Thienopyrrole compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-2016376568-A1
Application number	US-201615192420-A
Country	US
Kind code	A1
Filing date	Jun 24, 2016
Priority date	Jun 25, 2015
Publication date	Dec 29, 2016
Grant date	—

Abstract

Thienopyrrole compounds that may inhibit Oplophorus -derived luciferases are disclosed, as well as compositions and kits comprising the thienopyrrole compounds, and methods of using the thienopyrrole compounds.

First claim

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 and R 2 are each independently 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; 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.

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 . (canceled)

7 . The compound of claim 1 , 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.

8 . (canceled)

9 . (canceled)

10 . The compound of claim 1 , wherein R 2 is optionally substituted aryl.

11 . (canceled)

12 . The compound of claim 1 , wherein 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.

13 . (canceled)

14 . 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.

15 . (canceled)

16 . (canceled)

17 . (canceled)

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

19 . 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 heterocyclyl, optionally substituted heteroarylalkyl, and optionally substituted heterocyclylalkyl.

20 . (canceled)

21 . (canceled)

22 . (canceled)

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

24 . 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 W 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.

25 .- 34 . (canceled)

35 . The compound of claim 24 , wherein the compound has the following formula (Ib′)

36 . 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)ami

Assignees

• Promega Corp

Inventors

• Duellman Sarah
• Robers Matthew B
• Walker Joel R
• Zhou Wenhui
• Zimprich Chad

Classifications

• G01N33/542

  with steric inhibition or signal modification, e.g. fluorescent quenching · CPC title

• G01N33/581

  with enzyme label (including co-enzymes, co-factors, enzyme inhibitors or substrates) · CPC title

• C07D493/04

  Ortho-condensed systems · CPC title

• C07K5/0222

  with the first amino acid being heterocyclic, e.g. Pro, Trp · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title