Synthesis of [123I]iodine labelled imidazo[1,2-b] pyridazines as potential probes for the study of peripheral benzodiazepine receptors using SPECT

Abstract

Abstract The pyridazines 3-acetamidomethyl-6-chloro-2-(4´-iodophenyl)imidazo[1,2-b]pyridazine 1 (IC50=1.6 nM) and 3-benzamidomethyl-6-iodo-2-(4´-t-butylphenyl)imidazo[1,2-b] pyridazine 2 (IC50=4.2 nM), are high affinity and selective ligands for the Peripheral Benzodiazepine Receptors (PBR) compared to the Central Benzodiazepine counterparts. The [123I] 1 and [123I] 2 labelled analogues of these compounds were subsequently synthesised for the potential study of the PBR in vivo using SPECT. Radioiodination of [123I] 1 was achieved by iododestannylation of the corresponding tributyl tin precursor with Na[ 123I] in the presence of peracetic acid or chloramine-T and the product isolated by C-18 RP HPLC. Radioiodination of [123I] 2 was achieved by copper assisted bromine [123I]iodine exchange of the corresponding bromo precursor in the presence of acetic acid and sodium bisulfate as reducing agent at 200 °C. Purification of the crude products were achieved by semi-preparative C-18 RP HPLC to give the products in radiochemical yields >90%. The products were obtained in >97% chemical and radiochemical purity and with specific activities >180 GBq/μmol.