Relative activities of several 3'- and 3':5'-alkyl and aryl thyromimetic agents

¹ Research and Development Division, Smith Kline & French Laboratories, Philadelphia, Pennsylvania

The biological activity of several 3:5-diiodo-3'- and 3':5'-alkyl and arylthyronines as well as of some 3:5-diiodo-3'-isopropylthyroacetic acid analogues was determined following their subcutaneous administration to adult male rats. l(+) 3:5:3'-triiodothyronine (l-triiodothyronine) was used as the reference compound. l(+) 3:5-Diiodo-3'-isopropylthyronine was the only compound in this series found to be more active than l-triiodothyronine in all of the assays that were performed. It exhibited twice the calorigenic, 1.3 times the cholesterol-lowering, 1.8 times the antigoitrogenic, and 1.4 times the heart weight-increasing activity of the reference agent. This is the first thyromimetic substance reported to be more active in rats than the endogenous thyroid hormones. Each experiment consisted of injecting at least four doses of the agent to be assayed as well as of l-triiodothyronine to different groups of rats. The resulting data were evaluated statistically. Photographs of Courtald atomic models of several alkyl thyronines are presented for the purpose of indicating the possible importance of the relative "bulk" of the alkyl constituents compared to that of the iodine atom in the 3'-position.

Key Words: 3'-isopropyl thyromimetic agents • analogues of triiodothyronine • potent thyromimetic agents • biological activity of thyromimetic agents • thyroid metabolism

Submitted on March 6, 1963