# US 12,006,438 B2 · Polymeric dyes with linker groups comprising deoxyribose

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- Number: US 12,006,438 B2
- Document ID: US12006438B2
- Status: Granted
- Kind: B2
- Application number: 17/255,353
- Filed: 2019-06-27
- Published: 2022-07-14
- Granted: 2024-06-11
- Earliest claimed: 2018-06-27
- Assignees: Sony Group Corporation
- Applicants: Sony Corporation; Sony Corporation of America
- Inventors: Sharat Singh; Tracy Matray; Michael Vanbrunt; John McCutcheon
- Web page: https://patentgrep.com/patent/US12006438B2

## CPC

- C09B 69/102: {containing a perylene dye}
- C07H 21/04: with deoxyribosyl as saccharide radical
- C09B 69/103: {containing a diaryl- or triarylmethane dye}
- C09B 69/109: {containing other specific dyes}
- G01N 33/533: with fluorescent label
- G01N 33/582: {with fluorescent label}
- C09B: ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES {, e.g. PIGMENTS}; MORDANTS; LAKES (fermentation or enzyme using processes to synthesise a desired chemical compound C12P)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I): (I) or a stereoisomer, tautomer or salt thereof, wherein R1, R2, R3, R4, R5, L1a, L1b, L2, L3, L4, L5, L6, L7, M1, M2, q, w, m and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

## Claims

### Claim 1

A compound having the following structure (Ia):
or a stereoisomer, salt or tautomer thereof, wherein:
M1 is, at each occurrence, independently a moiety comprising a chromophore;
L1a is, at each occurrence, independently a heteroarylene linker;
L1b L2 and L3 are, at each occurrence, independently optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene or heteroalkynylene linkers;
L4 is, at each occurrence, independently an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene or heteroalkynylene linker;
R1 and R2 are each independently H, OH, SH, alkyl, alkoxy, alkylether, heteroalkyl, —OP(═Ra)(Rb)Rc, Q, or L′;
R4 is, at each occurrence, independently OH, SH, O−, S−, ORd or SRd;
R5 is, at each occurrence, independently oxo, thioxo or absent;
Ra is O or S;
Rb is OH, SH, O−, S−, ORd or SRd;
Rc is OH, SH, O−, S−, ORd, OL′, SRd, alkyl, alkoxy, heteroalkyl, heteroalkoxy, alkylether, alkoxyalkylether, phosphate, thiophosphate, phosphoalkyl, thiophosphoalkyl, phosphoalkylether or thiophosphoalkylether;
Rd is a counter ion;
Q is, at each occurrence, independently a moiety comprising a sulfhydryl, disulfide, activated ester, isothiocyanate, azide, alkyne, alkene, diene, dienophile, acid halide, sulfonyl halide, phosphine, α-haloamide, biotin, amino or maleimide functional group;
L′, at each occurrence, independently comprises an alkylene or heteroalkylene linker covalently bonded to: Q, a targeting moiety selected from an antibody and a cell surface receptor antagonist, an amino acid or polymer thereof, an enzyme, a receptor, a receptor ligand, a glycoprotein, an aptamer and a prion, an analyte molecule selected from a nucleic acid or polymer thereof, a solid support selected from a polymeric bead and a non-polymeric bead, or a nucleoside;
m is, at each occurrence, an integer of one or greater; and
n is an integer of one or greater.

### Claim 2 (depends on 1)

The compound of claim 1, wherein L1a has one of the following structures:

### Claim 3 (depends on 1)

The compound of claim 1, wherein at least one occurrence of L3 is an alkylene linker, and at least one occurrence of L4 comprises alkylene oxide.

### Claim 4 (depends on 1)

The compound of claim 1, wherein the compound has the following structure (Ib) or (Ic):
wherein:
L1b is, at each occurrence, independently an alkylene or heteroalkylene linker.

### Claim 5 (depends on 1)

The compound of claim 1, wherein L4 is polyethylene oxide, and the compound has the following structure (Id) or (Ie):
wherein:
z is an integer from 1 to 100.

### Claim 6 (depends on 1)

The compound of claim 1, wherein L1b, at each occurrence, independently comprises an amide functional group or a triazolyl functional group.

### Claim 7 (depends on 1)

The compound of claim 1, wherein R4 is, at each occurrence, oxo, and R5 is, at each occurrence, independently OH, O− or ORd.

### Claim 8 (depends on 1)

The compound of claim 1, wherein R1 and R2 are each independently —OP(═Ra)(Rb)Rc.

### Claim 9 (depends on 8)

The compound of claim 8, wherein Rc is OL′, wherein L′ comprises a heteroalkylene linker to: Q, a targeting moiety, an analyte molecule, a solid support, a solid support residue or a nucleoside.

### Claim 10 (depends on 9)

The compound of claim 9, wherein L′ comprises an alkylene oxide or phosphodiester moiety, or combinations thereof.

### Claim 11 (depends on 10)

The compound of claim 10, wherein L′ has the following structure:
wherein:
m″ and n″ are independently an integer from 1 to 10;
Re is H, an electron pair or a counter ion; and
L″ is Re or a direct bond or comprises an alkylene linkage to: Q, a targeting moiety, an analyte molecule, a solid support or a nucleoside.

### Claim 12 (depends on 11)

The compound of claim 11, wherein the targeting moiety is an antibody or cell surface receptor antagonist.

### Claim 13 (depends on 1)

The compound of claim 1, wherein R1 or R2 has one of the following structures:

### Claim 14 (depends on 1)

The compound of claim 1, wherein Q is a moiety having one of the following structures:
wherein:
X is halo; and
EWG is an electron withdrawing group.

### Claim 15 (depends on 1)

The compound of claim 1, wherein n is an integer from 1 to 10 and m is an integer from 3 to 12.

### Claim 16 (depends on 1)

The compound of claim 1, wherein M1 is, at each occurrence, independently pyrene, perylene, perylene monoimide or 6-carboxyfluorescein (6-FAM).

### Claim 17 (depends on 1)

The compound of claim 1, wherein M1, at each occurrence, independently has one of the following structures:

### Claim 18

A compound having one of the following structures:
wherein:
F″ is
wherein R is H or a direct bond.

### Claim 19 (depends on 1)

A method of staining a sample, comprising adding to said sample the compound of claim 1 in an amount sufficient to produce an optical response when said sample is illuminated at an appropriate wavelength.

### Claim 20 (depends on 1)

A method for visually detecting an analyte molecule, the method comprising:
(a) providing the compound of claim 1, wherein R1 or R2 is a linker comprising a covalent bond to the analyte molecule; and
(b) detecting the compound by its visible properties.

### Claim 21 (depends on 1)

A method for visually detecting an analyte molecule, the method comprising:
(a) admixing the compound of claim 1, wherein R1 or R2 is Q or a linker comprising a covalent bond to Q, with the analyte molecule;
(b) forming a conjugate of the compound and the analyte molecule; and
(c) detecting the conjugate by its visible properties.

### Claim 22 (depends on 1)

A method for visually detecting an analyte, the method comprising:
(a) providing the compound of claim 1, wherein R1 or R2 comprises a linker comprising a covalent bond to a targeting moiety having specificity for the analyte;
(b) admixing the compound and the analyte, thereby associating the targeting moiety and the analyte; and
(c) detecting the compound by its visible properties.

### Claim 23 (depends on 1)

A composition comprising the compound of claim 1 and one or more analyte molecules.

### Claim 24

A compound having the following structure (IIa):
or a stereoisomer, salt or tautomer thereof, wherein:
G1 is, at each occurrence, independently a moiety comprising an aldehyde, oxime, hydrazone, alkyne, amine, azide, acylazide, acylhalide, nitrile, nitrone, sulfhydryl, disulfide, sulfonyl halide, isothiocyanate, imidoester, activated ester, ketone, α,β-unsaturated carbonyl, alkene, maleimide, α-haloimide, epoxide, aziridine, tetrazine, tetrazole, phosphine, biotin or thiirane functional group;
L1a is, at each occurrence, independently a heteroarylene linker;
L1b′, L2 and L3 are, at each occurrence, independently optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene or heteroalkynylene linkers;
L4 is, at each occurrence, independently an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene or heteroalkynylene linker;
R1 and R2 are each independently H, OH, SH, alkyl, alkoxy, alkylether, heteroalkyl, —OP(═Ra)(Rb)Rc, Q, or L′;
R3 is, at each occurrence, independently H, alkyl or alkoxy;
R4 is, at each occurrence, independently OH, SH, O—, S—, ORd or SRd;
R5 is, at each occurrence, independently oxo, thioxo or absent;
Ra is O or S;
Rb is OH, SH, O—, S—,ORd or SRd;
Rc is OH, SH, O—, S—, ORd, OL′, SRd, alkyl, alkoxy, heteroalkyl, heteroalkoxy, alkylether, alkoxyalkylether, phosphate, thiophosphate, phosphoalkyl, thiophosphoalkyl, phosphoalkylether or thiophosphoalkylether;
Rd is a counter ion;
Q is, at each occurrence, independently a moiety comprising a sulfhydryl, disulfide, activated ester, isothiocyanate, azide, alkyne, alkene, diene, dienophile, acid halide, sulfonyl halide, phosphine, α-haloamide, biotin, amino or maleimide functional group;
L′, at each occurrence, independently comprises an alkylene or heteroalkylene linker covalently bonded to: Q, a targeting moiety selected from an antibody and a cell surface receptor antagonist, an amino acid or polymer thereof, an enzyme, a receptor, a receptor ligand, a glycoprotein, an aptamer and a prion, an analyte molecule selected from a nucleic acid or polymer thereof, a solid support selected from a polymeric bead and a non-polymeric bead, or a nucleoside;
m is, at each occurrence, an integer of one or greater; and
n is an integer of one or greater.

### Claim 25

A compound of structure (III) having one of the following structures:
wherein DMT is dimethoxytrityl.