NIR to SWIR fluorescent compounds for imaging and detection

Patent metadata

Field	Value
Publication number	US-11549017-B2
Application number	US-201816124639-A
Country	US
Kind code	B2
Filing date	Sep 7, 2018
Priority date	Sep 29, 2017
Publication date	Jan 10, 2023
Grant date	Jan 10, 2023

Abstract

This disclosure provides a family of compounds that absorb and fluoresce in the short wave infrared region (SWIR, optionally 1000 nm to 1300 nm), including hydrophilic compounds that exhibit absorption and emission spectral profiles in aqueous solutions substantially similar to those observed in organic solvents such as methanol or DMSO. The compounds can be chemically linked to biomolecules including proteins, nucleic acids, and therapeutic small molecules. The compounds are useful for imaging in a variety of medical, biological and diagnostic applications, including SWIR in vivo imaging of regions of interest within a mammal.

First claim

The invention claimed is:

1. A compound represented by the following structural formula:

or a salt thereof, wherein:
P 1 and P 2 are, independently, a substituted or unsubstituted acridine or acridinium moiety, a substituted or unsubstituted pyrylium or thiopyrylium moiety, or a benz[c,d]indole;
B is a substituted or unsubstituted polymethine, substituted or unsubstituted cyclic alkene or cyclic polyalkene, substituted or unsubstituted polycyclic alkene or polycyclic polyalkene, substituted or unsubstituted aryl or heteroaryl, substituted or unsubstituted alkenylaryl, thiadiazole, benzothiadiazole, or bisbenzothiadiazole;
L is absent or is a linker moiety, optionally bearing a functional group or reactive group selected from the group consisting of a carboxylate, carboxyalkyl, maleimide, succinimidyl ester, succinimidyl ester, carboxamide, propargyl, azidoalkyl, alkyne, isothiocyanate, of —NH 2 —OH, —SH, —SO 3 H, carboxyl, —COCl, —CONHNH 2 , acetoxymethyl esters, substituted and unsubstituted N-hydroxysuccinimidyl esters, substituted and unsubstituted N-hydroxysulfosuccinimido esters, nitro- or fluoro or phenol esters, azide, —COCH 2 I, phosphoramidite, phthalamido, acyl fluoride, acyl chloride, acyl azide, tyramide, cinnamamide, hydroxycinnamamide, aldehyde, ketone, phosphoramidite, isocyanate, isothiocyanate, sulfonyl chloride, maleimide, and biotin;
R is, independently for each occurrence, hydrogen, substituted or unsubstituted C 1 to C 24 alkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, sulfonate, aryl sulfonate, C 1 to C 24 alkyl sulfonate, taurine, carboxylate, amine, alkylamine, arylamine, alkylammonium, arylammonium, sulfonamide, halogen, hydroxy, amide, nitro, cyano, azide, O-alkyl, S-alkyl, silyl, trialkylsilyl, O-silyl, haloalkyl, alkylsulfhydryl, trifluoromethyl, hydrazide, substituted or unsubstituted aryl, heteroaryl, or heterocyclic alkynyl, carboxyalkyl, aminoalkyl, haloalkyl, azidoalkyl, amide, amino acid, peptide, or L, with the proviso that in at least one instance R in said compound comprises a sulfonate, aryl sulfonate, or C 1 to C 24 alkyl sulfonate;
wherein said compound comprises at least four sulfonates, alkyl sulfonates, arylsulfonates, taurines or a combination thereof, is water soluble, and absorbs and/or emits light between 950 nm and 1350 nm.

2. A compound represented by the following structural formula:

or a salt thereof, wherein:
P 1 and P 2 are a benz[c,d]indole moiety;
Q is a hydrogen, C 1 -C 24 alkyl, aryl, heteroaryl, polyaryl, phenyl, thienyl, furanyl, pyridyl, pyridinium, halogen, substituted or unsubstituted S-alkyl, substituted or unsubstituted S-aryl, substituted or unsubstituted O-alkyl, substituted or unsubstituted O-aryl, substituted or unsubstituted N-alkyl, substituted or unsubstituted N-aryl, cyano, trifluoromethyl, azidoaryl, boronic acid, boronic ester, hydroxyl, alkoxy, aryloxy, alkylthio, arylthio, nitrogen, silicon, boron, carboxy, cyano, ester, amine, amide, amino acid, peptide or L,
W is absent or a substituted or unsubstituted cyclic or polycyclic group containing aliphatic or aromatic carbon, nitrogen, oxygen, sulfur, or silicon forming a 4 to 9 membered ring;
L is absent or is a linker moiety, optionally bearing a functional group or reactive group, such as selected from the group consisting of a carboxylate, carboxyalkyl, maleimide, succinimidyl ester, carboxamide, propargyl, azidoalkyl, alkyne, isothiocyanate, of —NH 2 —OH, —SH, —SO 3 H, carboxyl, —COCl, —CONHNH 2 , acetoxymethyl esters, substituted and unsubstituted N-hydroxysuccinimidyl esters, substituted and unsubstituted N-hydroxysulfosuccinimido esters, nitro- or fluoro or phenol esters, azide, —COCH 2 I, phosphoramidite, phthalamido, acyl fluoride, acyl chloride, acyl azide, tyramide, cinnamamide, hydroxycinnamamide, aldehyde, ketone, phosphoramidite, isocyanate, isothiocyanate, sulfonyl chloride, maleimide and biotin;
R is, independently for each occurrence, hydrogen, substituted or unsubstituted C 1 to C 24 alkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, sulfonate, aryl sulfonate, C 1 to C 24 alkyl sulfonate, taurine, carboxylate, amine, alkylamine, arylamine, alkylammonium, arylammonium, sulfonamide, halogen, hydroxy, amide, nitro, cyano, azide, O-alkyl, S-alkyl, silyl, trialkylsilyl, O-silyl, haloalkyl, alkylsulfhydryl, trifluoromethyl, hydrazide, substituted or unsubstituted aryl, heteroaryl, or heterocyclic alkynyl, carboxyalkyl, aminoalkyl, haloalkyl, azidoalkyl, amide, amino acid, peptide or L, with the proviso that in at least one instance R in said compound comprises a sulfonate, aryl sulfonate, or C 1 to C 24 alkyl sulfonate;
x and y are, independently for each occurrence, integers from 0 to 15; and
wherein said compound comprises at least four sulfonates, alkyl sulfonates, arylsulfonates, taurines or a combination thereof, is water soluble, and absorbs and/or emits light between 950 nm and 1350 nm.

3. The compound of claim 1 , wherein the molecule absorbs and/or emits light between 1000 nm and 1250 nm.

4. The compound of claim 1 , wherein the optical absorbance and fluorescent emission properties are substantially similar in organic solvents, aqueous environments, and biological environments.

5. The compound of claim 1 , comprising a molecule selected from the group consisting of

and pharmaceutically acceptable salts thereof.

6. The compound of claim 1 , wherein P 1 and P 2 are a polysulfonated benz[c,d]indole.

7. The compound of claim 1 , wherein P 1 and P 2 are a polysulfonated thiopyrylium.

8. The compound of claim 1 , wherein P 1 and P 2 are a polysulfonated acridinium.

9. The compound of claim 1 , wherein the linking group, L, is bound, covalently or non-covalently, to biological material comprising a drug, peptide, protein, antibody, nucleic acid, carbohydrate, lipid, biomolecule, nanoparticle, membrane, cell or tissue.

10. A

Assignees

• Perkinelmer Health Sci Inc

Inventors

• Narayanan Nara
• Groves Kevin
• Ho Guojie

Classifications

• A61K49/0052

  Small organic molecules (oligomers, polymers, dendrimers A61K49/0054) · CPC title

• C07D333/74 Primary

  Naphthothiophenes · CPC title

• C07D333/50

  condensed with carbocyclic rings or ring systems · CPC title

• C07D403/14

  containing three or more hetero rings · CPC title

• C07D403/08

  linked by a carbon chain containing alicyclic rings · CPC title