Anthracenyl-tetralactam macrocycles and their use in detecting a target saccharide

Patent metadata

Field	Value
Publication number	US-9937272-B2
Application number	US-201715445710-A
Country	US
Kind code	B2
Filing date	Feb 28, 2017
Priority date	Apr 27, 2012
Publication date	Apr 10, 2018
Grant date	Apr 10, 2018

Abstract

A water-soluble compound of the formula (I):

wherein R 9 and R 10 are suitably hydrophilic substituents, which may be used to selectively bind to a target saccharide such as glucose and which exhibits a detectable spectroscopic response to such binding, thus enabling its use in the detection and correction of blood glucose concentrations in vivo.

First claim

The invention claimed is:

1. A water-soluble compound of the formula (I):

wherein R 1 to R 8 are each independently selected from hydrogen; optionally substituted alkyl groups; optionally substituted cycloalkyl groups; optionally substituted heterocyclyl groups; optionally substituted alkenyl groups; optionally substituted alkynyl groups; optionally substituted aryl groups; optionally substituted heteroaryl groups; alkoxyl groups; ketone and aldehyde groups; carboxylic acids and carboxylate ions; carboxylate esters; —SO 3 H; —SO 3 − ; —OSO 3 H; —OSO 3 − ; —PO 3 XY where X and Y are independently hydrogen, alkyl or a negative charge; —OPO 3 XY where X and Y are independently hydrogen, alkyl or a negative charge; amines; amides; halo groups; —CN; —NO 2 ; —OH; and imino and imido groups, provided that in any one or more of the pairs R 1 R 2 , R 3 R 4 , R 5 R 6 and R 7 R 8 , the two substituents may be joined together to form part of an optionally substituted cyclic group; and
R 9 and R 10 are each independently selected from hydrogen or hydrophilic substituents comprising two or more hydrophilic functional groups selected from carboxylic acids, carboxylate ions, carboxylate esters, hydroxyl, amines, amides, ethers, ketone and aldehyde groups, —NO2, sulphates, sulphonates, phosphates, phosphonates, and combinations thereof; and
wherein at least one of R 9 or R 10 is a hydrophilic substituent.

2. A compound according to claim 1 , wherein said two or more hydrophilic functional groups are selected from carboxylic acids, carboxylate ions, amides, ethers and combinations thereof.

3. A compound according to claim 1 or 2 , wherein R 1 to R 8 are selected from hydrogen, carboxylate esters, alkoxyl groups, optionally substituted cyclic imido groups, hydroxyl and sulphonates.

4. A compound according to claim 1 , wherein R 1 to R 8 are all hydrogen.

5. A compound according to claim 1 , wherein the at least one hydrophilic substituent is selected from groups of the formula —C(O)—R 14 , where R 14 is selected from:
a. groups —NR 15 C(R 16 CO 2 H) 3 in which R 15 is selected from hydrogen and C1 to C4 alkyl; and R 16 is a group (CH 2 ) n , where n is an integer from 1 to 6, optionally containing an ether group —O—;
b. groups —NR 15 C(R 17 ) 3 in which R 15 is as defined above; R 17 is a group —R 18 C(O)NR 15 —C(R 18 CO 2 H) 3 ; and each R 18 is independently selected from groups R 16 as defined above; and
c. groups —NR 15 C(R 25 ) 3 in which R 15 is as defined above; R 25 is a group —R 18 C(O)NR 15 —C(R 26 ) 3 ; R 26 is a group —R 18 C(O)NR 15 —C(R 18 CO 2 H) 3 ; and each R 18 is independently selected from groups R 16 as defined above.

6. A compound according to claim 1 , which has one of the formulae shown below:

7. A compound according to claim 1 , which has the formula:

or a salt or protected form thereof.

8. A compound according to claim 1 , which exhibits a spectroscopic response on complexing with a target saccharide, in particular glucose, which spectroscopic response is preferably detectable in the visible and/or near-infrared region of the electromagnetic spectrum.

9. A compound according to claim 1 , which is immobilised on or in a solid or semi-solid support.

10. A compound according to claim 9 , wherein the solid or semi-solid support is a polymeric matrix and/or a gel, such as a hydrogel.

11. A compound according to claim 10 , wherein the polymeric matrix and/or gel is a polymer selected from cross-linked polyethylene glycol and/or polyacrylamide.

12. A compound according to claim 10 or 11 , wherein the compounds are chemically linked to the polymeric matrix and/or gel.

13. A compound according to claim 10 or 11 , wherein the compounds are physically incorporated within the polymeric matrix and/or gel via non-covalent interactions.

Assignees

• Univ Bristol

Inventors

• Ke Chenfeng
• Davis Anthony P

Classifications

• A61B5/1455

  using optical sensors, e.g. spectral photometrical oximeters · CPC title

• G01N2800/042

  Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism · CPC title

• G01N33/66

  involving blood sugars, e.g. galactose · CPC title

• C07D257/10 Primary

  condensed with carbocyclic rings or ring systems · CPC title

• G01N33/52

  Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper {and including single- and multilayer analytical elements (immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72)} · CPC title