Synthesis and evaluation of radioiodinated derivatives of 1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(4-iodophenyl)-alpha- phenylacetate as potential radiopharmaceuticals.

Two derivatives of (RS)-1-azabicyclo(2.2.2)oct-3-yl (RS)-alpha-hydroxy-alpha-(4-iodophenyl)-alpha-phenylacetate (1a) and three partially resolved (R)- or (S)-1-azabicyclo(2.2.2)oct-3-yl (RS)-alpha-hydroxy-alpha-(4-iodophenyl)-alpha-phenylacetates labeled with no carrier added iodine-125 (1b, 18, and 19) and iodine-123 (1c and 18a) were synthesized by the Wallach triazene approach. We have found that this approach is necessary to obtain no carrier added labeling and gives far better results than the direct electrophilic iodination. The obtained yields were 7 to 18% when using iodine-123 (yield dependent on the source of iodide) and up to 17% for iodine-123 (yield dependent on the source of iodide) and up to 17% for iodine-125 labeled compounds. Our preliminary distribution studies indicate that 1b localizes in the organs known to have a large concentration of muscarinic receptors and that this localization is due to binding to those receptors.