Thyroxine Analogues

Three novel thyroid hormone analogues: alpha-methyl-3,5,3'-triiodothyroacetic acid, alpha-methyl-3,5,3'-triiodothyropropionic acid, and alpha-methyl-3,5,3',5'-tetraiodothyropropionic acid were synthesized. The hepatic thyroid receptor affinity of these analogues was compared to that other available thyroid analogues. The ability of these compounds to increase the activity of two hepatic enzymes and to lower blood cholesterol was compared to that of L-triiodothyronine. alpha-Methyl-3,5,3'-triiodothyroacetic acid was shown to have less nuclear binding affinity, less enzyme inducing ability, but more blood cholesterol lowering ability than triiodothyroacetic acid. alpha-Methyl-3,5,3',5'-tetraiodothyropropionic acid showed less nuclear binding affinity and less enzyme-inducing activity than alpha-methyl-3,5,3'-triiodothyropropionic acid.

Section: -Hydroxy-35-diiodo-a-methylphenylacetic Acid (Iii)mentioning

confidence: 99%

.alpha.-Methylated analogs of triiodothyroalkanoic acids: synthesis and biological activity

Zenker¹,

Ae²,

Ls³

1992

“…Found: C, 67.OS: II.VG7: X, 4.02. p- (2,.-To a solution of 30.1 g (0.0(1 mole) of 3,5-<liiodo-4-i/)-methoxyphenoxy)-l-nitm-benzeno2,3 in 120 mi of pyridine was added IS.5 g of cuprous cyanide. Vigorous stirring was required to keep the viscous mass mobile.…”

Section: Jorgensen Andmentioning

confidence: 99%

Thyromimetics. VII. Isopropyl Analogs of Thyroid Hormones

Blank¹,

Pfeiffer²

1967

Attempts were made to prepare thyroidal hormones with isopropyl groups in place of the iodine atoms. 3,3'-Diisopropyl-and 3,3',5'-triisopropyl-DL-thyronines (I and III) were prepared successfully. The more desirable isopropyl analogs of 3,3',5-triiodothyronine (l-Ts) and thyroxine (II and IV) were not obtained. A number of possible routes to II and IV were studied and are described. Ill was tested and found inactive as a hypocholesteremic or antigoitrogenic agent and as an inhibitor of L-Ts.

“…From eq 44 it is evident that eq 41, 42, and 43 are without any significance in predicting differences in biological activity among the trisubstituted hydrazides 52-66 and 68-71; eq 41 and 43 are chance correlations. 39 This example demonstrates that care must be taken in the selection of compounds for Hansch analysis; compounds with different structures and very different activities (such as compounds 50 and 51) should be excluded if they have such a great influence on the overall result (note that Tute40 came to a similar conclusion discussing a theoretical example, ref 40, pp [41][42].…”

mentioning

confidence: 98%

Quantitative structure-activity relationships. 2. A mixed approach, based on Hansch and Free-Wilson analysis

Kubinyi¹

1976

Based on the theoretical and numerical equivalence of Hansch's linear multiple regression model and the modified Free-Wilson model a mixed approach is developed. The mixed approach is a combination of both models which makes use of the advantages of each model and widens the applicability of Hansch and Free-Wilson analysis. The Free-Wilson approach now is applicable also in the case of parabolic dependence of biological activity on a particular physical property, e.g., log P or pi. A rational explanation is given for the use of dummy variables in Hansch equations and the derivation of Hansch correlations for de novo group contributions obtained from Free-Wilson analysis. Some examples illustrate the mixed approach and demonstrate its usefulness to establish biologically meaningful structure-activity relationships.