Back to results
US 2020/0063110 A1Published application
Thienopyrrole compounds and uses thereof
AssigneePromega Corporation
InventorsSarah Duellman, Matthew B. Robers, Joel R. Walker, Wenhui Zhou, Chad Zimprich
Life of this patent
Estimating the term…
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.
Claims68
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;
- R1 and R2 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted alkoxyalkyl and optionally substituted alkoxyalkoxyalkyl;
- and
- R3 and R4 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C3-C8-cycloalkyl, optionally substituted C3-C8-cycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclylalkyl;
- or R3 and R4, together with the nitrogen atom to which they are attached, together form an optionally substituted ring.
7 more elements
A method of inhibiting an Oplophorus-derived luciferase, the method comprising contacting the Oplophorus-derived luciferase with a compound of formula (II):
- 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;
- R1 and R2 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted alkoxyalkyl and optionally substituted alkoxyalkoxyalkyl;
- Z is selected from the group consisting of —NR3R4 and —OR5;
- and
- R3, R4 and R5 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C3-C8-cycloalkyl, optionally substituted C3-C8-cycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclylalkyl;
- or R3 and R4, together with the nitrogen atom to which they are attached, together form an optionally substituted ring.
8 more elements
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 a compound of formula (II):
- 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;
- R1 and R2 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted alkoxyalkyl and optionally substituted alkoxyalkoxyalkyl;
- Z is selected from the group consisting of —NR3R4 and —OR5;
- and
- R3, R4 and R5 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C3-C8-cycloalkyl, optionally substituted C3-C8-cycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclylalkyl;
- or R3 and R4, together with the nitrogen atom to which they are attached, together form an optionally substituted ring;
- and
- (b) detecting luminescence in the sample,
- wherein the compound of formula (II) causes a decrease in the luminescence from the Oplophorus-derived luciferase.
12 more elements
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 a compound of formula (II):
- 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;
- R1 and R2 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted alkoxyalkyl and optionally substituted alkoxyalkoxyalkyl;
- Z is selected from the group consisting of —NR3R4 and —OR5;
- and
- R3, R4 and R5 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C3-C8-cycloalkyl, optionally substituted C3-C8-cycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclylalkyl;
- or R3 and R4, together with the nitrogen atom to which they are attached, together form an optionally substituted ring,
- wherein the sample comprises:
- (xxi) 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
- (xxii) 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.
16 more elements
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 a compound of formula (II):
- 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;
- R1 and R2 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted alkoxyalkyl and optionally substituted alkoxyalkoxyalkyl;
- Z is selected from the group consisting of —NR3R4 and —OR5;
- and
- R3, R4 and R5 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C3-C8-cycloalkyl, optionally substituted C3-C8-cycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclylalkyl;
- or R3 and R4, together with the nitrogen atom to which they are attached, together form an optionally substituted ring,
- wherein the sample comprises:
- (xxiii) 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
- (xxiv) 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.
14 more elements
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 a compound formula (II):
- 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;
- R1 and R2 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted alkoxyalkyl and optionally substituted alkoxyalkoxyalkyl;
- Z is selected from the group consisting of —NR3R4 and —OR5;
- and
- R3, R4 and R5 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C3-C8-cycloalkyl, optionally substituted C3-C8-cy cl oal kyl al kyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclylalkyl;
- or R3 and R4, together with the nitrogen atom to which they are attached, together form an optionally substituted ring.
12 more elements
A kit comprising:
- (a) a compound of formula (II):
- 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;
- R1 and R2 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted alkoxyalkyl and optionally substituted alkoxyalkoxyalkyl;
- Z is selected from the group consisting of —NR3R4 and —OR5;
- and
- R3, R4 and R5 are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C3-C8-cycloalkyl, optionally substituted C3-C8-cycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclylalkyl;
- or R3 and R4, together with the nitrogen atom to which they are attached, together form an optionally substituted ring;
- and
- (b) an Oplophorus-derived luciferase.
11 more elements
Dependencies are inferred from the claim text.