Water-Soluble Tetrazolium Salts

• US 20080125471A1
• Filed: 01/13/2006
• Published: 05/29/2008
• Est. Priority Date: 01/14/2005
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Marfurt, Karen L., Albarella, James P, Landi, John J., Felman, Steven W.
• Granted Patent: US 7,767,822 B2
• Time in Patent Office: Days
• US Class Current: 514/370
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

Thiazolyl tetrazolium salts with increased solubility in aqueous solutions have alkylammonium alkoxy substituents, preferably trimethyl ammonium propoxy groups substituents, on phenyl rings attached to the tetrazolium ring. Thiazolyl tetrazolium salts with increased solubility in aqueous solutions have alkyl ammonium alkoxy substituents, preferably trimethyl ammonium propoxy groups substituents, on phenyl rings attached to the tetrazolium ring, e.g. the compounds of the general formula shown below. Formula (A-)_a.

Claims

1. A compound having the formula

2. The compound of claim 1 having the formula

3. The compound of claim 2, wherein

X is propyl

b is zero

R₁ is methyl

R₂ and R₃ form a methylene dioxy group

R₄ is CHF₂

R₅ is Cl.

4. The compound of claim 2, wherein

X is propyl

b is 1

R₁ is methyl

R₂ and R₃ form a methylene dioxy group

R₄ is CHF₂

R₅ is Cl.

5. The compound of claim 2, wherein

X is propyl

b is zero

R₁ is methyl

R₂ is trimethylammonium propyl

R₃ is methoxy

R₄ is CHF₂

R₅ is Cl.

6. The compound of claim 1 having the formula

7. The compound of claim 6, wherein

X is propyl

b is zero

R₁ is methyl

R₂ is trimethylammonium propyl

R₃ is methoxy.

R₄, R₅, and R₆ are hydrogen.

8. The compound of claim 6, wherein

X is propyl

R₁ is methyl

b is zero

R₂ is trimethylammonium propyl

R₃ is methyl

R₄ and R₅ form an aromatic ring

R₆ is methoxy.

9. The compound of claim 6, wherein

X is propyl

b is zero

R₁ is methyl

R₂ is trimethylammonium propyl

R₃ is methyl

R₄ and R₅ are hydrogen

R₆ is ethoxy.

10. The compound of claim 6, wherein

X is propyl

b is zero

R₁ is methyl

R₂ is trimethylammonium propyl

R₃ is methyl

R₄ and R₅ are hydrogen

R₆ is bromine.

11. The compound of claim 1, wherein said at least one counter-ion is nitrite, phosphate, hydrogenphosphate, dihydrogen phosphate, hydrogen sulfate, sulfate, hydrogen carbonate, carbonate, methane sulfonate, fluoroborate, bromide, chloride, iodide, or combinations thereof.

12. A method of measuring an analyte contained in a biological fluid, the analyte adapted to produce a proportional color change upon a reaction, the method comprising the acts of:

providing a tetrazolium salt as an indicator, said tetrazolium salt having the formula of

13. The method of claim 12, wherein said analyte is glucose.

14. The method of claim 13, wherein said biological fluid is whole blood.

15. The method of claim 13, wherein said tetrazolium salt has the formula

16. The method of claim 15, wherein

X is propyl

b is zero

R₁ is methyl

R₂ and R₃ form a methylene dioxy group R₄ is CHF₂

R₅ is Cl.

17. The method of claim 15, wherein

X is propyl

b is 1

R₁ is methyl

R₂ and R₃ form a methylene dioxy group

R₄ is CHF₂

R₅ is Cl.

18. The method of claim 15, wherein

X is propyl

b is zero

R₁ is methyl

R₂ is trimethylammonium propyl

R₃ is methoxy

R₄ is CHF₂

R₅ is Cl.

19. The method of claim 12 having the formula wherein:

a=1-3

20. The method of claim 19, wherein

X is propyl

b is zero

R₁ is methyl

R₂ is trimethylammonium propyl

R₃ is methoxy

R₄, R₅, and R₆ are hydrogen.

21. The method of claim 19, wherein

X is propyl

R₁ is methyl

b is zero

R₂ is trimethylammonium propyl

R₃ is methyl

R₄ and R₅ form an aromatic ring

R₆ is methoxy.

22. The method of claim 19, wherein

X is propyl

b is zero

R₁ is methyl

R₂ is trimethylammonium propyl

R₃ is methyl

R₄ and R₅ are hydrogen

R₆ is ethoxy.

23. The method of claim 19, wherein

X is propyl

b is zero

R₁ is methyl

R₂ is trimethylammonium propyl

R₃ is methyl

R₄ and R₅ are hydrogen

R₆ is bromine.

24. The method of claim 12, wherein said at least one counter-ion is nitrite, phosphate, hydrogenphosphate, dihydrogen phosphate, hydrogen sulfate, sulfate, hydrogen carbonate, carbonate, methane sulfonate, fluoroborate, bromide, chloride, iodide, or combinations thereof.

25. A method of increasing the solubility of thiazoyl tetrazolium salts having the thiazoyl group attached at the third nitrogen atom of the tetrazolium ring, the method comprising adding at least one trialkyl ammonium alkoxy group as a substituent to the thiazoyl tetrazolium salt.

26. The method of claim 25, wherein said thiazoyl tetrazolium salt has phenyl substituents at the third nitrogen atom and at the carbon atom of the tetrazolium ring.

27. The method of claim 26, wherein said at least one trialkyl ammonium alkoxy group is a trimethyl ammonium propoxy group.

28. The method of claim 26, wherein said at least one trialkyl ammonium alkoxy group is a substituent of said phenyl groups.

29. The method of claim 26, wherein at least one trialkyl ammonium alkoxy group is a substituent of both of said phenyl substituents.

30. The method of claim 25, wherein said thiazoyl group is a benzo thiazoyl group.

31. The method of claim 25, wherein said thiazoyl tetrazolium salt has counterions of nitrite, phosphate, hydrogen phosphate, dihydrogen phosphate, hydrogen sulfate, sulfate, hydrogen carbonate, carbonate, methane sulfonate, fluoroborate, bromode, chloride, iodide, or combinations thereof.

32. The method of claim 31, wherein said counterions are bromo nitrite, dibromo nitrite, or tribromide.