Synthesis and evaluation of [I-123]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-imid azo[ 1,5a][1,4] benzodiazepine-3-carboxylate 1 and tert-butyl 8-iodo-5,6 di hydro-5 -methyl 6-oxo 4H-imidazo [1,5a][1,4] benzodiazepine-3-carboxylate 2 were prepared to study the diazepam-insensitive (DI) benzodiazepine recept or (BZR) subtype. The [I-123] analogues were prepared via iododestannylatio n reactions in radiochemical yields of 70-80% and a specific activity > 2,5 00 Ci/mmol. The tert butyl analogue [I-123]-2 exhibited nanomolar affinity for BZRs in homogenate membranes of rat cerebellum with Kd values for the d iazepam sensitive (DS) and DI receptors of 3.18 +/- 0.58 and 13.55 +/- 2.72 nM, respectively. The B-max for cerebellar DS and DI receptors were 1,276 +/- 195 and 518 +/- 26 fmol/mg protein, respectively. NUCL MED BIOL 26;6:64 1-649, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.