Phenylethynylnaphthalene dyes and methods for their use

Patent metadata

Field	Value
Publication number	US-11084932-B2
Application number	US-201615553546-A
Country	US
Kind code	B2
Filing date	Feb 26, 2016
Priority date	Feb 26, 2015
Publication date	Aug 10, 2021
Grant date	Aug 10, 2021

Abstract

Compounds useful as fluorescent or colored dyes that enable visual detection of biomolecules and other analytes are disclosed. The compounds comprise a phenylethynylnapthalene moiety represented by the following structure (I):including salts thereof, wherein R1a, R1b, R1c, R1d, R1e, R1f, R2a, R2b, R2c, R2d, R2e, R2f, R2g, R2h, R2i, R2j, x and y are as defined herein. Methods associated with preparation and use of such compounds for visually detecting a biomolecule are also provided.

First claim

What is claimed is:

1. A compound having the following structure

or a salt thereof, wherein:
R 1a is -L 1 -(R 3 ) z -L 2 -M or -L 1 -(R 3 ) z -L 2 —S—S—L 2 -(R 3 ) z -L 1 —I, where I is, independently, a further compound of structure (I);
R 1b , R 1c , R 1d , R 1e and R 1f are each independently H, halo, nitro, C 1 -C 6 alkyl, —SO 3 − , —SO 3 alkyl, C 1 -C 6 alkoxy, aryl, aryloxy, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkylcarbonyloxy, arylcarbonyl, arylcarbonyloxy, amino, alkylamino, arylamino, aralkylamino, -L 1 -(R 3 ) z -L 2 -M or -L 1 -(R 3 ) z -L 2 —S—S—L 2 -(R 3 ) z -L 1 —I, where I is, independently, a further compound of structure (I); or one of R 1a , R 1b , R 1c , R 1d , R 1e or R 1f joins with another one of R 1a , R 1b , R 1c , R 1d , R 1e or R 1f to form a carbocyclic or heterocyclic ring and the remaining R 1a , R 1b , R 1c , R 1d , R 1e and R 1f are each independently H, halo, nitro, C 1 -C 6 alkyl, —OSO 2 − , —OSO 2 alkyl, C 1 -C 6 alkoxy, aryl, aryloxy, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkylcarbonyloxy, arylcarbonyl, arylcarbonyloxy, amino, alkylamino, arylamino, or aralkylamino;
R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 2h , R 2i and R 2j are each independently H, halo, C 1 -C 6 alkoxy, aryloxy, amino, alkylamino, arylamino, aralkylamino, or heterocyclyl; or one or more of R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 2h , R 2i or R 2j join with another one or more of R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 2h , R 2i or R 2j on the same ring to form a mono or fused bicyclic carbocyclic or heterocyclic ring and the remaining R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 2h , R 2i and R 2j are each independently H, halo, C 1 -C 6 alkoxy, aryloxy, amino, alkylamino, arylamino, aralkylamino, or heterocyclyl;
R 3 is, at each occurrence, independently a mono or bivalent functional group selected from the group consisting of polyalkylether, polyalkylenether, hydroxylalkoxy, hydroxylalkyl, hydroxylalkylene, aminoalkylene, aminoalkoxy, hydroxylpolyalkylether, hydroxylpolyalkylenether, aminopolyalkylether, aminopolyalkylenether, phosphate, thiophosphate, phospho, thiophospho, phosphoalkyl, phosphoalkylene, phosphoalkylether, thiophosphoalkyl, thiophosphoalkylene, thiophosphoalkylether, phosphoramidite and activated phosphorous;
M is sulfhydryl, disulfide, an activated ester, isothiocyanate, azide, alkyne, alkene, diene, dienophile, acid halide, sulfonyl halide, phosphine, α-haloamide, biotin, amino or a maleimide; or M is an analyte molecule or solid support;
L 1 and L 2 are, at each occurrence, independently an optional linker;
x and y are each independently an integer from 0 to 4, and the sum of x and y is 2 or greater; and
z is an integer from 1 to 10.

2. The compound of claim 1 , wherein the sum of x and y is 2.

3. The compound of claim 1 , wherein x is 0 and y is 2.

4. The compound of claim 1 , wherein the compound has the following structure (Ia):

5. The compound of claim 4 , wherein the compound has the following structure (Ia′):

6. The compound of claim 1 , wherein R 1a is -L 1 -(R 3 ) z -L 2 -M.

7. The compound of claim 1 , wherein at least one of R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 2h , R 2i or R 2j is amino, alkylamino, arylamino, aralkylamino or heterocyclyl.

8. The compound of claim 1 , wherein one or more of R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 2h , R 2i or R 2j join with another one or more of R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 2h , R 2i or R 2j on the same ring to form a mono or fused bicyclic carbocyclic or heterocyclic ring and the remaining R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 2h , R 2i and R 2j are each independently H, halo, C 1 -C 6 alkoxy, aryloxy, amino, alkylamino, arylamino, aralkylamino, or heterocyclyl.

9. The compound of claim 8 , wherein the compound has one of the following structures:

10. The compound claim 1 , wherein at least one of R 2a , R 2b , R 2c , R 2d , R 2e , R 2f , R 2g , R 2i or R 2j is halo, alkoxy or aryloxy.

11. The compound of claim 1 , wherein each of R 2a , R 2b , R 2d , R 2e , R 2f , R 2g , R 2i and R 2j is H.

12. The compound of claim 1 , wherein R 1b , R 1c , R 1d , R 1e and R 1f are each independently H, halo, nitro, C 1 -C 6 alkyl, —SO 3 − , —SO 3 alkyl, C 1 -C 6 alkoxy, aryl, aryloxy, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkylcarbonyloxy, arylcarbonyl, arylcarbonyloxy, amino, alkylamino, arylamino, or aralkylamino.

13. The compound of claim 1 , wherein one of R 1b , R 1c , R 1d , R 1e or R 1f joins with another one of R 1b , R 1c , R 1d , R 1e or R 1f to form a carbocyclic or heterocyclic ring and the remaining R 1b , R 1c , R 1d , R 1e and R 1f are each independently H, halo, nitro, C 1 -C 6 alkyl, —OSO 2 − , —OSO 2 alkyl, C 1 -C 6 alkoxy, aryl, aryloxy, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkylcarbonyloxy, arylcarbonyl, arylcarbonyloxy, amino, alkylamino, arylamino, or aralkylamino.

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

15. The compound of claim 1 , wherein -(R 3 ) z -L 2 -M has one of the following structures:

16. The compound of claim 1 , wherein R 3 is phosphoramidite and M is sulfhydryl, disulfide, an activated ester, isothiocyanate, azide, alkyne, alkene, diene, dienophile, acid halide, sulfonyl halide, phosphine, α-haloamide, biotin, amino or a maleimide.

17. The compound of claim 1 , wherein the activated ester comprises N-succinimide ester, imidoester or polyflourophenyl ester.

18. The compound of claim 1 , wherein M is an analyte molecule or solid support.

19. A compound having one of the following structures:

or a salt thereof, where M is H, sulfhydryl, disulfide, N-succinimide ester, imidoester, polyflourophenyl ester, isothiocyanate, azide, alkyne, alkene, diene, dienophile, acid halide, sulfonyl hal

Assignees

• Sony Group Corp

Inventors

• Battrell C Frederick
• Matray Tracy
• Sherif Hesham
• Vanbrunt Michael

Classifications

• C09B23/141

  Bis styryl dyes containing two radicals C6H5-CH=CH- · CPC title

• C07F9/094

  with arylalkanols · CPC title

• C07F9/2429

  of arylalkanols · CPC title

• C09B69/00

  Dyes not provided for by a single group of this subclass · CPC title

• C07F9/572

  Five-membered rings · CPC title