Ultra bright dimeric or polymeric dyes with rigid spacing groups

Patent metadata

Field	Value
Publication number	US-11434377-B2
Application number	US-201716090560-A
Country	US
Kind code	B2
Filing date	Mar 31, 2017
Priority date	Apr 1, 2016
Publication date	Sep 6, 2022
Grant date	Sep 6, 2022

Abstract

Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I) or a stereoisomer, tautomer or salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , L 1 , L 2 , L 3 , L 4 , L 5 , A, M, m and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

First claim

What is claimed is:

1. A compound having the following structure (I):

or a stereoisomer, salt or tautomer thereof, wherein:
A has, at each occurrence, independently one of the following structures:

wherein a 1 , a 2 and a 3 are, at each occurrence, independently a 5, 6 or 7-membered carbocyclic or heterocyclic ring and L 6 is a direct bond or a linker, wherein the wavy lines indicate linkages to -O-L 5 - and -L 4 -O- and wherein in the compound of structure (I), -O-L 5 - is covalently linked to a ring atom of the a 1 and -L 4 -O- is covalently linked to a ring atom of the a 3 ;
M is, at each occurrence, independently a fluorescent or colored moiety comprising two or more carbon-carbon double bonds and at least one degree of conjugation;

L 1 is at each occurrence, independently either: i) an optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene or heteroatomic linker; or ii) a linker comprising a functional group capable of formation by reaction of two complementary reactive groups;
L 2 , L 3 , L 4 and L 5 are, at each occurrence, independently an optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene or heteroatomic linker;
R 1 is, at each occurrence, independently H, alkyl or alkoxy;
R 2 and R 3 are each independently H, OH, SH, alkyl, alkoxy, alkylether, —OP(═R a )(R b )R c , Q, a linker comprising a covalent bond to Q, a linker comprising a covalent bond to an analyte molecule, a linker comprising a covalent bond to a solid support or a linker comprising a covalent bond to a further compound of structure (I), wherein: R a is O or S; R b is OH, SH, O − , S − , OR d or SR d ; R c is OH, SH, O − , S − , OR d , SR d , alkyl, alkoxy, alkylether, alkoxyalkylether, phosphate, thiophosphate, phosphoalkyl, thiophosphoalkyl, phosphoalkylether or thiophosphoalkylether; and R d is a counter ion;
Q is, at each occurrence, independently a moiety comprising a reactive group capable of forming a covalent bond with an analyte molecule, a solid support or a complementary reactive group Q′;
m is, at each occurrence, independently an integer of zero or greater, provided that at least one occurrence of m is an integer of one or greater; and
n is an integer of one or greater.

2. The compound of claim 1 , wherein A, at each occurrence, independently has one of the following structures:

3. The compound of claim 1 , wherein for at least one occurrence of L 1 , L 1 -M has the following structure:

wherein L 1a and L 1b are each independently optional linkers.

4. The compound of claim 1 , wherein for at least one occurrence of L 1 , L 1 -M has the following structure:

wherein L 1a and L 1b are each independently optional linkers.

5. The compound of claim 1 , wherein L 1 is at each occurrence, independently an optional alkylene or heteroalkylene linker.

6. The compound of claim 1 , wherein the compound has the following structure (IA):

wherein:
x 1 , x 2 , x 3 , x 4 , x 5 and x 6 are, at each occurrence, independently an integer from 0 to 6.

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

8. The compound of claim 1 , wherein R 2 and R 3 are each independently OH or —OP(═R a )(R b )R c .

9. The compound of claim 1 , wherein one of R 2 or R 3 is OH or —OP(═R a )(R b )R c , and the other of R 2 or R 3 is Q or a linker comprising a covalent bond to Q.

10. The compound of claim 1 , wherein one of R 2 or R 3 is OH or —OP(═R a )(R b )R c , and the other of R 2 or R 3 is a linker comprising a covalent bond to an analyte molecule or a linker comprising a covalent bond to a solid support, wherein the analyte molecule is a nucleic acid or polymer thereof, an amino acid or polymer thereof, an enzyme, receptor, receptor ligand, antibody, glycoprotein, aptamer or prion and the solid support is a polymeric bead or nonpolymeric bead.

11. The compound of claim 1 , wherein M is, at each occurrence, independently a dimethylaminostilbene, quinacridone, fluorophenyl-dimethyl-BODIPY, his-fluorophenyl-BODIPY, acridine, terrylene, sexiphenyl, porphyrin, benzopyrene, (fluorophenyl-dimethyl-difluorobora-diaza-indacene)phenyl, (bis-fluorophenyl-difluorobora-diaza-indacene)phenyl, quaterphenyl, bi-benzothiazole, ter-benzothiazole, bi-naphthyl, bi-anthracyl, squaraine, squarylium, 9, 10-ethynylanthracene or ter-naphthyl moiety.

12. The compound of claim 1 , wherein M is, at each occurrence, independently p-terphenyl, perylene, azobenzene, phenazine, phenanthroline, acridine, thioxanthrene, chrysene, rubrene, coronene, cyanine, perylene imide, or perylene amide or derivative thereof.

13. The compound of claim 1 , wherein M is, at each occurrence, independently a coumarin dye, resorufin dye, dipyrrometheneboron difluoride dye, ruthenium bipyridyl dye, energy transfer dye, thiazole orange dye, polymethine or N-aryl-1,8-naphthalimide dye.

14. The compound of claim 1 , wherein M is, at each occurrence, independently pyrene, perylene, perylene monoimide or 6-FAM or derivative thereof.

15. The compound of claim 1 , wherein M, at each occurrence, independently has one of the following structures:

16. The compound of claim 1 , wherein the compound has one of the following structures:

wherein:
m is from 1 to 10;
y 1 and y 2 are each independently from 1 to 6;
F, E, and Y have the following structures:

17. A method for visually detecting an analyte molecule, the method comprising:
(a) admixing the compound of claim 1 , wherein R 2 or R 3 is Q or a linker comprising a covalent bond to Q, with the analyte molecule, wherein Q is the reactive group capable of forming a covalent bond with the analyte;
(b) forming a conjugate of the compound and the analyte molecule; and
(c) detecting the conjugate by its visible properties.

Assignees

• Sony Corp

Inventors

• Matray Tracy
• Singh Sharat
• Vanbrunt Michael

Classifications

• G01N1/30

  Staining; Impregnating {; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis} · CPC title

• C09B69/109 Primary

  containing other specific dyes · CPC title

• C09B69/102 Primary

  containing a perylene dye · CPC title

• C07F9/65583

  each of the hetero rings containing nitrogen as ring hetero atom · CPC title

• G01N2015/1006

  for cytology · CPC title