Structural determinants of selective thyromimetics

Hikari A I Yoshihara, James W. Apriletti, John D. Baxter, Thomas (Tom) Scanlan

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The thyromimetic GC-1 shows a preference for binding the β form of the thyroid hormone receptor (TR). GC-1 was designed as an analogue of the thyromimetic DIMIT, which has a lower affinity for TR and is not selective. GC-1 has a methylene group linking its two aromatic rings and an oxyacetic acid polar side chain, while DIMIT has an ether oxygen linking its aromatic rings and an L-alanine polar side chain. The structural features of GC-1 that confer its greater affinity and selectivity compared to DIMIT were analyzed with the preparation of analogues that bear only one of their two different structural features. The analogue of GC-1 with a biaryl ether has selectivity comparable to that of GC-1, while the analogue of DIMIT with a methylene group linking its aromatic rings is only slightly selective. These results demonstrate that the oxyacetic acid side chain of GC-1 is critical in conferring TR-β selectivity.

Original languageEnglish (US)
Pages (from-to)3152-3161
Number of pages10
JournalJournal of Medicinal Chemistry
Volume46
Issue number14
DOIs
StatePublished - Jul 3 2003
Externally publishedYes

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3,5-dimethyl-3'-isopropyl-L-thyronine
Thyroid Hormone Receptors
Ether
Acids
GC 1 compound
Alanine
Oxygen

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Structural determinants of selective thyromimetics. / Yoshihara, Hikari A I; Apriletti, James W.; Baxter, John D.; Scanlan, Thomas (Tom).

In: Journal of Medicinal Chemistry, Vol. 46, No. 14, 03.07.2003, p. 3152-3161.

Research output: Contribution to journalArticle

Yoshihara, HAI, Apriletti, JW, Baxter, JD & Scanlan, TT 2003, 'Structural determinants of selective thyromimetics', Journal of Medicinal Chemistry, vol. 46, no. 14, pp. 3152-3161. https://doi.org/10.1021/jm0301181
Yoshihara, Hikari A I ; Apriletti, James W. ; Baxter, John D. ; Scanlan, Thomas (Tom). / Structural determinants of selective thyromimetics. In: Journal of Medicinal Chemistry. 2003 ; Vol. 46, No. 14. pp. 3152-3161.
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