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

Patent metadata

Field	Value
Publication number	US-9610365-B2
Application number	US-201314397254-A
Country	US
Kind code	B2
Filing date	Apr 26, 2013
Priority date	Apr 27, 2012
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

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 method for detecting a target saccharide in an aqueous environment, the method comprising introducing, into the aqueous environment, a compound of formula (I) or a polymer incorporating the compound, and detecting a spectroscopic response of the compound or the polymer, to the aqueous environment, wherein the compound is as shown below:

wherein R 1 to R 8 are each independently selected from the group consisting of: hydrogen; an optionally substituted alkyl group; an optionally substituted cycloalkyl group; an optionally substituted heterocyclyl group; an optionally substituted alkenyl group; an optionally substituted alkynyl group; an optionally substituted aryl group; an optionally substituted heteroaryl group; an alkoxyl group; a ketone group, an aldehyde group; a carboxylic acid group, a carboxylate ion; a carboxylate ester; —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; an amine; an amide; a halo group; —CN; —NO 2 ; —OH; an imino, and an imido group, 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 hydrogen or a polar, hydrophilic substituent wherein the polar, hydrophiic substituent is —C(O)—R 14 , wherein R 14 is selected from the group consisting of:
a. —NR 15 C(R 16 CO 2 H) in which R 5 is selected from hydrogen or C1 to C4 alkyl; and R 16 is (CH 2 ) n , wherein n is an integer from 1 to 6, optionally containing an ether group —O—;
b. —NR 15 C(R 7 ) 3 in which R 15 is as defined above; R 17 is —R 18 C(O)NR 15 —C(R 18 CO 2 H) 3 ; and each R 18 is independently R 16 as defined above; and
c. —NR 15 C(R 25 ) 3 in which R 15 is as defined above; R 25 is —R 18 C(O)NR 15 —C(R 26 ) 3 ; R 26 is —R 18 C(O)NR 15 —C(R 18 CO 2 H) 3 ; and each R 18 is independently R 16 as defined above.

2. The method of claim 1 , wherein the target saccharide is glucose.

3. The method of claim 1 , wherein the compound is water soluble.

4. The method of claim 1 , wherein at least one of R 9 and R 10 is a polar, hydrophilic substituent.

5. The method of claim 1 , wherein R 1 to R 8 are hydrogen.

6. The method of claim 1 , wherein the compound is:

or a salt or protected form thereof.

7. The method of claim 1 , wherein detecting the spectroscopic response comprises detecting a change in one or more of the electromagnetic absorption, reflectance, transmission, or emission spectrum of the compound or the polymer in the aqueous environment.

8. The method of claim 1 , wherein the compound exhibits the spectroscopic response upon complexing with the target saccharide and which spectroscopic response is detectable in one or both of the visible or the near-infrared region of the electromagnetic spectrum.

9. The method of claim 1 , wherein the method is a method of diagnosis involving the diagnosis of a condition which results in, or is associated with, an abnormal concentration of or a change in the concentration of the target saccharide in a human or animal patient.

10. The method of claim 9 , wherein the change in the concentration of the target saccharide is in the bloodstream of the patient.

11. The method of claim 1 , wherein the aqueous environment is blood.

12. The method of claim 1 , wherein the compound is immobilised on or in a solid or semi-solid support.

13. The method of claim 12 , wherein the solid or semi-solid support is a polymeric matrix.

14. The method of claim 1 , wherein the polymer comprises the compound of formula (I) chemically linked to the remainder of the polymer via one or more polymerisable functional groups.

15. The method of claim 14 , wherein the one or more polymerisable functional groups form part of one or more of R 1 to R 10 .

16. The method of claim 15 , wherein the one or more polymerisable functional groups form part of R 9 , R 10 , or both.

17. The method of claim 2 , further comprising detecting the presence or otherwise of the target saccharide in the aqueous environment.

18. The method of claim 1 , further comprising detecting information about the concentration of the target saccharide.

19. The method of claim 1 , wherein the compound or the polymer itself exhibits a detectable response which changes with the concentration of the target saccharide in the aqueous environment.

20. The method of claim 1 , wherein one or both of R 9 and R 10 are independently selected from the group consisting of a carboxylic acid, a carboxylate ion, a carboxylate ester, a hydroxyl, an amine, an amide, an ether, a ketone, an aldehyde, —NO 2 , a sulphate, a sulphonate, a phosphate, and a phosphonate.

21. The method of claim 1 , wherein R 1 to R 8 are independently selected from the group consisting of a hydrogen, a carboxylate ester, an alkoxyl group, an optionally substituted cyclic imido group, a hydroxyl, and a sulphonate.

Assignees

• Univ Bristol

Inventors

• Ke Chenfeng
• Davis Anthony P

Classifications

• G01N33/66

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

• A61B5/1455

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

• C07D257/10 Primary

  condensed with carbocyclic rings or ring systems · CPC title

• A61K49/0004 Primary

  Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions · CPC title