alpha-Methylated analogues of triiodothyroalkanoic acids: synthesis and biological activity.
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.
Zenker
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N
Department of Biomedicinal Chemistry, School of Pharmacy, University of Maryland, Baltimore 21201.
Ekpe
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AE
Hubbard
L S
LS
D000818:Animals; D002784:Cholesterol / Q000097:blood; D004790:Enzyme Induction / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis; D008291:Malate Dehydrogenase / Q000096:biosynthesis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011988:Receptors, Thyroid Hormone / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013963:Thyroid Hormones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D014284:Triiodothyronine; D002784:Cholesterol; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase