Small tunable fluorophores for the detection and imaging of biomolecules

Patent metadata

Field	Value
Publication number	US-12415926-B2
Application number	US-202017439077-A
Country	US
Kind code	B2
Filing date	Mar 17, 2020
Priority date	Mar 18, 2019
Publication date	Sep 16, 2025
Grant date	Sep 16, 2025

Abstract

The invention relates to small, conjugatable, orthogonal and tunable fluorophores for imaging of small bioactive molecules. The invention further relates to processes for the preparation of the compounds, and uses of the compounds in therapeutic, diagnostic, surgery and analytical applications. The invention provides a compound of formula (I), a derivative or a salt thereof. Wherein X is selected from the group consisting of NH, O, S, SeR5R6, CR7R8; R1 is selected from the group consisting of amines, alcohols, thiols, thiophenols, selenols, selenophenols and aryl groups; R2 and R3 are independently H or a halogen; R4 tis either H, nitro or cyano; R5 is either absent or methyl or oxygen; R6 is either absent or methyl or oxygen; and R7 and R8 are independently selected from the group consisting of linear or cyclic alkyl groups containing halogen, amino, cyano or carboxylic ester substituents, and alkyl aryl groups.

First claim

The invention claimed is:

1. A compound of formula (I) or a salt thereof

wherein
X is NH or CR7R8;
R1 is selected from the group consisting of amines, alcohols, thiols, thiophenols, selenols, selenophenols and aryl groups;
R2 and R3 are independently H or a halogen;
R4 is nitro; and
R7 and R8 are independently selected from the group consisting of linear or cyclic alkyl groups containing halogen, amino, cyano or carboxylic ester substituents, and alkyl aryl groups.

2. The compound or a salt thereof according to claim 1 wherein X is CR7R8.

3. The compound or a salt thereof according to claim 1 wherein R1 is an amine.

4. The compound or a salt thereof according to claim 1 wherein R2 and/or R3 are/is H.

5. The compound or a salt thereof according to claim 1 wherein R7 and R8 are independently selected from the group consisting of linear alkyl, cyclic alkyl and aryl groups.

6. The compound according to claim 1 , which is selected from the group consisting of:

or a salt thereof.

7. The compound according to claim 6 , which is selected from the group consisting of:

or a salt thereof.

8. A process for the preparation of the compound derivative or a salt thereof according to claim 1 , said process comprising the step of:
a) providing an intermediate of formula II

wherein
R is a halogen atom;

R2 and R3 are independently H or a halogen; and
R4 is either H, nitro or cyano;

b) linking the two amino groups; and
c) performing a substitution reaction to replace the halogen with a nucleophile group.

9. A precursor compound of Formula (1a) or salt thereof

wherein X, R 2 , R 3 , R 4 are as defined as in claim 1 and R 1a is halogen.

10. A method of therapy, diagnosis, surgery, or analysis, the method comprising use of a compound or a salt thereof according to claim 1 .

11. The method according to claim 10 wherein the method is selected from the group consisting of optical coherence tomography, fluorescence spectroscopy, fluorimetry, fluorescence lifetime, fluorescence microscopy, fluorescence tomography, whole-body fluorescence imaging, flow cytometry, fluorescence-assisted cell sorting, fluorescence-guided surgery, fluorescence endomicroscopy, multi-spectral optoacoustic imaging, Raman spectroscopy, Raman imaging, fundus camera imaging and angiography.

12. The method according to claim 10 wherein the method comprises labelling, tracking, and/or imaging cells, tissues and organs in vivo, in vitro or ex vivo.

13. The method according to claim 10 , wherein the method is fluorescence-guided surgery of cancer or fluorescent probes for diagnosis of protein aggregates in neurodegenerative diseases.

Assignees

• Univ Court Univ Of Edinburgh

Inventors

• Vendrell Marc
• Fernandez Antonio
• Benson Sam
• Barth Nicole D
• De Moliner Fabio

Classifications

• G01N2021/6439

  with indicators, stains, dyes, tags, labels, marks · CPC title

• G01N21/6428

  Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53) · CPC title

• C07D293/12

  Selenazoles; Hydrogenated selenazoles · CPC title

• C07D285/14

  condensed with carbocyclic rings or ring systems · CPC title

• C07D249/18

  Benzotriazoles · CPC title