Derivatives of endogenous mediators, their salts, method of preparation, applications and compositions in which they are present

• US 5,298,491 A
• Filed: 05/13/1991
• Issued: 03/29/1994
• Est. Priority Date: 05/15/1990
• Status: Expired due to Term

• Current Assignee: Immunotech (Danaher Corporation)
• Original Assignee: Immunotech (Danaher Corporation)
• Inventors: Chauveau, Jacques, Morel, Anne, Segu, Louis, Delaage, Michel
• Primary Examiner(s): Lee, Mary C.
• Assistant Examiner(s): McKane, Joseph K.
• Application Number:
  US07/699,027
• Time in Patent Office: 1,051 Days
• Field of Search: 548/504, 252/182.11, 514/17, 514/18, 514/19, 514/415, 435/7.1, 435/7.9, 436/547, 436/164, 562/451, 530/412
• US Class Current: 514/9.7
• CPC Class Codes: C07D 209/16 Tryptamines
• CPC Class Codes: G01N 33/78 Thyroid gland hormones , e.g. T3, T4, TBH, TBG or their receptors

Abstract

Derivatives of biologically active molecules containing a primary amine group and a hydroxylated nucleus, and their addition salts with mineral or organic acids, having general formula I:

R'"'"'R"N--A--B--O--CH.sub.2 --CO--NH--R                       (I)

A=linear or branched C₁ -C₅ alkylene;

B=C₄ -C₁₀ aromatic nucleus with optional heteroatom, or=group --B₁ --X--B₂ --, wherein X=O or C₁ -C₄ alkylene;

--NH--R=amine residue or alcohol residue; and

R'"'"', R"=C₁ -C₅ alkyl, H or hydrophobic radical, and their addition salts with mineral or organic acids, method of preparation, applications, especially to visualization, purification, the preparation of antibodies and the assay of the total hormone, and as drugs, compositions in which they are present and analytical kits.

Claims

1. A dimer of the formula:

space="preserve" listing-type="equation">R'"'"'R"N--A--B--O--CH.sub.2 --CO--NH--R--NH--CO--CH.sub.2 --O--B--A--N--R'"'"'R"(I'"'"')

wherein

A is a linear or branched alkylene chain of 1 to 5 carbon atoms;

B is an optionally substituted aromatic nucleus of 6 to 10 carbon atoms and optionally a heteroatom;

R is an amino acid or a polypeptide consisting of at most 5 amino acids, or an amide thereof, or an addition salt thereof with mineral or organic acid; and

R'"'"' and R" are each an alkyl radical of 1 to 5 carbon atoms or a hydrogen atoms, or an addition salt thereof with a mineral or organic acid.

2. A derivative of a biologically active molecule containing a primary amine group and a hydroxylated nucleus, or an addition salt thereof with a mineral or organic acid, of the formula I:

space="preserve" listing-type="equation">[R'"'"'R"N--A--B--O--CH.sub.2 --CO].sub.n R.sub.1 (I)

n is an integer from 1 to 10;

A is a linear or branched alkylene chain of 1 to 5 carbon atoms;

B is an optionally substituted aromatic nucleus of 6 to 10 carbon atoms and ptionally a heteroatom;

R₁ is an amino acid or a peptide of 2 to 10 amino acids or an amide thereof; and

R'"'"' and R" are each an alkyl radical of 1 to 5 carbon atoms or a hydrogen atom, or an addition salt thereof with a mineral or organic acid.

3. A compound according to claim 2 wherein B is indole having an halogen substituent selected from the group consisting of chlorine, bromine and iodine.

4. A derivative of formula (I) as defined in claim 2, or an addition salt thereof with a mineral or organic acid, wherein B is a phenyl or indole nucleus.

5. A derivative according to claim 2, wherein R'"'"' and R" are alinear or branched alkyl radical containing from 1 to 5 carbon atoms and A is a radial --CH₂ --CH₂ --, or an addition salt thereof with a mineral or organic acid.

7. A pharmaceutical composition containing, as the active principle, at least one compound as defined in claim 2.

8. A pharmaceutical composition containing, as the active principle, at least one compound as defined in claim 4.

10. An analytical kit for assaying mediators and derivatives thereof, containing at least one derivative according to claim 2.

11. A compound according to claim 4, wherein R'"'"' and R" are a linear or branched alkyl containing from 1 to 5 carbon atoms and A is --CH₂ --CH₂ --, or an addition salt with an acid.

12. An analytical kit for assaying mediators and derivatives thereof, containing a compund according to claim 4.

13. Tryptamine 5-O carboxymethyl tyrosylglycinamide or an addition salt thereof with a mineral or organic acid, in accordance with claim 2.

14. Tryptamine 5-O carboxymethylglycyliodotyrosinamide or an addition salt thereof with a mineral or organic acid, in accordance with claim 2.

16. A compound according to claim 2, wherein R₁ is a low molecular weight group of the formula --NHR wherein R is an amino acid or a polypeptide containing 2-10 amino acids.

18. A compound according to claim 12 wherein B is bromo substituted indole.

6. Tryptamine-5-O-carboxymethylglycyltyrosinamide or its addition salt with a mineral or organic acid.

9. A pharmaceutical composition containing, as the active principle, at least one compound as defined in claim 6.

15. Tryptamine 5-O carboxymethyl iodotyrosylglycinamide or an addition salt thereof with a mineral or organic acid, in accordance with claim s.

17. A compound selected from the group consisting of 5-O-carboxymethyltryptamine and conjugates thereof with glycyl-tyrosinamide, histamine, Tyr-Gly, Gly-Tyr, Gly-Gly, Gly-Cys, Gly-TyrNH₂, Tyr-GlyNH₂, and iodinated derivatives of said conjugates containing histamine or tyrosine;

and Tryptamine-5-O-carboxymethylglycyltyrosinamide.