Synthesis and biodistribution of radioiodinated nicotine analogs

Four 125I‐labelled nicotine analogs were synthesized: 3‐(methylpropylaminomethyl)‐, 3‐(diethylaminomethyl)‐, 3‐(isopropylaminomethyl)‐, and 3‐(diisopropylaminomethyl)‐5‐[125I]‐iodopyridines. 5‐Bromonicotinic acid was acylated with thionyl chloride and then reacted with the appropriate primary and secondary amines to give the corresponding amides which were reduced with diborane to the desirable amines. Radioiodination was done by halogen exchange. Biodistribution studies in rats, showed that all four labelled compounds were rapidly taken up by the brain and the adrenal gland. This was followed by rapid washout of the compounds from these orrans. The most promising of these compounds, 3‐(diisopropylaminomethyl)‐5‐[125I]‐iodopyridine, showed a brain‐to‐blood ratio of 6.0:1 and an adrenal‐to‐blood ratio of 35.9:1 at 2 minutes post administration. In vitro correlation studies showed that brain uptake of these compounds depends on both protein binding and lipophilicity, whereas adrenal uptake depends only on lipophilicity.