Peptide-based compounds

A compound and chelate technology, applied in the field of new peptide-based compounds, can solve the problem of high background noise

Inactive Publication Date: 2009-09-16
GE HEALTHCARE AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, biodistribution studies using whole-body autoradiographic imaging have shown that 125 I-labeled peptides have very fast blood clearance, and the prominent hepatobiliary secretory pathway results in high background noise

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0054] Compound 1:

[0055]

[0056] Compound 2: Vehicle

[0057]

[0058] Compound 3: Examples of V-L-R Compounds of Formula I

[0059]

[0060] Compound 4: Example of a compound of formula II

[0061]

[0062] Compound 5: able to connect, for example 99m The formula of Tc? compound example

[0063]

[0064] In most cases, it is preferred that the amino acid in Vehicle V is in the L-form. However, in some embodiments of the invention, one, two, three or more amino acids in vehicle V are preferably in the D-form. The presence of this D-form amino acid has an important effect on the serum stability of the vehicle. In this regard, particular attention is paid to the X 1 A vehicle with D-tyrosine at the site.

[0065] The present invention also provides a pharmaceutical composition comprising an effective amount (for example, an amount effective for enhancing image contrast and / or treatment in vivo imaging) of a compound of general formula (I) or an acid ad...

Embodiment 1

[0144] Embodiment 1: the synthesis of compound 1

[0145]

[0146] Synthesis of Technetium Chelate-Pn216

[0147] a) Chloro-nitroso intermediate (3-chloro-3-methyl-2-nitrosobutane)

[0148] A mixture of 2-methylbut-2-ene (18.5ml) and isoamyl nitrate (19.5ml) was stirred, cooled to -10°C and concentrated hydrochloric acid (17.5ml) was added carefully keeping the temperature below 0°C. The reaction mixture was stirred at this temperature for 30 minutes. The formed precipitate was collected by filtration, washed with 4 x 5 ml ethanol (-20°C) and dried in vacuo to give 3-chloro-3-methyl-2-nitrosobutane as a white solid.

[0149] b) Pn216-(3,3,11,11-tetramethyl-7-aminoethyl-4.7,10-triazatridecane -2,12-diketodioxime)

[0150]To a solution of tris-(2-aminoethyl)amine in acetonitrile (20ml) was added sodium bicarbonate (2.2g, 26mmol). A solution of 3-chloro-3-methyl-2-nitrosobutane (1.8 g, 13 mmol) in dry acetonitrile was added slowly at 0°C. The reaction mixture was ...

Embodiment 2

[0172] Example 2: [Cys 2-8，8-10 ]analog

[0173] a) Synthesis of ClCH 2 CO-Lys-Asp-Cys-Arg-Gly-Asp-Cys(tBu)-Phe- Cys(tBu)-Gly-Gly-OH

[0174]

[0175] Peptides were synthesized on an ABI 433A automated peptide synthesizer using a 1 mmol amino acid cartridge in the order of 0.25 mmol using Fmoc-Gly wang resin (NoVabiochem) as starting material. Amino acids were preactivated with HBTU prior to coupling. Final N-terminal chloroacetylation was performed using chloroacetic anhydride in DMF for 30 minutes.

[0176] Containing TIS (5%), H 2 Both peptide and side chain protecting groups (except tBu) were removed from the resin in TFA of O (5%) and phenol (2.5%) for 2 hours.

[0177] After the above treatment, 260 mg of crude peptide was obtained (analytical HPLC: gradient, 5-50% B over 10 minutes, where A=H 2 O / 0.1%TFA and B=CH 3 CN / 0.1% TFA; column, Phenomenex Luna 3μC18 (2) 50 x 4.6mm; flow rate, 2ml / min, detection, UV214nm; product retention time, 6.5 minute...

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Abstract

This invention relates to new peptide-based compounds and their use in therapeutically effective treatments as well as for diagnostic imaging techniques. More specifically the invention relates to the use of such peptide-based compounds used as targeting vectors that bind to receptors associated with angiogenesis, in particular the alphavbeta3 integrin receptor. Such contrast agents may thus be used for diagnosis of for example malignant diseases, heart diseases, inflammation-related diseases, rheumatoid arthritis and Kaposi's sarcoma. Moreover such compounds may also be used in therapeutic treatment of these diseases.

Description

[0001] This application is a divisional application submitted based on the application date of September 25, 2001 and application number 01816130.8. technical field [0002] The present invention relates to novel peptidyl compounds and their use in medically effective treatments and in diagnostic imaging techniques. More particularly, the present invention relates to the use of said peptidyl compounds as targeting mediators for the binding of receptors associated with angiogenesis, especially αvβ3 integrin receptors. Such contrast agents can be used in the diagnosis of, for example, malignancies, cardiac diseases, diseases associated with inflammation, rheumatoid arthritis and Kaposi's sarcoma. And the compounds can also be used in the treatment of these diseases. Background technique [0003] New blood vessels can form by two different mechanisms: angiogenesis or angiogenesis. Angiogenesis is the formation of new blood vessels by branching from existing blood vessels. Th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K51/00A61K49/00A61K38/08A61K38/00A61K38/12A61K38/14A61P1/02A61P1/04A61P9/00A61P9/10A61P15/08A61P17/06A61P17/12A61P19/02A61P27/02A61P29/00A61P35/00A61P43/00C07KC07K7/00C07K7/08C07K9/00C07K14/00C07K14/705
CPCC07K14/70546C07K7/06A61K51/082A61P1/02A61P1/04A61P15/08A61P17/06A61P17/12A61P19/02A61P27/02A61P29/00A61P35/00A61P43/00A61P9/00A61P9/10C07K7/00
Inventor A·库斯伯特森
Owner GE HEALTHCARE AS
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