Efficient Synthesis of a New Potential Chelating Agent for Radioimmunotherapy

Abstract

The synthesis of a new rigid analogue of cyclohexyl-TTHA, an efficient lanthanide ligand, as well, as the first complexation trials are reported. This polyaminopolycarboxylic acid, Ph-DTHA 1, was obtained in five steps from phenylenediamine as starting product. The key intermediate was phenylenediethylenetetraamine 4, which after alkylation and hydrolysis gave the expected compound 1 with ten coordination centers.

Key words

ligands - polyaminopolycarboxylic acids - radioimmunotherapy - complexes - radionuclides

References

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15

Spectrum data of compound 1: IR (KBr): 3419, 2970, 1733, 1635, 1418, 1256 cm^-1; ¹H NMR (200 MHz, D₂O): δ = 3.49 [4 H, m, 2 × NCH₂CH ₂N(CH₂CO₂H)₂], 3.69 (4 H, m, 2 × NCH ₂CH₂N(CH₂CO₂H)₂), 4.09 [4 H, s, 2 × N(CH ₂CO₂H)], 4.19 [8 H, s, 2 × N(CH ₂ CO₂H)₂], 7.13 (4 H, m, CHar);
¹³C NMR (50 MHz, D₂O): δ = 50.4 [2 × NCH₂ CH₂N(CH₂CO₂H)₂], 56.5 [2 × NCH₂CH₂N(CH₂CO₂H)₂], 57.3 [2 × N(CH₂CO₂H)], 58.5 [2 × N(CH₂CO₂H)₂], 125.7 [2 × CHar], 128.8 [2 × CHar], 145.0 [2 × Car], 171.9 [4 × N(CH₂ CO₂H)₂], 178.2 [2 × N(CH₂ CO₂H)]; MS (ES+): = 543.1 (M + H⁺), 565.1 (M + Na⁺); mp >300 °C.