Potential cerebral perfusion agents. Synthesis and evaluation of new radioiodinated barbituric acid analogs

Article abstract of DOI:10.1002/jhet.5570200446

Two new ¹²⁵I-labeled barbituric acid analogs, 5-ethyl-5-(E-1-iodo-1-penten-5-yl)-2-thiobarbituric acid (4) and 5-ethyl-5-(m-iodophenyl)barbituric acid (7), have been prepared and evaluated in rats as potential cerebral perfusion agents. Annulation of 2-ethyl-2-(E-1-iodo-1-penten-5-yl)malonate (3) with thiourea in the presence of sodium ethoxide gave the 5-ethyl-5-(E-1-iodo-1-penten-5-yl)-2-thiobarbituric acid (4). Diethyl 2-ethyl-2-phenylmalonate was treated with thallium(III) trifluoroacetate followed by addition of aqueous potassium iodide to provide diethyl 2-ethyl-2-(m-iodophenyl)malonate (10). The malonic ester derivative 10 was condensed with urea in the presence of sodium hydride to give the desired 5-ethyl-5-(m-iodophenyl)butyric acid (7), and a decarbethoxylation product, 2-(,-iodophenyl)butyric acid (11). Iodine-125-labeled 4 and 7 were synthesized in the same manner and the tissue distribution of these new agents evaluated in rats. Both [¹²⁵I] 4 and [¹²⁵I] 7 showed high brain uptake. Significant in vivo deiodination was detected with [¹²⁵I] 4 whereas [¹²⁵I] 7 was found to be stable to deiodination.