Azo mediators and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9840729-B2
Application number	US-201414226884-A
Country	US
Kind code	B2
Filing date	Mar 27, 2014
Priority date	Sep 28, 2011
Publication date	Dec 12, 2017
Grant date	Dec 12, 2017

Abstract

Azo compounds are disclosed that do not form azoxy dimers and that do not have any reactive nitroso groups. Also disclosed are use of the azo compounds as mediators in optical and electrochemical diagnostic methods, as well as detection reagents, kits and test elements that include such azo compounds and that can be used in the diagnostic methods.

First claim

The invention claimed is:

1. A detection reagent for determining presence or concentration of glucose, the detection reagent comprising:
(a) a flavine-, nicotinamide- or pyrroloquinoline quinone-dependent oxidoreductase;
(b) a reducible flavine, nicotinamide or pyrroloquinoline quinone coenzyme;
(c) an azo compound of the general formula (I):

wherein R 1 denotes a residue selected from the group consisting of OH, OR 7 , SR 7 , NHR 7 and NR 7 R 8 ;
wherein R 2 , R 3 , R 4 and R 5 independently of one another denote a residue selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heterocycloalkyl, heteroaryl, CN, COO − , halogen, O(alkyl), O(aryl), NH(alkyl), N(alkyl) 2 , N(alkyl) 3 + , NH(aryl), N(aryl) 2 , NO 2 and SO 3 − , and wherein the alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heterocycloalkyl, heteroaryl, O(alkyl), O(aryl), NH(alkyl), N(alkyl) 2 , N(alkyl) 3 + , NH(aryl) or N(aryl) 2 can contain one or more substituents selected from the group consisting of CN, COO − , halogen, NH 2 , NH(alkyl), N(alkyl) 2 , N(alkyl) 3 + , NH(aryl), N(aryl) 2 , NH—C(═NH 2 )—NH 2 + , NO 2 , OH, O—(CH 2 CH 2 ) n —OH, O—(CH 2 CH 2 ) n —O(alkyl), O(alkyl), O(aralkyl), O(aryl), OPO 3 2− , PO 3 2− and SO 3 − ;
wherein R 6 denotes a residue selected from the group consisting of CN, C(═X)NH 2 , C(═X)NHR 9 , C(═X)NR 9 R 10 , C(═X)NHOH and C(═X)R 9 ;
wherein R 7 and R 8 independently of one another denote a residue selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heterocycloalkyl and heteroaryl, and wherein the alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heterocycloalkyl or heteroaryl can contain one or more substituents selected from the group consisting of CN, COO − , halogen, NH 2 , NH(alkyl), N(alkyl) 2 , N(alkyl) 3 + , NH(aryl), N(aryl) 2 , NH—C(═NH 2 )—NH 2 + , NO 2 , OH, O—(CH 2 CH 2 ) n —OH, O—(CH 2 CH 2 ) n —O(alkyl), O(alkyl), O(aralkyl), O(aryl), OPO 3 2− , PO 3 2− and SO 3 − ;
alternatively wherein R 7 and R 8 together with the N atom to which they are bound form a 5-membered to 7-membered heterocycle, and wherein the heterocycle can contain a further heteroatom selected from the group consisting of N, O and S and/or one or more substituents selected from the group consisting of CN, COO − , halogen, NH 2 , NH(alkyl), N(alkyl) 2 , N(alkyl) 3 + , NH(aryl), N(aryl) 2 , NH—C(═NH 2 )—NH 2 + , NO 2 , OH, O—(CH 2 CH 2 ) n —OH, O—(CH 2 CH 2 ) n —O(alkyl), O(alkyl), O(aralkyl), O(aryl), OPO 3 2− , PO 3 2− and SO 3 − ;
wherein R 9 and R 10 independently of one another denote a residue selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heterocycloalkyl and heteroaryl, and wherein the alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heterocycloalkyl or heteroaryl can contain one or more substituents selected from the group consisting of CN, COO − , halogen, NH 2 , NH(alkyl), N(alkyl) 2 , N(alkyl) 3 + , NH(aryl), N(aryl) 2 , NH—C(═NH 2 )—NH 2 + , NO 2 , OH, O—(CH 2 CH 2 ) n —OH, O—(CH 2 CH 2 ) n —O(alkyl), O(alkyl), O(aralkyl), O(aryl), OPO 3 2− , PO 3 2− and SO 3 − ;
alternatively wherein R 9 and R 10 together with the N atom to which they are bound form a 5-membered to 7-membered heterocycle, and wherein the heterocycle can contain a further heteroatom selected from the group consisting of N, O and S and/or one or more substituents selected from the group consisting of CN, COO − , halogen, NH 2 , NH(alkyl), N(alkyl) 2 , N(alkyl) 3 + , NH(aryl), N(aryl) 2 , NH—C(═NH 2 )—NH 2 + , NO 2 , OH, O—(CH 2 CH 2 ) n —OH, O—(CH 2 CH 2 ) n —O(alkyl), O(alkyl), O(aralkyl), O(aryl), OPO 3 2− , PO 3 2− and SO 3 − ;
wherein X denotes a heteroatom selected from the group consisting of O and S, and wherein n denotes an integer from 1 to 6; and
(d) optionally a reducible optical indicator.

2. The detection reagent of claim 1 , wherein the flavine-, nicotinamide- or pyrroloquinoline quinone-dependent oxidoreductase is a flavine-, nicotinamide- or pyrroloquinoline quinone-dependent dehydrogenase.

3. The detection reagent of claim 2 , wherein the flavine-, nicotinamide- or pyrroloquinoline quinone-dependent glucose dehydrogenase is a glucose-6-phosphate dehydrogenase.

4. The detection reagent of claim 1 , wherein the reducible flavine, nicotinamide or pyrroloquinoline quinone coenzyme is selected from the group consisting of carbaNAD + , carbaNADP + , FAD, FMN, NAD + , NADP + , PQQ and derivatives thereof.

5. The detection reagent of claim 1 , wherein the azo compound is 4-[bis-(2-hydroxyethyl)-amino]-benzenediazocarbamide.

6. A kit for determining presence or concentration of glucose, the kit comprising:
(a) the detection reagent of claim 1 ; and
(b) an optical test element or an electrochemical test element.

7. A test element for determining presence or concentration of glucose, the test element comprising the detection reagent of claim 1 .

8. The test element of claim 6 , wherein the test element is an optical sensor or an electrochemical sensor.

9. A method of determining presence or concentration of glucose, the method comprising the steps of:
(a) contacting a sample comprising glucose with the test element of claim 7 ; and
(b) determining a presence and/or a concentration of glucose in the sample.

Assignees

• Roche Diabetes Care Inc

Inventors

• Duvall Stacy H
• Gebauer Peter
• Heindl Dieter
• Horn Carina
• Kratzsch Peter
• Marquant Michael
• Meier Thomas

Classifications

• C12Q1/54 Primary

  involving glucose or galactose · CPC title

• C07D295/215

  Radicals derived from nitrogen analogues of carbonic acid · CPC title

• C07C281/20 Primary

  the two nitrogen atoms of the functional groups being doubly-bound to each other, e.g. azoformamide · CPC title

• G01N31/22

  using chemical indicators (G01N31/02 takes precedence) · CPC title

• C12Q1/26

  involving oxidoreductase · CPC title