Document Detail

Structural determinants of selective thyromimetics.
MedLine Citation:
PMID:  12825953     Owner:  NLM     Status:  MEDLINE    
The thyromimetic GC-1 shows a preference for binding the beta 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-beta selectivity.
Hikari A I Yoshihara; James W Apriletti; John D Baxter; Thomas S Scanlan
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  46     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-06-26     Completed Date:  2003-08-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3152-61     Citation Subset:  IM    
Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143-2280, USA.
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MeSH Terms
Acetic Acids / chemistry*
Binding, Competitive
Phenols / chemistry*
Structure-Activity Relationship
Thyroid Hormone Receptors beta / chemistry*,  isolation & purification
Grant Support
Reg. No./Substance:
0/Acetic Acids; 0/GC 1 compound; 0/Ligands; 0/Phenols; 0/Thyroid Hormone Receptors beta

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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