Functionalized NANOLUC inhibitors

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

wherein:

A is absent, an optionally substituted phenyl ring, or an optionally substituted thienyl ring,

L 1 is —(CR a1 R a2 ) m1 —, wherein m is 1 to 100, optionally wherein one or more CR a1 R a2 groups are replaced by a heteroatom or heteroatom group selected from the group consisting of O, N(R a3 ), S(═O), and S(═O) 2 , optionally wherein one or more CR a1 R a2 groups are replaced by C(═O), optionally wherein two adjacent CR a1 R a2 groups form CR a1 ═CR a1 , and optionally wherein one or more CR a1 R a2 groups are replaced by a -Cy- group, wherein each Cy is independently selected from the group consisting of aryl, heteroaryl, cycloalkyl, cycloalkenyl, and heterocycle; wherein R a1 , R a2 , and R a3 are independently selected from the group consisting of hydrogen and C 1 -C 4 -alkyl;

Z is C 1 -C 10 haloalkyl, a leaving group Y, a bioactive agent, or a dye, wherein the leaving group Y is selected from the group consisting of OR 4 , halogen, heteroaryl, and heterocyclyl;

R 1 is hydrogen or C 1 -C 8 alkyl;

R 2 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 3 is hydrogen or C 1 -C 8 alkyl; and

R 4 is selected from the group consisting of 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.

2. The compound of claim 1 , or a salt thereof, wherein A is an optionally substituted phenyl ring.

3. The compound of claim 1 , or a salt thereof, wherein A is an optionally substituted thienyl ring.

4. The compound of claim 1 , or a salt thereof, wherein R 1 is selected from the group consisting of hydrogen, C 1 -C 8 alkyl, halo-C 1 -C 8 -alkyl, alkoxyalkoxyalkyl and arylalkyl.

5. The compound of claim 1 , or a salt thereof, wherein R 2 is optionally substituted aryl.

6. The compound of claim 1 , or a salt thereof, wherein R 2 is phenyl substituted with at least one substituent selected from the group consisting of C 1 -C 4 alkyl, cyano, amido, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, and hydroxyalkyl.

7. The compound of claim 1 , or a salt thereof, wherein R 3 is hydrogen.

8. The compound of claim 1 , or a salt thereof, wherein the compound has formula (Ia):

wherein:

A is absent, a phenyl ring, or a thienyl ring;

R 2 is phenyl substituted with at least one C 1 -C 4 alkyl or C 1 -C 4 haloalkyl; and

L 2 is —(CR a1 R a2 ) m2 —, wherein m2 is 1 to 90, and wherein each CR a1 R a2 is as defined in claim 1 .

9. The compound of claim 1 , or a salt thereof, wherein the compound has formula (Ib):

wherein:

A is absent, a phenyl ring, or a thienyl ring;

R 2 is phenyl substituted with at least one C 1 -C 4 alkyl or C 1 -C 4 haloalkyl;

R x and R y at each occurrence is independently hydrogen or C 1 -C 4 alkyl;

p is 4, 5, 6, 7, 8, 9, or 10;

t is 0 or 1;

v is 0 or 1; and

L 3 is absent or —(CR a1 R a2 ) m3 —, wherein m3 is 1 to 80, and wherein each CR a1 R a2 is as defined in claim 1 .

10. The compound of claim 9 , or a salt thereof, wherein L 3 is —(CR a1 R a2 ) m3 —, wherein m3 is 1-20, and R a1 and R a2 , at each occurrence are independently hydrogen or C 1 -C 4 alkyl.

11. The compound of claim 9 , or a salt thereof, wherein L 3 is -Q 1 -(CH 2 —CH 2 —O) k1 -Q 2 -(CH 2 —CH 2 —O) k2 -Q 3 -(CH 2 —CH 2 —O) k3 —, wherein:

Q 1 is absent, O, or NH;

Q 2 is absent,

—CO—NH—, —CH 2 —CH 2 —CO—, —CH 2 —CH 2 —NH—CO, or —CH 2 —CH 2 —CO—NH—

Q 3 is absent, —CO—NH—, or —CH 2 —CH 2 —;

k1 is 1-10;

k2 is 0-10; and

k3 is 0-10.

12. The compound of claim 9 , or a salt thereof, wherein L 3 is selected from the group consisting of:

13. The compound of claim 1 , or a salt thereof, wherein Z is C 1 -C 10 haloalkyl.

14. The compound of claim 13 , or a salt thereof, wherein the compound has formula (Ic):

wherein:

A is a phenyl ring or thienyl ring;

R 2 is phenyl substituted with one methyl or ethyl group;

R x and R y at each occurrence is independently hydrogen or C 1 -C 4 alkyl;

p is 4, 5, 6, 7, 8, 9, or 10; and

L 3 is

15. The compound of claim 13 , or a salt thereof, wherein Z is —(CH 2 ) 6 —Cl.

16. The compound of claim 1 , or a salt thereof, wherein Z is a leaving group Y selected from the group consisting of OR 4 , halogen, heteroaryl, and heterocyclyl.

17. The compound of claim 16 , or a salt thereof, wherein the compound has formula (Id):

wherein:

A is a phenyl ring or a thienyl ring,

R 2 is phenyl substituted with one substituent selected from the group consisting of methyl, ethyl, —CH 2 Br, and —CH 2 CH 2 CH 2 Br;

R x and R y at each occurrence is independently hydrogen or C 1 -C 4 alkyl;

p is 4, 5, 6, 7, 8, 9, or 10;

t is 0 or 1;

v is 0 or 1; and

L 3 is absent, C 1 -C 4 alkylene,

18. The compound of claim 17 , or a salt thereof, wherein Z is chloro, bromo, iodo, C 1 -C 4 alkoxy, phenoxy,

19. The compound of claim 17 , or a salt thereof, wherein

L 3 is absent,

and

Z is C 1 -C 4 alkoxy, phenoxy,

20. The compound of claim 17 , or a salt thereof, wherein

L 3 is —CH 2 —CH 2 —, or

and Z is

or

L 3 is C 1 -C 4 alkylene; and Z is chloro, bromo, or iodo.

21. The compound of claim 17 , or a salt thereof wherein,

t is 0;

v is 0;

L 3 is absent; and

Z is bromo, iodo, or

22. The compound of claim 1 , or a salt thereof, wherein Z is a bioactive agent selected from the group consisting of an enzyme inhibitor, a receptor inhibitor, and a moiety which induces protein degradation.

23. The compound of claim 22 , or a salt thereof, wherein Z is a kinase inhibitor.

24. The compound of claim 22 , or a salt thereof, wherein the compound has formula (Ie):

wherein:

A is absent, a phenyl ring or a thienyl ring,

R 2 is phenyl substituted with one methyl or ethyl group;

R x and R y at each occurrence is independently hydrogen or C 1 -C 4 alkyl;

p is 4, 5, 6, 7, 8, 9, or 10;

L 3 is

and

Z is

and

Z is

25. The compound of claim 1 , or a salt thereof, wherein Z is a dye.

26. The compound of claim 25 , or a salt thereof, wherein the compound has formula (If′):

wherein:

A is a phenyl ring or thienyl ring;

R 2 is phenyl substituted with one methyl or ethyl group;

R x and R y at each occurrence is independently hydrogen or C 1 -C 4 alkyl;

p is 4, 5, 6, 7, 8, 9, or 10;

L 3 is absent,

and

Z is

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

1-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexyl)-1,10-dioxo-11,14,17-trioxa-2,9-diazanonadecan-19-yl (2-(2-((6-chlorohexyl)oxy)ethoxy)ethyl)carbamate;

[(E)-30-chloro-6,17-dioxo-5,10,13,16,21,24-hexaoxa-7,18-diazatriacont-2-en-1-yl (1-(trans-4-(4-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexyl)-1,10-dioxo-11,14,17-trioxa-2,9-diazanonadecan-19-yl)carbamate;

[(E)-30-chloro-6,17-dioxo-5,10,13,16,21,24-hexaoxa-7,18-diazatriacont-2-en-1-yl (1-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexyl)-1,10-dioxo-11,14,17-trioxa-2,9-diazanonadecan-19-yl)carbamate;

1-(trans-4-(4-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexyl)-1,10-dioxo-11,14,17-trioxa-2,9-diazanonadecan-19-yl (2-(2-((6-chlorohexyl)oxy)ethoxy)ethyl)carbamate;

1-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexyl)-1,10-dioxo-11,14,17-trioxa-2,9-diazanonadecan-19-yl (2-(2-((6-chlorohexyl)oxy)ethoxy)ethyl)carbamate;

2,5-dioxopyrrolidin-1-yl 1-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexyl)-1,8-dioxo-12,15-dioxa-2,9-diazaoctadecan-18-oate;

2,5-dioxopyrrolidin-1-yl 1-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexyl)-1,8-dioxo-12,15,18-trioxa-2,9-diazahenicosan-21-oate;

2,5-dioxopyrrolidin-1-yl 1-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexyl)-1,8-dioxo-12,15,18,21-tetraoxa-2,9-diazatetracosan-24-oate;

2,5-dioxopyrrolidin-1-yl 1-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexyl)-1,10-dioxo-14,17-dioxa-2,11-diazaicosan-20-oate;

2,5-dioxopyrrolidin-1-yl 1-((1r,4r)-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexyl)-1,10-dioxo-14,17,20-trioxa-2,11-diazatricosan-23-oate;

2,5-dioxopyrrolidin-1-yl 1-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexyl)-1,10-dioxo-14,17,20,23-tetraoxa-2,11-diazahexacosan-26-oate;

2,5-dioxopyrrolidin-1-yl 1-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexyl)-1,8-dioxo-12,15,18,21,24,27,30,33-octaoxa-2,9-diazahexatriacontan-36-oate;

N-(trans-4-((6-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)hexyl)carbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-(trans-4-((1-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-3,13-dioxo-7,10-dioxa-4,14-diazaicosan-20-yl)carbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

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

methyl 8-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexane-1-carboxamido)octanoate;

methyl 6-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-14H-indole-2-carboxamido)cyclohexane-1-carboxamido)hexanoate;

2,5-dioxopyrrolidin-1-yl 8-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexane-1-carboxamido)octanoate;

2,5-dioxopyrrolidin-1-yl 6-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexane-1-carboxamido)hexanoate;

phenyl 8-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexane-1-carboxamido)octanoate;

phenyl 6-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexane-1-carboxamido)hexanoate;

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

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

1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-N-(trans-4-((8-iodooctyl)carbamoyl)cyclohexyl)-1H-indole-2-carboxamide;

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

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

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

sodium 1-((8-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)octanoyl)oxy)-2,5-dioxopyrrolidine-3-sulfonate;

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

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

2,3,5,6-tetrafluorophenyl 8-(trans-4-(4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamido)cyclohexane-1-carboxamido)octanoate;

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

N-(trans-4-((1-(4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)piperazin-1-yl)-7,17-dioxo-3,10,13-trioxa-6,16-diazadocosan-22-yl)carbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-(2-chloro-6-methylphenyl)-2-((6-(4-(1-(trans-4-(1-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-1H-pyrrole-2-carboxamido)cyclohexyl)-1,8,18-trioxo-12,15,22-trioxa-2,9,19-triazatetracosan-24-yl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide;

N-(trans-4-((1-(4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)piperazin-1-yl)-7,17-dioxo-3,10,13-trioxa-6,16-diazadocosan-22-yl)carbamoyl)cyclohexyl)-4-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-(2-chloro-6-methylphenyl)-2-((6-(4-(1-(trans-4-(1-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-1H-pyrrole-2-carboxamido)cyclohexyl)-1,8,24-trioxo-12,15,18,21,28-pentaoxa-2,9,25-triazatriacontan-30-yl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide;

N-(trans-4-((1-(4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)piperazin-1-yl)-7,23-dioxo-3,10,13,16,19-pentaoxa-6,22-diazaoctacosan-28-yl)carbamoyl)cyclohexyl)-4-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

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

5-((6-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexane-1-carboxamido)hexyl)carbamoyl)-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-3′,6′-diyl diacetate;

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

N-(trans-4-((6-(3′,6′-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-6-carboxamido)hexyl)carbamoyl)cyclohexyl)-1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamide;

N-(trans-4-((6-(3′,6′-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-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-(3-(5,5-difluoro-7,9-dimethyl-5H-514,614-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-3-yl)propanamido)hexyl)carbamoyl)cyclohexyl)-1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamide;

N-(trans-4-((6-(3-(5,5-difluoro-7,9-dimethyl-5H-514,614-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-3-yl)propanamido)hexyl)carbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-(trans-4-((6-(3′,6′-diamino-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-5,6-carboxamido)hexyl)carbamoyl)cyclohexyl)-1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamide;

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

N-(trans-4-((8-(3′,6′-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-5-carboxamido)octyl)carbamoyl)cyclohexyl)-1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamide;

N-(trans-4-((8-(3′,6′-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-5-carboxamido)octyl)carbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-(trans-4-((8-(3′,6′-diamino-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-5,6-carboxamido)octyl)carbamoyl)cyclohexyl)-1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamide;

N-(trans-4-((8-(3′,6′-diamino-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-5-carboxamido)octyl)carbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5,6-carboxamide;

N-(trans-4-((8-(3-(5,5-difluoro-7,9-dimethyl-5H-5λ,6λ4-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-3-yl)propanamido)octyl)carbamoyl)cyclohexyl)-1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamide;

N-(trans-4-((8-(3-(5,5-difluoro-7,9-dimethyl-5H-5λ4,6λ4-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-3-yl)propanamido)octyl)carbamoyl)cyclohexyl)-4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

N-(trans-4-((1-(3′,6′-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthen]-6-yl)-1,11-dioxo-5,8-dioxa-2,12-diazaoctadecan-18-yl)carbamoyl)cyclohexyl)-1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamide;

N-(trans-4-((1-(3′,6′-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthen]-5,6-yl)-1,11-dioxo-5,8-dioxa-2,12-diazaicosan-20-yl)carbamoyl)cyclohexyl)-1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamide;

N-(trans-4-((1-(3′,6′-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthen]-6-yl)-1,11-dioxo-5,8-dioxa-2,12-diazaicosan-20-yl)carbamoyl)cyclohexyl)-1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamide;

N-(trans-4-((8-(6-((Z)-2-((E)-3-(1,1-dimethyl-1,4,5,6-tetrahydro-3λ4-pyrrolo[3,2,1-ij]quinolin-2-yl)allylidene)-1-methyl-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)hexanamido)octyl)carbamoyl)cyclohexyl)-1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamide;

N-(trans-4-((8-(4′,5′-dichloro-3′,6′-dihydroxy-2′,7′-dimethoxy-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-5,6-carboxamido)octyl)carbamoyl)cyclohexyl)-1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamide;

N1-(2-(5,5-difluoro-1,3-dimethyl-5H-5λ4,6λ4-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-10-yl)ethyl)-N4-(1-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexyl)-1,10-dioxo-13,16-dioxa-2,9-diazaoctadecan-18-yl)succinamide;

N1-(2-(5,5-difluoro-1,3-dimethyl-5H-5λ4,6λ4-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-10-yl)ethyl)-N4-(8-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexane-1-carboxamido)octyl)succinamide;

N1-(2-(5,5-difluoro-1,3-dimethyl-5H-5λ4,6λ4-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-10-yl)ethyl)-N4-(1-(trans-4-(1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-1H-indole-2-carboxamido)cyclohexyl)-1,12-dioxo-15,18-dioxa-2,11-diazaicosan-20-yl)succinamide;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(trans-4-((8-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)oxy)octyl)carbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(trans-4-((6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)oxy)hexyl)carbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-N-(trans-4-((8-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)oxy)octyl)carbamoyl)cyclohexyl)-1H-indole-2-carboxamide;

1-(2-(ethyl(3-ethylphenyl)amino)-2-oxoethyl)-N-(trans-4-((6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)oxy)hexyl)carbamoyl)cyclohexyl)-1H-indole-2-carboxamide;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(trans-4-(((R)-3-((3S,4R)-3-hydroxy-4-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)-2,2-dimethyl-5,18-dioxo-8,11,14-trioxa-4,17-diazatricosan-23-yl)carbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(trans-4-(((R)-3-((3S,4R)-3-hydroxy-4-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)-2,2-dimethyl-5,21-dioxo-8,11,14,17-tetraoxa-4,20-diazahexacosan-26-yl)carbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide;

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(trans-4-(((R)-3-((3S,4R)-3-hydroxy-4-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)-2,2-dimethyl-5,18-dioxo-8,11,14-trioxa-4,17-diazapentacosan-25-yl)carbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide; and

4-(2-(ethyl(m-tolyl)amino)-2-oxoethyl)-N-(trans-4-(((R)-3-((3S,4R)-3-hydroxy-4-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)-2,2-dimethyl-5,21-dioxo-8,11,14,17-tetraoxa-4,20-diazaoctacosan-28-yl)carbamoyl)cyclohexyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide,

or a salt thereof.

28. A method of inhibiting an Oplophorus -derived luciferase the method comprising contacting the Oplophorus -derived luciferase with a compound of claim 1 or a salt thereof.

29. The method of claim 28 , wherein the Oplophorus -derived luciferase comprises a polypeptide of the amino acid sequence of SEQ ID NO: 2.

30. 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 or a salt thereof; and

(b) detecting luminescence in the sample,

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

31. A method to detect an interaction between a first protein and a second protein in a sample, the method comprising:

(a) contacting a sample with a coelenterazine substrate and the compound of claim 1 or a salt thereof, wherein the sample comprises:

(i) a first polynucleotide encoding a first fusion protein, wherein the first fusion protein comprises a first fragment of an Oplophorus -derived luciferase and a first protein; and

(ii) a second polynucleotide encoding a second fusion protein, wherein the second fusion protein comprises a second fragment of the Oplophorus -derived luciferase and a second protein; and

(b) detecting luminescence in the sample,

wherein the detection of luminescence indicates an interaction between the first protein and the second protein.

32. The method of claim 31 , wherein when the first protein and second protein interact, the first fragment of the Oplophorus -derived luciferase and the second fragment of the Oplophorus -derived luciferase reconstitute a full-length enzyme capable of stably binding the coelenterazine substrate.

33. A method to detect an interaction between a first protein and a second protein in a sample, the method comprising:

(a) contacting a sample with a coelenterazine substrate and the compound of claim 1 or a salt thereof, wherein the sample comprises:

(i) a first polynucleotide encoding a first fusion protein, wherein the first fusion protein comprises an Oplophorus -derived luciferase and a first protein, wherein the Oplophorus -derived luciferase is a bioluminescent donor; and

(ii) a second polynucleotide encoding a second fusion protein, wherein the second fusion protein comprises a fluorescent acceptor molecule and a second protein;

(b) detecting bioluminescence resonance energy transfer (BRET) in the sample, indicating an interaction or close proximity of the bioluminescent donor and the fluorescence acceptor.

34. The method of claim 30 , wherein the coelenterazine substrate is a coelenterazine, coelenterazine derivatives, coelenterazine analogs, pro-coelenterazine, or quinone-masked coelenterazine.

35. A bioluminescence resonance energy transfer (BRET) system comprising: a first fusion protein including a first target protein and a bioluminescence donor molecule, wherein the bioluminescence donor molecule is an Oplophorus -derived luciferase; a second fusion protein including a second target protein and a fluorescent acceptor molecule; a coelenterazine substrate, and the compound of claim 1 or a salt thereof.

36. A kit comprising:

(a) a compound of claim 1 or a salt thereof; and

(b) an Oplophorus -derived luciferase.

37. The kit of claim 36 , wherein the Oplophorus -derived luciferase comprises a polypeptide sequence of SEQ ID NO: 2.

38. The kit of claim 36 , further comprising a coelenterazine substrate.

39. A method to detect an interaction between a molecule of interest and a target protein in a sample, the method comprising:

(a) detecting a first bioluminescence resonance energy transfer (BRET) signal in a sample, the sample comprising:

(i) a polynucleotide encoding a fusion protein, the fusion protein comprising an Oplophorus -derived luciferase and a target protein, wherein the Oplophorus -derived luciferase is a bioluminescent donor;

(ii) a coelenterazine substrate;

(iii) the compound of claim 1 or a salt thereof; and

(iv) a fluorescent tracer comprising a fluorescent acceptor molecule and a ligand that binds to the target protein;

(b) contacting the sample with a molecule of interest; and

(c) detecting a second BRET signal in the sample, wherein a decrease in the second BRET signal compared to the first BRET signal indicates an interaction between the molecule of interest and the target protein.

40. A bioluminescence resonance energy transfer (BRET) system comprising: a fusion protein including a target protein and a bioluminescence donor molecule, wherein the bioluminescence donor molecule is an Oplophorus -derived luciferase; a fluorescent tracer comprising a fluorescent acceptor molecule and a ligand that binds to the target protein; a coelenterazine substrate, and the compound of claim 1 or a salt thereof.