Fluorogenic hydrazine-substituted compounds

• US 10,006,918 B2
• Filed: 06/08/2016
• Issued: 06/26/2018
• Est. Priority Date: 01/24/2008
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Chen, Aimei, Gee, Kyle, Kang, Hee Chol
• Primary Examiner(s): Otton, Alicia L
• Application Number:
  US15/176,872
• Publication Number:
  US 20160356782A1
• Time in Patent Office: 748 Days
• Field of Search: None
• CPC Class Codes: C07D 311/82 Xanthenes
• CPC Class Codes: C07D 471/06 Peri-condensed systems
• CPC Class Codes: C07F 5/022 without C-boron linkages
• CPC Class Codes: C07F 9/5442 Aromatic phosphonium compounds (P-C aromatic linkage)
• CPC Class Codes: C07F 9/65522 condensed with carbocyclic rings or carbocyclic ring systems
• CPC Class Codes: C09B 11/24 Phthaleins containing amino groups ; Phthalanes; Fluoranes; Phthalides; Rhodamine dyes; Phthaleins having heterocyclic aryl rings; Lactone or lactame forms of triarylmethane dyes
• CPC Class Codes: C09K 11/06 containing organic luminescent materials
• CPC Class Codes: C09K 2211/10 Non-macromolecular compounds
• CPC Class Codes: C09K 2211/1007 Non-condensed systems
• CPC Class Codes: C09K 2211/1014 bridged by heteroatoms, e.g. N, P, Si or B
• CPC Class Codes: C09K 2211/1022 bridged by heteroatoms, e.g. N, P, Si or B
• CPC Class Codes: C09K 2211/1033 with oxygen
• CPC Class Codes: C09K 2211/1055 with other heteroatoms
• CPC Class Codes: C09K 2211/1088 containing oxygen as the only heteroatom
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/6428 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 Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 33/50 Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q
• CPC Class Codes: G01N 33/52 Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72
• CPC Class Codes: G01N 33/64 involving ketones
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]

Abstract

The present disclosure is directed to fluorogenic schiff base-forming dyes capable of detecting analytes containing aldehyde and ketone groups. The dyes contain nucleophilic hydrazinyl appendages and are capable of binding and detecting analytes in situ.

Claims

1. A compound of Formula V:

2. The compound of claim 1, wherein Z¹ or Z² is:

3. The compound of claim 1, wherein Z¹ or Z² is:

4. The compound of claim 1, wherein R⁵, R⁶, R⁸ and R¹⁴ are all H.

5. The compound of claim 1, wherein R⁹ is SO₃.

6. The compound of claim 1, wherein R⁹ is —

CO₂.

7. The compound of claim 1, wherein X is H.

8. The compound of claim 1, wherein X is an analyte selected from the group consisting of an amino acid, a peptide, a protein, a carbohydrate, a polysaccharide, a nucleoside, a nucleotide, an oligonucleotide, a nucleic acid polymer, a drug, a lipid, and a synthetic polymer.

9. The compound of claim 8, wherein the analyte is bound through an imine.

10. A composition comprising:

(a) an analyte selected from the group consisting of malondialdehyde, 4-hydroxynonenal, an amino acid, a peptide, a protein, a carbohydrate, a polysaccharide, a nucleoside, a nucleotide, an oligonucleotide, a nucleic acid polymer, a hapten, a psoralen, a drug, a hormone, a lipid, a lipid assembly, a synthetic polymer, a biotin-binding protein, a polymeric microparticle, a biological cell and a virus; and

(b) a compound according to claim 1.

11. A method for determining the presence of an analyte of interest in a sample, wherein the method comprises:

contacting the sample with compound of Formula V;

12. The method of claim 11, wherein the analyte and the compound are connected by a covalent bond.

13. The method of claim 11, wherein the compound becomes fluorescent after formation of the complex.

14. The method of claim 12, wherein the analyte is bound to the compound through an imine.

15. The method of claim 11, wherein the analyte is malondialdehyde or 4-hydroxynonenal.

16. The method of claim 11, wherein the analyte comprises an aldehyde group.

17. A kit for detecting an analyte in a sample, wherein the kit comprises:

a compound of Formula V that binds an analyte;