Linked Life Data

10346938

Source:http://linkedlifedata.com/resource/pubmed/id/10346938

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1999-6-10
pubmed:abstractText
A series of substituted 3-amino-5-phenoxythiophenes was synthesized starting from malodinitrile and carbon disulfide. The resulting dicyanoketenedithiolate reacts via Thorpe-Dieckmann cyclization with halogen methanes bearing electron-withdrawing groups to give thiophene-2-thiolates, which can be transformed into 3-amino-5-(methylsulfonyl)thiophene-4-carbonitriles. Replacement of the methylsulfonyl groups by substituted phenolates provides the substituted 3-amino-5-phenoxythiophenes. Some of the derivatives show a considerable inhibitory potency for the L-T3 uptake in inhibition studies on human HepG2 hepatoma cells with maximum values of about 60% at a dose of 10(-5) M for the most potent 2-benzoyl derivatives. The structure of the phenoxythiophenes fits well into a general concept derived for other classes of L-T3 uptake inhibitors, which postulates an angular and perpendicular orientation of the ring systems in these compounds as a prerequisite for an inhibitory potency. Docking studies for the phenoxythiophenes with transthyretin as a receptor model show their preferred attack at the L-T4/L-T3 binding channel.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1849-54
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
3-Amino-5-phenoxythiophenes: syntheses and structure-function studies of a novel class of inhibitors of cellular L-triiodothyronine uptake.
pubmed:affiliation
Institute of Pharmacy, Faculty of Biosciences, Pharmacy, and Psychology, University of Leipzig, Brüderstrasse 34, D-04103 Leipzig, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't