11C-labelling of Ro 15-1788 in two different positions, and also 11C-labelling of its main metabolite Ro 15-3890, for PET studies of benzodiazepine receptors

Abstract

The benzodiazepine receptor antagonist Ro 15-1788 has been labelled with 11C in two different positions ([methyl- 11C]Ro 15-1788 ( I) and [ethyl- 11C]Ro 15-1788 ( II)). Product I was prepared by N-alkylation of the desmethyl compound (Ro 15-5528) with [ 11C]methyl iodide and product II was prepared by esterification of the desethyl compound (Ro 15-3890) with [ 11C]ethyl iodide. Ro 15-3890, the main metabolic product of Ro 15-1788, was labelled by two synthetic routes. In route A, [methyl- 11C]Ro 15-3890 ( III) was prepared by N-alkylation of the corresponding desmethyl compound (Ro 15-6877) with [ 11C]methyl iodide. In route B, III was prepared by a subsequent hydrolysis of I. The radiochemical yields were on the order of 15–60% (EOB) with an overall synthesis time of 40–50 min. Compounds I, II and III were isolated by semi-preparative HPLC and the radiochemical purity was in all case >99%.