Metabolic and Cardiac Responses to Thyroxine Analogs

Publisher Website
Google Scholar
Abstract
The present study has utilized 2 physiological functions known to be affected by thyroid status, basal O2 consumption and resting heart rate, to evaluate analogs of T4 primarily involving alterations in the iodohydroxyl- diphenyl ether portion of the T4 molecule. The following generalizations can be made: (a) there should be halogens, either I or Br, at both carbons 3 and 5 on the α-ring; (b) on the β-ring, substitution at 5′ decreases activity, substitution at 3′ is necessary, but bulk, i.e., the isopropyl group or the second aromatic ring of the naphthyl derivative, is at least as important as electronic character (isopropyl substitution imparts greater activity than iodine); (c) substitution at 4′ and linkage between the α- and β-rings should be capable of undergoing coordinated electronic shifts, as, for instance, into a quinone or quinoneimine, although not all 4′-NH2 conpounds are effective. In agreement with current concepts, 3′-isopropyl-3,5-diiodothyronine has been found to be the most active of all thyroxine analogs and derivations, being at least 50% more potent than 3,5,3′-triiodothyronine. (Endocrinology76: 115, 1965)

This publication has 0 references indexed in Scilit: