ring.

8. The compound of claim 1 , wherein R 3 is hydrogen.

9. The compound of claim 1 , wherein R 4 is selected from the group consisting of unsubstituted C 1 -C 8 alkyl, halo-C 1 -C 8 alkyl, carboxy-C 1 -C 8 -alkyl, C 1 -C 4 -alkoxycarbonyl-C 1 -C 8 alkyl, optionally substituted phenyl, optionally substituted C 5 -C 6 cycloalkyl, optionally substituted C 5 -C 6 -cycloalkylalkyl, optionally substituted heteroarylalkyl.

10. The compound of claim 1 , wherein the compound has formula (Ia):

11. The compound of claim 1 , wherein the compound has formula (Ib):

wherein:

Y is selected from the group consisting of —NR a R b and —OR c ;

R a and R b are each independently selected from the group consisting of hydrogen, optionally substituted C 1 -C 8 alkyl, optionally substituted C 3 -C 8 -cycloalkyl, and optionally substituted heterocyclyl; or R a and R b , together with the nitrogen atom to which they are attached, together form an optionally substituted ring; and

R c is selected from the group consisting of hydrogen and optionally substituted C 1 -C 4 alkyl.

12. The compound of claim 11 , wherein the compound has the following formula (Ib′)

13. The compound of claim 1 , wherein the compound is selected from the group consisting of:

N-cyclohexyl-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-ethyl-2-(5-(pyrrolidine-1-carbonyl)-4H-thieno[3,2-b]pyrrol-4-yl)-N-(m-tolyl)acetamide;

N-ethyl-2-(5-(piperidine-1-carbonyl)-4H-thieno[3,2-b]pyrrol-4-yl)-N-(m-tolyl) acetamide;

ethyl 1-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl)piperidine-4-carboxylate;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-phenyl-4H-thieno[3,2-b]pyrrole-5-carboxamide;

ethyl 2-(4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)phenyl)acetate;

methyl 3-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)benzoate;

methyl-cis-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

8-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)octanoic acid;

6-(4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)piperidin-1-yl)-6-oxohexanoic acid;

trans-methyl-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylic acid;

N-(trans-4-(butylcarbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(trans-4-((2-hydroxyethyl)carbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-(trans-4-((2-(dimethylamino)ethyl)carbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

4-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)butanoic acid;

N-(trans-4-carbamoylcyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(trans-4-(hexylcarbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

ethyl 1-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carbonyl)piperidine-4-carboxylate;

methyl 6-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)hexanoate;

6-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)hexanoic acid;

1-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carbonyl)piperidine-4-carboxylic acid;

8-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)octanoic acid;

N-(trans-4-(cyclohexylcarbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(trans-4-((1-methylpiperidin-4-yl)carbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

tert-butyl 4-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)piperidine-1-carboxylate;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(trans-4-(piperidin-4-ylcarbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-(trans-4-((1-acetylpiperidin-4-yl)carbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

tert-butyl (6-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)hexyl)carbamate;

N-(trans-4-((6-(3′,6′-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-5(6)-carboxamido)hexyl)carbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-(trans-4-((6-aminohexyl)carbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide hydrochloride;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(trans-4-((6-hydroxyhexyl) carbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

methyl-trans-4-(trans-4-(4-(2-(ethcyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)cyclohexane-1-carboxylate;

trans-4-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)cyclohexane-1-carboxylic acid;

(11S,14S,17S)-17-acetamido-11,14-bis(carboxymethyl)-1-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexyl)-1,10,13,16-tetraoxo-2,9,12,15-tetraazanonadecan-19-oic acid;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-methyl-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-cyclopentyl-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(pyridin-4-ylmethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(3-morpholinopropyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-ethyl-2-(5-(4-methylpiperazine-1-carbonyl)-4H-thieno[3,2-b]pyrrol-4-yl)-N-(m-tolyl)acetamide;

N-cyclohexyl-4-(2-((2-(2-methoxyethoxy)ethyl)(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

methyl-trans-4-(4-(2-((2-(2-methoxyethoxy)ethyl)(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

N-cyclohexyl-4-(2-(hexyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

methyl-trans-4-(4-(2-(hexyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

6-(cis-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)hexanoic acid;

methyl 6-(trans-4-((4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)methyl)cyclohexane-1-carboxamido)hexanoate;

6-(trans-4-((4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)methyl)cyclohexane-1-carboxamido)hexanoic acid;

sodium 6-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)hexane-1-sulfonate;

potassium 6-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)hexane-1-sulfonate;

trans-4-(4-(2-(hexyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylic acid;

methyl trans-4-(4-(2-(ethyl(phenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-((3-cyanophenyl)(ethyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-((3-carbamoylphenyl)(ethyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-(ethyl(3-methoxyphenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-(ethyl(o-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-(6-methyl-3,4-dihydroquinolin-1 (2H)-yl)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-(ethyl(p-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-(ethyl(4-(hydroxymethyl)phenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(1-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(1-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-6-methoxy-1H-indole-2-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-furo[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

4-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-N-(trans-4-((6-hydroxyhexyl)carbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

sodium 6-(trans-4-(4-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)hexane-1-sulfonate;

methyl trans-4-(4-(2-(ethyl(3-isopropylphenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-(ethyl(3-(hydroxymethyl)phenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-((3-(bromomethyl)phenyl)(ethyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-((3-(dimethylamino)phenyl)(ethyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(4-(2-(ethyl(3-isobutylphenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate;

methyl trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexane-1-carboxylate;

1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-N-(trans-4-((6-hydroxyhexyl)carbamoyl)cyclohexyl)-1H-indole-2-carboxamide;

sodium 6-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexane-1-carboxamido)hexane-1-sulfonate; and

methyl trans-4-(6-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-6H-thieno[2,3-b]pyrrole-5-carboxamido)cyclohexane-1-carboxylate,

or salt thereof.

14. A method of inhibiting an Oplophorus -derived luciferase the method comprising contacting the Oplophorus -derived luciferase with a compound of claim 1 .

15. The method of claim 14 , wherein the Oplophorus -derived luciferase comprises a polypeptide sequence of SEQ ID NO: 2.

16. A method for modulating luminescence of an Oplophorus -derived luciferase in a sample, the method comprising,

(a) contacting the sample with a coelenterazine substrate and the compound of claim 1 ; and

(b) detecting luminescence in the sample,

wherein the compound of claim 1 causes a decrease in the luminescence from the Oplophorus -derived luciferase.

17. A compound of formula (I), or a salt thereof:

wherein:

the dashed line represents the presence or absence of a bond;

n is 0, 1, 2, 3, 4 or 5;

X is CH, N, O, or S;

wherein, when the dashed line represents the presence of a bond, X is CH or N, and

when the dashed line represents the absence of a bond, X is O or S;

A is an optionally substituted phenyl ring, or an optionally substituted 5or 6-membered heteroaryl ring;

R 1 is selected from the group consisting of hydrogen, optionally substituted C 1 -C 8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted alkoxyalkyl and optionally substituted alkoxyalkoxyalkyl;

R 2 is phenyl substituted with one substituent selected from the group consisting of C 1 -C 4 alkyl, cyano, amido, C 1 -C 4 alkoxy, and hydroxyalkyl; and

R 3 and R 4 are each independently selected from the group consisting of hydrogen, optionally substituted C 1 -C 8 alkyl, optionally substituted C 3 -C 8 -cycloalkyl, optionally substituted C 3 -C 8 -cycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclylalkyl; or R 3 and R 4 , together with the nitrogen atom to which they are attached, together form an optionally substituted ring.

18. The compound of claim 1 , wherein

n is 1;

the dashed line represents the presence of a bond, X is CH; and

A is an optionally substituted phenyl ring.

19. The compound of claim 18 , wherein R 1 is C 1 -C 8 alkyl.

20. The compound of claim 19 , wherein R 2 is optionally substituted phenyl.

21. The compound of claim 20 , wherein R 4 is optionally substituted C 3 -C 8 cycloalkyl.

22. The compound of claim 1 , wherein

n is 1;

the dashed line represents the presence of a bond, X is CH; and

A is a thienyl ring or a furanyl ring.

23. The compound of claim 22 , wherein R 1 is C 1 -C 8 alkyl.

24. The compound of claim 23 , wherein R 2 is optionally substituted phenyl.

25. The compound of claim 1 , which is sodium 6-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)hexane-1-sulfonate.