Thyroxine analogs and reagents for thyroid hormone assays

• US 4,741,897 A
• Filed: 07/08/1986
• Issued: 05/03/1988
• Est. Priority Date: 07/08/1986
• Status: Expired due to Term

• Current Assignee: Dade Behring, Inc. (Siemens AG)
• Original Assignee: Baxter Travenol
• Inventors: Burns, Christine, Andrews, Judith, Quick, James
• Primary Examiner(s): Schwartz, Richard A.
• Application Number:
  US06/883,241
• Time in Patent Office: 665 Days
• Field of Search: 424/1.1, 436/500, 435/7, 548/342, 548/344, 548/335
• US Class Current: 436/500
• CPC Class Codes: G01N 33/78 Thyroid gland hormones , e.g. T3, T4, TBH, TBG or their receptors

Abstract

The present invention relates to new compounds of the general formula: ##STR1## where X is iodine or hydrogen; A is a linking portion; and R is an iodinatable aryl or heteroaryl group having electron donating substituents. These compounds are useful precursors to the iodinated thyroid hormones for radioimmunoassay determination of thyroid hormones in biological fluids.

Claims

1. A compound of the formula:

##STR20## wherein X is iodine or hydrogen;

R₁ is ##STR21## where n₁ is an integer from 0 to about 4, n is an integer from 0 to about 5, and R₄ is hydrogen, methyl, ethyl, or propyl;

R₂ is ##STR22## where n₂ is an integer from about 2 to about 6, n₃ is an integer from about 0 to about 2, and n₄ is an integer from about 4 to about 6; and

R₃ is ##STR23## where R₅ is hydrogen, CO₂ R₄ or --NH₂ and R₆ is ##STR24##

2. The compound of claim 1 wherein R₁ is ##STR25## R₂ is ##STR26## where R₅ is --CO₂ R₄ or hydrogen.

3. The compound of claim 2 wherein R₂ is ##STR27##

4. The compound of claim 2 wherein R₁ is --CH₂ --CH₂ and R₂ is ##STR28##

5. The compound of claim 4 wherein R₃ is --NH--CH₂ --CH₂ --R₆.

6. A reagent for determining thyroxine or triiodothyroxine in a biological fluid, said reagent comprising an antibody capable of immunologically reacting with said thyroxine or triiodothyroxine and a labelled ligand capable of binding to said antibody, said labelled ligand having the formula ##STR29## wherein X is iodine or hydrogen;

R₁ is ##STR30## where n₁ an integer from 0 to about 4, n is an integer from 0 to about 5, and R₄ is hydrogen, methyl, ethyl, or propyl;

R₂ is ##STR31## where n₂ is an integer from about 2 to about 6, n₃ is an integer from about 0 to about 2, and n₄ is an integer from about 4 to about 6; and

R₃ is ##STR32## where R₅ is hydrogen, CO₂ R₄ or --NH₂ and R₆ is ##STR33## wherein R₆ is labelled with radioactive iodine.

7. The reagent of claim 6 wherein R₆ is ##STR34##

8. The reagent of claim 7 wherein R₁ is ##STR35## where n is 1 or 2;

R₂ is ##STR36## and R₃ is --NHCH₂ CH₂ --R₆.

9. The reagent of claim 8 wherein R₁ is --CH₂ --CH₂ --;

and R₂ is ##STR37##

10. The reagent of claim 8 wherein R₁ is ##STR38## and R₂ is ##STR39##