Back to results
US 2017/0045496 A1Published application
Carbopyronone compounds useful as diagnostic adjuvants
AssigneeLife Technologies Corporation
InventorsKyle GEE, Hee Chol KANG, Wenjun ZHOU, Bradley DUBBELS, Michael OLSZOWY, Michael O'GRADY
Life of this patent
Estimating the term…
Abstract
Described herein are fluorescent compounds and methods and comprising these compounds. The compounds disclosed herein are carbopyronine reagents that fluoresce in the red portion of the UV/VIS spectrum and provide bright fluorescence intensity, uniform cell staining, and good retention within live cells as well as low toxicity toward cells.
Claims52
A compound of structural formula (I):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R14, R15, and R16 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-Sc;
- or
- R7 taken together with R14 are part of an optionally substituted 5- or 6-membered ring;
- R8 taken together with R15 are part of an optionally substituted 5- or 6-membered ring;
- R9 taken together with R11 are part of an optionally substituted 5- or 6-membered ring;
- R10 taken together with R16 are part of an optionally substituted 5- or 6-membered ring;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance.
9 more elements
A compound of structural formula (II):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R9, R11, R14, R17, R18, R19, R20, R21 and R22 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-Sc;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance.
4 more elements
A compound of structural formula (III):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R9, R11, R14, R17, R18, R19, R20, R21, R22, R23, and R24 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-Sc;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance.
4 more elements
A compound of structural formula (IV):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R9, R11, R14, R17, R18, R19, R20, R21, R22, R23, and R24 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-Sc;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance.
4 more elements
A compound selected from the group consisting of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25 and amine-reactive forms thereof.
The compound according to any of the preceding claims, wherein RX is an acrylamide, a carboxylic acid, an activated ester of a carboxylic acid, an acyl azide, an acyl halide, hydroxy, an aldehyde, an alkyl halide, a sulfonate, an amine, an anhydride, an aniline, an aryl halide, an azide, an aziridine, a boronate, a carbodiimide, a diazoalkane, an epoxide, a glycol, a haloacetamide, a halotriazine, a hydrazine, a hydroxylamine, an imido ester, an isothiocyanate, a ketone, a maleimide, a sulfonyl halide, or a thiol group.
The compound according to any of the preceding claims, wherein Sc is an amino acid, a peptide, a protein, a monosaccharide, a polysaccharide, an ion-complexing moiety, a nucleotide, an oligonucleotide, a nucleic acid, a hapten, a drug, a toxin, a lipid, a phospholipid, a lipoprotein, a lipopolysaccharide, a liposome, a lipophilic polymer, a PEG group, a non-biological organic polymer, a polymeric microparticle, an animal cell, a plant cell, a bacterium, a yeast, or a virus.
The compound according to any of the preceding claims, wherein Sc is a solid support.
A method for tracking cell proliferation, differentiation, and/or function, the method comprising the steps of:
- a) incubating a mixture of cells and a compound of structural formula (I):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R14, R15, and R16 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-Sc;
- or
- R7 taken together with R14 are part of an optionally substituted 5- or 6-membered ring;
- R8 taken together with R15 are part of an optionally substituted 5- or 6-membered ring;
- R9 taken together with R11 are part of an optionally substituted 5- or 6-membered ring;
- R10 taken together with R16 are part of an optionally substituted 5- or 6-membered ring;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance;
- b) providing a stimulus to the mixture to elicit a fluorescent signal;
- and
- c) analyzing the stimulated mixture.
13 more elements
A method for tracking cell proliferation, differentiation, and/or function, the method comprising the steps of:
- a) incubating a mixture of cells and a compound of structural formula (II):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R9, R11, R14, R17, R18, R19, R20, R21 and R22 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-S;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance;
- b) providing a stimulus to the mixture to elicit a fluorescent signal;
- and
- c) analyzing the stimulated mixture.
8 more elements
A method for tracking cell proliferation, differentiation, and/or function, the method comprising the steps of:
- a) incubating a mixture of cells and a compound of structural formula (III):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R9, R11, R14, R17, R18, R19, R20, R21, R22, R23, and R24 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-Sc;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance;
- b) providing a stimulus to the mixture to elicit a fluorescent signal;
- and
- c) analyzing the stimulated mixture.
8 more elements
A method for tracking cell proliferation, differentiation, and/or function, the method comprising the steps of:
- a) incubating a mixture of cells and a compound of structural formula (IV):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R9, R11, R14, R17, R18, R19, R20, R21, R22, R23, and R24 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-Sc;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance;
- b) providing a stimulus to the mixture to elicit a fluorescent signal;
- and
- c) analyzing the stimulated mixture.
8 more elements
A method for tracking cell proliferation, differentiation, and/or function, the method comprising the steps of:
- a) incubating a mixture of cells and a compound selected from the group consisting of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25 and amine-reactive forms thereof;
- b) providing a stimulus to the mixture to elicit a fluorescent signal;
- and
- c) analyzing the stimulated mixture.
1 more element
A kit for tracking cell proliferation, differentiation, and/or function, the kit comprising:
- a) a compound of structural formula (I):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R14, R15, and R16 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-Sc;
- or
- R7 taken together with R14 are part of an optionally substituted 5- or 6-membered ring;
- R8 taken together with R15 are part of an optionally substituted 5- or 6-membered ring;
- R9 taken together with R11 are part of an optionally substituted 5- or 6-membered ring;
- R10 taken together with R16 are part of an optionally substituted 5- or 6-membered ring;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance;
- b) an organic solvent;
- and
- c) a desiccant.
13 more elements
A kit for tracking cell proliferation, differentiation, and/or function, the kit comprising:
- a) a compound of structural formula (II):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R9, R11, R14, R17, R18, R19, R20, R21 and R22 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-Sc;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance;
- b) an organic solvent;
- and
- c) a desiccant.
8 more elements
A kit for tracking cell proliferation, differentiation, and/or function, the kit comprising:
- a) a compound of structural formula (III):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R9, R11, R14, R17, R18, R19, R20, R21, R22, R23, and R24 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-Sc;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance;
- b) an organic solvent;
- and
- c) a desiccant.
8 more elements
A kit for tracking cell proliferation, differentiation, and/or function, the kit comprising:
- a) a compound of structural formula (IV):
- or a pharmaceutically acceptable salt thereof, wherein
- R12 and R13 are each independently H, alkyl, substituted alkyl, -L-Rx, or -L-Sc;
- R2, R3, R4, R5, R6, R7, R9, R11, R14, R17, R18, R19, R20, R21, R22, R23, and R24 are each independently H, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester) amino, (carboxyl ester) oxy, cyano, alkylcarboxylate, hydroxyl, nitro, sulfo, sulfoalkyl, substituted sulfoalkyl, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthiol, substituted alkylthiol, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, -L-Rx, or -L-Sc;
- L is a linker;
- Rx is a reactive group;
- and
- Sc is a conjugated substance;
- b) an organic solvent;
- and
- c) a desiccant.
8 more elements
A kit for tracking cell proliferation, differentiation, and/or function, the kit comprising:
- a) a compound selected from the group consisting of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25 and amine-reactive forms thereof;
- b) an organic solvent;
- and
- c) a desiccant.
1 more element
A process for preparing a compound process for preparing a conjugated compound of structural formula (I), (II), (III) or (IV) the process comprising:
- reacting a compound of structural formula (I), (II), (III) or (IV) with a substance to be conjugated thereto, thereby resulting in a conjugated substance SC.
Dependencies are inferred from the claim text.