Fluorogenic hydrazine-substituted compounds

Patent metadata

Field	Value
Publication number	US-2016356782-A1
Application number	US-201615176872-A
Country	US
Kind code	A1
Filing date	Jun 8, 2016
Priority date	Jan 24, 2008
Publication date	Dec 8, 2016
Grant date	—

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.

First claim

1 - 41 . (canceled)

42 . A compound of Formula V:

or a stereoisomer, tautomer, hydrate, solvate, or salt thereof;
wherein,
X is H or an analyte;
Z 1 a fluorophore and Z 2 is R 8 ; or
Z 1 is R 8 and Z 2 is a fluorophore;
R 5 , R 6 , R 8 and R 9 are each independently selected from the group consisting of H, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, halo, hydroxy, nitro, SO 3 − , sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, substituted alkylthio, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl; and
R 14 is selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, cycloalkyl, and substituted cycloalkyl; or
X and R 14 are taken together to form a fused heterocyclyl group, substituted fused heterocycyl group, fused heteroaryl group, or substituted fused heteroaryl group.

43 - 52 . (canceled)

53 . The compound of claim 42 , wherein Z 1 or Z 2 is:

R 18 , R 19 , R 20 , R 21 , R 22 , R 23 are each independently selected from the group consisting of H, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, halo, hydroxy, nitro, —SO 3 H, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, substituted alkylthio, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl.

54 - 56 . (canceled)

57 . The compound of claim 42 , wherein Z 1 or Z 2 is:

R 24 is selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl; and
R 25 , R 26 , R 27 , R 28 and R 29 are each independently selected from the group consisting of H, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, halo, hydroxy, nitro, —SO 3 H, sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, substituted alkylthio, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl.

58 - 60 . (canceled)

61 . The compound of claim 42 , wherein R 5 , R 6 , R 8 and R 14 are all H.

62 . The compound of claim 42 , wherein R 9 is —SO 3 − .

63 . The compound of claim 42 , wherein R 9 is —CO 2 − .

64 . The compound of claim 42 , wherein X is H.

65 . The compound of claim 42 , wherein X is an analyte.

66 . The compound of claim 65 , wherein the analyte is bound through an imine.

67 . The compound of claim 65 , wherein the analyte is 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.

68 - 71 . (canceled)

72 . A composition comprising:
(a) an analyte; and (b) a compound of Formula I:

or a stereoisomer, tautomer, hydrate, solvate, or salt thereof;
wherein,
X is H;
R 1 and R 1a are independently selected from the group consisting of H, alkyl and substituted alkyl;
R 2 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are each independently selected from the group consisting of H, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, halo, hydroxy, nitro, SO 3 − , sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, substituted alkylthio, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl; and
R 3 is selected from the group consisting of alkoxy, substituted alkoxy, amino, substituted amino, hydrazinyl, alkyl, substituted alkyl, acyl, acylamino, acyloxy, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, halo, hydroxy, nitro, SO 3 − , sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, substituted alkylthio, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl; or
R 2 and R 3 , R 3 and R 4 , or R 2 , R 3 and R 4 are taken together to form a fused heterocyclyl group, a fused substituted heterocyclyl group, a fused aryl group, a fused substituted aryl group, a fused heteroaryl group or a fused substituted heteroaryl group.

73 - 91 . (canceled)

92 . A composition comprising:
(a) an analyte; and (b) a compound according to claim 42

93 - 94 . (canceled)

95 . 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:

or a stereoisomer, tautomer, hydrate, solvate, or salt thereof;
wherein,
X is H or an analyte;
Z is a fluorophore;
R 5 , R 6 , R 8 and R 9 are each independently selected from the group consisting of H, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, halo, hydroxy, nitro, SO 3 − , sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, substituted alkylthio, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heteroc

Assignees

• Life Technologies Corp

Inventors

• Chen Aimei
• Gee Kyle
• Kang Hee Chol

Classifications

• G01N21/6428

  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 title

• C09K2211/1022

  bridged by heteroatoms, e.g. N, P, Si or B · CPC title

• C09K2211/1088

  containing oxygen as the only heteroatom · CPC title

• G01N2021/6439

  with indicators, stains, dyes, tags, labels, marks · CPC title

• C09K2211/1007

  Non-condensed systems · CPC title