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.
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 cases greater than 99%.
Halldin
C
C
Karolinska Pharmacy, Stockholm, Sweden.
Stone-Elander
S
S
Thorell
J O
JO
Persson
A
A
Sedvall
G
G
D002250:Carbon Radioisotopes; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D011963:Receptors, GABA-A / Q000032:analysis*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil; C058027:Ro 15-3890