Fluorescent dyes

Patent metadata

Field	Value
Publication number	US-9416153-B2
Application number	US-201113270456-A
Country	US
Kind code	B2
Filing date	Oct 11, 2011
Priority date	Oct 11, 2011
Publication date	Aug 16, 2016
Grant date	Aug 16, 2016

Abstract

Provided are various compounds comprising the formula

Also provided are fluorescent dyes comprising the above compound. Additionally, a fluorescence energy transfer system is provided that comprises the above-described fluorescent dye and a second dye, wherein the second dye is capable of energy transfer with the fluorescent dye. Further provided is a kit for labeling a target molecule, where the kit comprises the above-described fluorescent dye with additional reagents useful for labeling the target molecule. Additionally provided is a target molecule labeled with the above-described fluorescent dye. Methods of labeling a target molecule with the above-described fluorescent dye are also provided.

First claim

What is claimed is:

1. A compound having the formula

wherein
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are independently H, F, Cl, Br, I, CN, nitro, azido, hydroxyl, amino, hydrazino, (substituted) aryl, (substituted) aryloxy, alkenyl, alkynyl, alkyl, alkoxy, alkylamino, dialkylamino, arylamino, diarylamino, alkyl(aryl)amino, alkanoylamino, alkylthio, alkylcarbonyl, aryl carbonyl, alkylthiocarbonyl, arylthiocarbonyl, alkyloxycarbonyl, aroxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, alkyl(aryl)aminocarbonyl, arylcarboxamido, or Q, the alkyl or alkoxy portions of which are saturated or unsaturated, linear or branched, unsubstituted or further substituted by F, Cl, Br, I, CN, OH, alkenyl, alkynyl, alkylcarbonyl, amide, thioamide, or Q;
Q is selected from the group consisting of a carboxyl group (CO 2 − ), a carbonate ester (COER 11 ), a sulfonate ester (SO 2 ER 11 ), a sulfoxide (SOR 11 ), a sulfone (SO 2 CR 11 R 12 R 13 ), a sulfonamide (SO 2 NR 11 R 12 ), a phosphate, a phosphate monoester (PO 3 − ER 11 ), a phosphate diester (PO 2 ER 11 ER 12 ), a phosphonate, a phosphonate monoester (PO 2 − ER 11 ), a phosphonate diester (POER 11 ER 12 ), a thiophosphate, a thiophosphate monoester (PSO 2 − ER 11 ), a thiophosphate diester (PSOER 11 ER 12 ), a thiophosphonate, a thiophosphonate monoester (PSO − ER 11 ), a thiophosphonate diester (PSER 11 ER 12 ), a phosphonamide (PONR 11 R 12 NR 14 R 15 ), a phosphonamide thioanalogue (PSNR 11 R 12 NR 14 R 15 ), a phosphoramide (PONR 11 R 12 NR 13 NR 14 R 15 ), a phosphoramide thioanalogue (PSNR 11 R 12 NR 13 NR 14 R 15 S), a phosphoramidite (PO 2 R 14 NR 11 R 12 ), and a phosphoramidite thioanalogue (POSR 14 NR 11 R 12 ), where E can independently be O or S, and where the aryl portions of any of the above are optionally substituted by F, Cl, Br, I, CN, OH, alkenyl, alkynyl, alkylcarbonyl, amide, or thioamide;
R 1 in combination with R 2 , R 3 in combination with R 4 , R 5 in combination with R 6 , or R 9 in combination with R 10 can independently form a 5-10 member ring structure which is saturated or unsaturated, and which is optionally further substituted with an alkyl, an aryl, an alkenyl, an alkynyl, an alkoxy, an aryloxy, a hydroxyl, an F, Cl, Br, I, CN, a nitro, an alkylsulfonyl, an arylsulfonyl, an alkylsulfinyl, an arylsulfinyl, a (thio)carbonyl, a (thio)carboxylic acid, a (thio)carboxylic acid ester, a nitro, an amino, a (thio)amide, an azido, a hydrazino, or a (thio)phosphonate where each alkyl group or alkoxy group is independently saturated or unsaturated, linear or branched, or substituted or unsubstituted and each aryl group wherein is independently optionally substituted with F, Cl, Br, I, CN, OH, an alkyl, an alkenyl, an alkynyl, an alkoxy, an aryoxy, an alkylthio, an arylthio, a nitro, an azido, a hydrazino, a carboxyl, a thiocarboxyl, a carbonyl, a thiocarbonyl, a carboxylic acid ester, a thiocarboxylic acid ester, or an amino, amide, thioamide, or Q;
R 11 , R 12 , R 13 , R 14 and R 15 are independently a hydrogen, a halogen, an amino group, an alkyl group wherein said alkyl group is saturated or unsaturated, linear or branched, or substituted or unsubstituted, an alkoxy group wherein said alkoxy group is saturated or unsaturated, branched or linear, or substituted or unsubstituted, an aryl group wherein said aryl group is unsubstituted or substituted; wherein R 11 in combination with R 12 , R 14 in combination with R 15 , R 11 in combination with R 13 , R 11 in combination with R 14 , R 12 in combination with R 15 , or R 13 in combination with R 14 can independently form a 5-10 member ring;
X is O, OR 16 , NR 17 R 18 or N + R 17 R 18 ; Y is O, OR 16 , NR 19 R 20 or N + R 19 R 20 , wherein R 16 , R 17 , R 18 , R 19 and R 20 are independently H, alkyl, alkenyl, alkynyl, or aryl; or R 17 in combination with R 18 , or R 19 in combination with R 20 can independently form a 5-10 member ring structure which is optionally further substituted with alkyl, alkenyl, alkynyl, aryl, alkoxy, F, Cl, Br, I, carboxylic acid or carboxylic acid ester, where the alkyl group is saturated or unsaturated, linear or branched, and is optionally further substituted by F, Cl, Br, I, CN, OH, alkenyl, alkynyl, nitro, azido, hydrazino, alkoxy, aryoxy, alkylthio, arylthio, thiocarboxyl, carbonyl, thiocarbonyl, thiocarboxylic acid ester, amino, amide, thioamide, or Q, and the aryl group wherein is optionally substituted by F, Cl, Br, I, CN, OH, alkoxy, aryoxy, alkylthio, arylthio, nitro, azido, hydrazino, carboxyl, thiocarboxyl, carbonyl, thiocarbonyl, carboxylic acid ester, thiocarboxylic acid ester, amino, amide, thioamide, or Q;
R 17 in combination with R 6 , R 18 in combination with R 7 , R 19 in combination with R 8 , and R 20 in combination with R 9 , can independently form a 5- to 10-member ring structure that is saturated or unsaturated and optionally further substituted with an alkyl, an aryl, an alkenyl, an alkynyl, an alkoxy, an aryloxy, a hydroxyl, F, Cl, Br, I, CN, a nitro, a carbonyl, a thiocarbonyl, a thiocarboxylic acid, a thiocarboxylic acid ester, a nitro, an amino, a (thio)amide, an azido, a hydrazino, or Q, wherein the alkyl group herein is saturated or unsaturated, linear or branched, substituted or unsubstituted, an alkoxy group wherein the alkoxy group is saturated or unsaturated, branched or linear, substituted or unsubstituted; and wherein the aryl group is optionally substituted with F, Cl, Br, I, CN, OH, alkenyl, alkynyl, alkoxy, aryoxy, alkylthio, arylthio, nitro, azido, hydrazino, carboxyl, thiocarboxyl, carbonyl, thiocarbonyl, carboxylic acid ester, thiocarboxylic acid ester, amino, amide, thioamide, or Q;
-A-B—Z is

wherein n is 1-10, and
wherein Z is a reactive group selected from the group consisting of an isocyanate, an isothiocyanate, a monochlorotriazine, a dichlorotriazine, a 4,6-dichloro-1,3,5-triazines, a mono- or di-halogen substituted pyridine, a mono- or di-halogen substituted diazine, a maleimide, a haloacetamide, an aziridine, a sulfonyl halide, a carboxylic acid, an acid halide, a phosphonyl halide, a phosphoramidite (PO 2 R 14 NR 11 R 12 ), a phosphoramidite thioanalogue (POSR 14 NR 11 R 12 ), a hydroxysuccinimide ester, a hydroxysulfosuccinimide ester, an imido ester, an azido, a nitrophenol ester, an azide, a 3-(2-pyridyl dithio)-propionamide, a glyoxal, an aldehyde, a thiol, an amine, a hydrazine, a hydroxyl, a terminal alkene, a terminal alkyne, a platinum coordinate group and an alkylating agent; and

the carbon length for said alkenyl, alkynyl, and alkyl groups is from 1-16.

2. The compound of claim 1 , wherein n is 1-4.

3. The compound of claim 1 , wherein -A-B—Z is

4. The compound of claim 1 , wherein -A-B—Z is

5. The compound of claim 1 , having the structure:

6. The compound of claim 5 , wherein R 6 and R 9 are both H or CH 3 .

7. The compound of claim 5 , wherein X and Y are
(a) OH and O, respectively;
(b) NHCH 2 CH 3 and NCH 2 CH 3 , respectively; or
(c) N(CH 3 ) 2 and N + (CH 3 ) 2 , respectively.

8. A compound selected from the group consisting of:

Assignees

• Li Zaiguo
• Pande Praveen
• Enzo Life Sciences Inc

Inventors

• Li Zaiguo
• Pande Praveen

Classifications

• C09B11/24

  Phthaleins containing amino groups {; Phthalanes; Fluoranes; Phthalides; Rhodamine dyes; Phthaleins having heterocyclic aryl rings; Lactone or lactame forms of triarylmethane dyes} · CPC title

• C07H19/04 Primary

  Heterocyclic radicals containing only nitrogen atoms as ring hetero atom · CPC title

• C07H21/00 Primary

  Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids · CPC title

• C12Q1/707

  non-A, non-B Hepatitis, excluding hepatitis D · CPC title

• C07D311/88

  Nitrogen atoms · CPC title