Michael P. Groziak

7.alpha.-Substituted derivatives of androstenedione as inhibitors of estrogen biosynthesis

In an effort to obtain more information on the structure-activity relationship among the 7 alpha-(phenylthio)androstenedione inhibitors of the enzyme aromatase, a series of compounds containing both electron-donating and electron-withdrawing ring substituents was synthesized and tested for aromatase inhibitory activity. No linear correlation between substituent electronic effects and inhibitory activity was observed. The halogen-containing compounds, particularly 8, appeared to be quite potent inhibitors. The 125I analogue of 8 was synthesized in order to evaluate the possibility of side-chain elimination under the assay conditions. Approximately 90% of [125I]-8 remained intact for up to 1 h under assay conditions.

Radioiodination via isotope exchange in pivalic acid

A variety of benzoic and aryl aliphatic mono and polyiodinated acids and esters (sterol, triglyceride) were radioiodinated in 55–99% radiochemical yield by isotope exchange with Na 125I in a melt of pivalic acid. In general, the reaction was complete in 1 h at 155°C with little or no substrate decompostion. High specific activity studies afforded 125I-labeled iopanoic acid with a specific activity of over 700 Ci/mmol.

Esters of iopanoic acid as liver-specific CT contrast agents: biodistribution and CT evaluation

The synthesis and preliminary biodistribution data for a series of sterol-like esters of iopanoic acid having potential value as liver-specific CT contrast agents are described. Structural modification of the sterol portion of the iopanoate ester afforded a group of compounds that displayed tissue specificity similar to chqlesteryl iopanoate, the prototype ester of this series, but were rapidly cleared from the target tissues after hydrolysis. From the biodistribution data, the most promising of these agents, pregnenolone iopanoate (PI), was evaluated by CT in rabbits receiving a radiologic dose equivalent to 30 mg I/kg. The hepatic parenchyma was enhanced within 2 h of infusion to a maximal level of 31 HU above precontrast values. Hepatic CT attenuation returned to normal within 24 h. However, CT performed after PI infusion into Vx2 tumor-bearing rabbits failed to provide superior images compared with those acquired following bolus administration of urographic contrast.