Senescence tracers

Patent metadata

Field	Value
Publication number	US-9829481-B2
Application number	US-201514632475-A
Country	US
Kind code	B2
Filing date	Feb 26, 2015
Priority date	Aug 28, 2012
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

Abstract

The instant invention relates to novel compounds useful for visualizing cell senescence, their preparation and use. In particular, this invention relates to novel fucose and amino-quinoline derivatives useful as senescence traces and their preparation.

First claim

What is claimed is:

1. Compound of formula
A-L-M  (I)

in which,
A represents

wherein,
* represents the binding site to the residue represented by L,

L represents *Y-(CH 2 ) n - # or

wherein,
Y is selected from the group consisting of O, N, S, SO and SO 2 ,
n is an integer from 2 to 6,
* represents the binding site to the residue represented by A, and
# represents the binding site to the residue represented by M, and

M represents a fluorophore, a residue comprising at least one atom selected from the group consisting of 76 Br, 75 Br, 18 F, 13 C and 11 C or a combination thereof,

and the salts thereof, the solvates thereof and the solvates of the salts thereof.

2. Compound according to claim 1 , wherein n is 2, 3 or 4.

3. Compound according to claim 1 , wherein M represents a fluorophore.

4. Compound according to claim 3 , wherein the fluorophore is selected from the group consisting of the xanthene derivatives, fluorescein, rhodamine, Oregon green, eosin, and Texas red, the cyanine derivatives, cyanine, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, and merocyanine, the naphthalene derivatives, a dansyl or derivatives thereof, the coumarin derivatives, the oxadiazole derivatives, pyridyloxazole, nitrobenzoxadiazole and benzoxadiazole, the pyrene derivatives, the oxazine derivatives, Nile red, Nile blue and cresyl violet, the acridine derivatives, proflavin, acridine orange and acridine yellow, the arylmethine derivatives, auramine, crystal violet and malachite green, and the tetrapyrrole derivatives, porphin, phthalocyanine and bilirubin.

5. Compound according to claim 1 , wherein M is selected from 76 Br, 75 Br, 18 F,

wherein,
X is selected from the group consisting of Br, 76 Br, 75 Br, Cl, F and 18 F,
R 1 represents hydrogen or (C 1 -C 6 )-alkyl,
whereby alkyl is substituted with one to three substituents selected independently from the group consisting of hydroxy, amino, cyano, nitro, halogen, carbonyl, (C 1 -C 4 )-alkoxy, mono (C 1 -C 4 )-alkylamino and di-(C 1 -C 4 )-alkylamino,
whereby R 1 represents an optionally substituted (C 1 -C 6 )-alkyl comprising at least one 76 Br, 75 Br, 18 F or 11 C if X is not 76 Br, 75 Br or 18 F,

R 2 and R 3 independently from one another represent hydrogen or (C 1 -C 6 )-alkyl,
whereby alkyl is substituted with one to three substituents selected independently form the group consisting of, hydroxy, amino, cyano, nitro, halogen, carbonyl, (C 1 -C 4 )-alkoxy, mono (C 1 -C 4 )-alkylamino and di-(C 1 -C 4 )-alkylamino,
whereby at least one of R 2 and R 3 represents a (C 1 -C 6 )-alkyl comprising at least one 11 C or being substituted with a residue comprising at least one 76 Br, 75 Br, 18 F or 11 C, and

* represents the binding site to the residue represented by L.

6. Medicament comprising a compound according to claim 1 in combination with at least one inert, non-toxic, pharmaceutically suitable excipient.

Assignees

• Univ Tuebingen Medizinische Fakultaet

Inventors

• Cotton Jonathan
• Pichler Bernd
• Fuchs Kerstin
• Teske Anna
• Krueger Marcel
• Kesenheimer Christian
• Schulze-Osthoff Klaus
• Hildebrand Dominic

Classifications

• G01N2800/7042

  Aging, e.g. cellular aging · CPC title

• G01N33/582 Primary

  with fluorescent label · CPC title

• C07H15/26

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title

• G01N33/5005 Primary

  involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025) · CPC title

• C07D215/46

  with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms · CPC title