Redoxindicators

• US 10,060,907 B2
• Filed: 08/21/2015
• Issued: 08/28/2018
• Est. Priority Date: 08/22/2014
• Status: Active Grant

• Current Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Gebauer, Peter, Heindl, Dieter, Horn, Carina, Fomin, Maksim
• Primary Examiner(s): Leeser, Erich A
• Application Number:
  US15/438,859
• Publication Number:
  US 20170191990A1
• Time in Patent Office: 1,103 Days
• CPC Class Codes: C07D 241/40 Benzopyrazines
• CPC Class Codes: C07D 241/42 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/52 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

Abstract

The present invention relates to a chemical compound or a salt or solvate thereof being a phenazine-, phenanthridine-, phenanthroline-, quinoline-, quinoxaline-, acridine-isoquinoline-, pyrazine- or pyridine-derivative comprising a conjugated π-system and a π-acceptor group, and to uses thereof. The present invention further relates to a chemistry matrix and to a test element comprising the chemical compound of the present invention. The present invention also relates to a method of determining the amount of an analyte in a test sample, comprising contacting said test sample with a chemical compound, with a chemistry matrix, or with a test element of the invention and estimating the amount of redox equivalents liberated or consumed by the chemical compound, by the chemical compound comprised in said chemistry matrix, or by the chemical compound comprised in said test element, in the presence of said test sample, thereby determining the amount of an analyte in said test sample. Moreover, the present invention relates to a system comprising a test element according to the present invention and a device comprising a sensor for measuring the amount of redox equivalents liberated or consumed.

Claims

1. A tricyclic chemical compound or a salt thereof, said tricyclic chemical compound comprising a tricyclic heterocyclic group covalently bound to a π

-acceptor group, having the general structure of formula (I)

2. The tricyclic chemical compound or a salt thereof of claim 1, wherein

(i) X is —

N— and

wherein the π

-system is covalently bonded to C1, C2, C3, or C4 of the heteroaromatic system as indicated in formula (I), or

(ii) X is —

CH— and

wherein the π

-system is covalently bonded to C2 or C4 of the heteroaromatic system as indicated in formula (I).

3. The tricyclic chemical compound or a salt thereof of claim 1, wherein

(i) X is —

N— and

wherein the π

-system is covalently bonded to C1 of the heteroaromatic system as indicated in formula (I), or

(ii) X is —

CH— and

wherein the π

-system is covalently bonded to C2 of the heteroaromatic system as indicated in formula (I).

4. The tricyclic chemical compound or a salt thereof of claim 1, wherein the it-acceptor group is selected from the list consisting of

(i) a side chain comprising the structure of formula (II)

5. The tricyclic chemical compound or a salt thereof of claim 1, wherein said chemical compound or a salt thereof is a compound undergoing a bathochromic shift upon reduction.

6. The tricyclic chemical compound or a salt thereof of claim 1, wherein in said chemical compound or salt thereof the π

-acceptor group is not reduced by reduced coenzymes NADH, FADH, or PQQH.

16. The tricyclic chemical compound or a salt thereof of claim 1, wherein said tricyclic chemical compound is 2-[(E)-2-(5-methyl-phenazin-1-yl)vinyl]-1,3,3-trimethyl-3H-indole (XX);

2-[(E)-2-(5-methyl-9-ethoxyphenazin-1-yl)vinyl]-1,3,3-trimethyl-3H-indole (XXI);

or 2-[(E)-2-(5-methyl-9-ethoxyphenazin-2-yl)vinyl]-1,3,3-trimethyl-3H-indole (LII).

17. The tricyclic chemical compound or a salt thereof of claim 1 in which R¹, R², R³, R⁴ are independently selected from hydrogen;

lower alkyl;

phenyl;

halide;

nitro;

sulfonate;

—

CN;

—

COOH;

—

OR⁹;

—

SR⁹;

—

SSR⁹;

—

C(O)OR⁹;

—

C(O)NHR⁹;

NHC(O)R⁹; and

—

C(O)NH₂.

18. The tricyclic chemical compound or a salt thereof of claim 1 in which R⁹ is selected from lower alkyl or phenyl.

19. The tricyclic chemical compound or a salt thereof of claim 1 in which each of R5, R6 and R8 is an π

-acceptor group.

20. The tricyclic chemical compound or a salt thereof of claim 1 in which R⁵ and R⁶ are independently selected from the group consisting of methyl, ethyl and phenyl.

21. The tricyclic chemical compound or a salt thereof of claim 1 in which n is selected from the group consisting of 0, 1 and 2.

22. The tricyclic chemical compound or a salt thereof of claim 4 in which R¹⁰ is methyl.

7. A chemistry matrix comprising a redox cofactor and a chemical compound or a salt thereof, said chemical compound comprising a heterocyclic group (Het) covalently bound to a π

-acceptor group (Acc), having the general structure of formula (VI)

8. The chemistry matrix of claim 7, wherein said chemical compound comprises a structure of any one of (XVII) to (XXVII), (XXX) to (XXXII), and (LII):

9. The chemistry matrix of claim 7, wherein said chemical compound is 1-Methyl-6-((E)-3-oxo-3-phenyl-propenyl)-quinoline (XXII) or 1-methyl-3-[(E)-2-(1,3,3-trimethyl-3H-indolium-2-yl)ethenyl]quinoline (XXV).

10. The chemistry matrix of claim 7, further comprising an oxidoreductase enzyme.

11. The chemistry matrix of claim 7, wherein said redox cofactor is nicotine adenine dinucleotide phosphate (NADP), pyrroloquinoline quinone (PQQ), flavine adenine dinucleotide (FAD), nicotine adenine dinucleotide (NAD) or carbaNAD, or a reduced form of any of the aforesaid redox cofactors.

12. The chemistry matrix of claim 7, wherein said chemical compound is a compound undergoing a bathochromic shift upon reduction.

13. The chemistry matrix of claim 7, wherein in said chemical compound the π

-acceptor group is not reduced by reduced coenzymes NADH, FADH, or PQQH.

14. A test element comprising the chemistry matrix of claim 7.

15. A system for determining the amount of an analyte in a sample, comprising

a) a test element according to claim 14 and

b) a device comprising a sensor for measuring the amount of redox equivalents liberated or consumed in said test element.

23. The chemistry matrix of claim 7 in which R¹¹ is selected from the group consisting of methyl, ethyl and phenyl.

24. The chemistry matrix of claim 7 in which l is selected from the group consisting of 0, 1 and 2.

25. The chemistry matrix of claim 8 which consists of a structure of any one of (XVII) to (XXVII), (XXX) to (XXXII) and (LII).