Labelled boronic acid derivatives

• US 5,631,364 A
• Filed: 03/31/1994
• Issued: 05/20/1997
• Est. Priority Date: 03/31/1994
• Status: Expired due to Term

• Current Assignee: Axis-Shield ASA (Abbott Laboratories)
• Original Assignee: Axis Biochemicals ASA
• Inventors: Sundrehagen, Erling, Frantzen, Frank
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US08/220,525
• Time in Patent Office: 1,146 Days
• Field of Search: 540/128, 544/69, 546/13, 548/110, 548/405, 549/4, 549/213, 552/109, 562/7
• US Class Current: 540/128
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: G01N 33/532 Production of labelled immunochemicals
• CPC Class Codes: Y10S 436/815 Test for named compound or class of compounds
• CPC Class Codes: Y10S 436/825 Pretreatment for removal of interfering factors from sample
• CPC Class Codes: Y10T 436/25125 Digestion or removing interfering materials
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

The invention provides novel labelled boronic acid conjugates of formula ##STR1## (wherein V is a reporter moiety; W² is a bond or an organic linker moiety;

W¹ is a *SO₂ NR², *CON² or *CH₂ N⊕R² ₂ group bound at the *-marked atom to the phenyl ring;

R¹ is hydrogen or an electron withdrawing substituent group; and

each R² independently is hydrogen or an optionally hydroxylated and optionally C_1-6 -alkoxylated C_1-6 -alkyl group) and salts thereof, e.g. for use in assays for cis-diols such as glycated blood proteins, having enhanced water-solubility and storage stability.

Claims

1. Labelled boronic acid compound of formula ##STR24## (wherein V is a reporter moiety;

W² is a bond or an organic linker moiety;

W¹ is a *SO₂ NR², *CONR² or

*CH₂ N⊕

R² ₂ group bound at the *-marked atom to the phenyl ring;

R¹ is hydrogen or an electron withdrawing substituent group; and

each R² independently is hydrogen or an optionally hydroxylated and optionally C_1-6 -alkoxylated C_1-6 -alkyl group) and salts thereof.

2. Compounds as claimed in claim 1 wherein W¹ is a SO₂ NR² or CONR² group attached to the phenyl ring at the 4-position thereof.

3. Compounds as claimed in claim 1 wherein W¹ is a SO₂ NR² or CONR² group attached to the. phenyl ring at the 2, 3, 5 or 6-position thereof.

4. Compounds as claimed in claim 1 wherein W¹ is a CH₂ N⊕

R₂ ² group attached to the phenyl ring at the 3 or 5 position thereof.

5. Compounds as claimed in claim 1 wherein W¹ is a CH₂ N⊕

R₂ ² group attached to the phenyl ring at the 2 4 or 6-position thereof.

6. Compounds as claimed in claim 1 wherein R¹ denotes an SO₂ H, CO₂ H or NO₂ group attached at the 3 or 5 position of the phenyl ring.

7. Compounds as claimed in claim 1 wherein R¹ denotes an SO₂ H, CO₂ H or NO₂ group attached at the 2, 4 or 6-positions of the phenyl ring.

8. Compounds as claimed in claim 1 wherein W² is a group of formula IV

9. Compounds as claimed in claim 8 wherein W² is selected from the group consisting of:

--NH--CH₂ --CHOH--CH₂ --

--NH--CH₂ CH₂ --NH--CH₂ CH₂ --

--NH--CH₂ CH₂ --O--CH₂ CH₂ --

--NH--CH₂ CH₂ --

--NH--CH₂ CH₂ CH₂ --

--NH--CH₂ CH₂ CH₂ CH₂ --

--NH--CH₂ CH₂ CH₂ CH(COOH)--

NH--CH₂ CHOH--

--NH--CH₂ CH(COOH)--

--NH--CH₂ --NH--CH₂ --

--NH--CH₂ CH₂ CH₂ CH₂ CH₂ CH₂ --

--NH--CH₂ CH₂ CH₂ CH₂ CH₂ --

--NH--CH₂ --O-CH₂ --

--NH--CH₂ --O--CH₂ --O--CH₂ --

--NH--CH₂ CH₂ --O--CH₂ CH₂ --O--CH₂ CH₂ --

--NH--CH(COOH)CH₂ CH₂ --

--NH--CH(COOH)CH₂ CH₂ CH₂ CH₂

--NH--CH₂ CH(COOH)CH(COOH)--

--NH--CH₂ CHOHCHOH-- and

--NH CH₂ CH(CHO)CH(CHO)-- groups.

10. Compounds as claimed in claim 1 wherein V is a chromophore or fluorophore.

11. Compounds as claimed in claim 10 wherein V has an absorption maximum in the range 600-1000 nm.

12. Compounds as claimed in claim 10 wherein V is an azine, triarylmethine, phthalocyanine or cyanine dye.

13. Compounds as claimed in claim 12 wherein V is a xylene-cyanole dye.

14. Compounds as claimed in claim 1 being compounds of formula (V) ##STR25## where V and R² are as defined in claim 1, X³ is a CO or SO₂ group, and W² is a group of formula IV

15. Compounds as claimed in claim 1 being compounds of formula VI ##STR26## (where V, R¹ and W² are as defined in claim 1, and W³ is NHCO or SO₂ NH) and salts thereof.

16. Compounds as claimed in claim 1 being compounds of formula VII ##STR27## (where V, W² and R² are as defined in claim 1) and salts thereof.

17. Compound of formula VIII ##STR28## (where X², R¹, R³, n m and W¹ are as defined in claim 8 and X^1* is a reactive functional group) and salts thereof.