Synthesis and evaluation of [123I]labelled analogues of the partial inverse agonist Ro 15-4513 for the study of diazepam-insensitive benzodiazepine receptors

The imidazobenzodiazepines ethyl 8-iodo-5,6 dihydro-5-methyl-6-oxo-4H-imidazo[1,5a][1,4] benzodiazepine-3-carboxylate 1 and tert-butyl 8-iodo-5,6 dihydro-5-methyl-6-oxo-4H-imidazo [1,5a][1,4] benzodiazepine-3-carboxylate 2 were prepared to study the diazepam-insensitive (DI) benzodiazepine receptor (BZR) subtype. The [123I] analogues were prepared via iododestannylation reactions in radiochemical yields of 70-80% and a specific activity >2,500 Ci/mmol. The tert-butyl analogue [123I]-2 exhibited nanomolar affinity for BZRs in homogenate membranes of rat cerebellum with Kd values for the diazepam-sensitive (DS) and DI receptors of 3.18±0.58 and 13.55±2.72 nM, respectively. The Bmax for cerebellar DS and DI receptors were 1,276±195 and 518±26 fmol/mg protein, respectively