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US 2015/0309041 A1Published application
Reactive labelling compounds and uses thereof
AssigneeAcademia Sinica
InventorsChi-Huey WONG, Jim-Min FANG, Jiun-Jie SHIE
Life of this patent
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Abstract
Provided are azido-BODIPY compounds of formula (I), cyclooctyne-based fluorogenic probes of formula (IV), and activity-based probes of formula (VI). These compounds undergo azide alkyne cycloadditions (AAC) with to form triazolyl products. The provided compounds are useful for detection and imaging of alkyne-, or azide-containing molecules. Methods for detection and imaging biomolecules using compounds of the present disclosure are disclosed.
Claims46
A compound of Formula (I):
- or a pharmaceutically acceptable salt, solvate, or hydrate thereof,
- wherein:
- each instance of G1, G2, G3, G5, G6, G7 and G8 is independently hydrogen, optionally substituted C1-6 alkyl, optionally substituted C1-6 alkenyl, optionally substituted C1-6 alkynyl, optionally substituted aryl, optionally substituted acyl, —ORA, —CH2ORA, —OC(O)RA, —SRA, —N(RB)2, —N(RA)C(O)RA, —C(O)N(RB)2, —CN, —NO2, —C(O)RA, —C(O)ORA, —S(O)RA, —SO2RA, —SO3RA, —SO2N(RB)2, and —NHSO2RB;
- each instance of R is independently selected from hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted acyl, —ORA, —CH2ORA, —OC(O)RA, —SRA, —N(RB)2, —N(RA)C(O)RA, —C(O)N(RB)2, —CN, —NO2, —C(O)RA, —C(O)ORA, S(O)RA, —SO2RA, —SO3RA, —SO2N(RB)2, and —NHSO2RB;
- each RA is independently selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocyclyl, and optionally substituted aryl;
- and
- each RB is independently selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocyclyl, and optionally substituted aryl, or two RB taken together with the intervening nitrogen form a heterocycle,
- each instance of G4a and G4b is fluoro, alkyl, alkoxy, aryloxy, or alkynyl, and
- wherein alkyl and alkoxy groups are unbranched, saturated, and have 1-4 carbon atoms;
- aryl groups and aryl groups of aryloxy can be either carbocyclic aryl or heterocyclic aryl;
- carbocyclic aryl groups have a total of 6-20 carbon atoms, including carbon atoms of substituents;
- heterocyclic aryl groups have a total of 5-20 carbon atoms, including carbon atoms of substituents;
- carboalkoxy groups are alkyl esters of a carboxylic acid wherein alkyl groups are as defined above;
- each alkyl, aryl, alkoxy, aryloxy, benzo, and carboalkoxy, independently, may be unsubstituted or substituted with one or more substituent;
- alkyl substituents are halo, hydroxyl, amino, or aryl;
- aryl substituents are halo, hydroxyl, amino, alkyl, aryl, nitro, or carboxyl;
- and halo substituents are fluoro or chloro;
- n is 0, 1, 2, 3, or 4.
15 more elements
A compound of formula (IV):
- or a pharmaceutically acceptable salt, solvate, or hydrate thereof, and wherein:
- each instance of G9, G10, G11, G12, G13, G14, G15, G16, G17 and G18 is independently hydrogen, optionally substituted C1-6 alkyl, optionally substituted C1-6 alkenyl, optionally halogen, optionally nitroso, optionally substituted C1-6 alkynyl, optionally substituted aryl, optionally substituted acyl, —ORA, —CH2ORA, —OC(O)RA, —SRA, —N(RB)2, —N(RA)C(O)RA, —C(O)N(RB)2, —CN, —NO2, —C(O)RA, —C(O)ORA, —S(O)RA, —SO2RA, —SO3RA, —SO2N(RB)2, and —NHSO2RB;
- each instance of R is independently selected from hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted acyl, —ORA, —CH2ORA, —OC(O)RA, —SRA, —N(RB)2, —N(RA)C(O)RA, —C(O)N(RB)2, —CN, —NO2, —C(O)RA, —C(O)ORA, S(O)RA, —SO2RA, —SO3RA, —SO2N(RB)2, and —NHSO2RB;
- each RA is independently selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocyclyl, and optionally substituted aryl;
- and
- each RB is independently selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocyclyl, and optionally substituted aryl, or two RB taken together with the intervening nitrogen form a heterocycle;
- each instance of G9 and G10 is hydrogen, fluoro, chloro, bromo, iodo, nitroso, alkyl, alkoxy, aryloxy, or alkynyl, and
- wherein alkyl and alkoxy groups are unbranched, saturated, and have 1-4 carbon atoms;
- aryl groups and aryl groups of aryloxy can be either carbocyclic aryl or heterocyclic aryl;
- carbocyclic aryl groups have a total of 6-20 carbon atoms, including carbon atoms of substituents;
- heterocyclic aryl groups have a total of 5-20 carbon atoms, including carbon atoms of substituents;
- carboalkoxy groups are alkyl esters of a carboxylic acid wherein alkyl groups are as defined above;
- each alkyl, aryl, alkoxy, aryloxy, benzo, and carboalkoxy, independently, may be unsubstituted or substituted with one or more substituent;
- alkyl substituents are halo, hydroxyl, amino, or aryl;
- aryl substituents are halo, hydroxyl, amino, alkyl, aryl, nitro, or carboxyl;
- and halo substituents are fluoro or chloro;
- and
- m is 0 or 1.
15 more elements
A compound of formula (V):
- wherein L is selected from the group consisting of F, Cl, Br, I, umbelliferyl, coumarin oxide, triflate, mesylate, tosylate, halogen, alkoxy, phenoxy, benzoate, pentafluorophenoxy, or 4-nitrophenoxy.
A compound of formula (VI):
- wherein L is selected from the group consisting of
- halogen, F, Cl, Br, I, alkoxy, phenoxy, pentafluorophenoxy, 4-nitrophenoxy, umbelliferyl, coumarin oxide, alkanoate, benzoate, triflate, mesylate, or tosylate.
Dependencies are inferred from the claim text.