Linked Life Data

16451067

Source:http://linkedlifedata.com/resource/pubmed/id/16451067

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-2-2
pubmed:abstractText
The synthesis of a series of novel 1-[(benzofuran-2-yl)phenylmethyl]-pyridine, -imidazole, and -triazole derivatives is described. All the compounds were evaluated in vitro for inhibitory activity against aromatase (P450(AROM), CYP19), using human placental microsomes. The 6-methoxy- and 6-hydroxy-substituted benzofuran derivatives were shown to be potent CYP19 inhibitors (IC(50) = 0.01-1.46 microM) with activity greater than that observed for the unsubstituted parent compounds and inhibitory activity comparable with or greater than the reference compound arimidex (IC(50) = 0.6 microM). Six of the benzofuran derivatives were subjected to in vitro cytotoxicity assays, using rat liver hepatocytes with cytotoxicity determined from alteration in cell morphology and lactate dehydrogenase enzyme retention over a period of 24 h, and selectivity (CYP17, 17beta-HSD types 1 and 3, CYP24, and CYP26) determination; negligible inhibitory activity was observed, suggesting a good selectivity for CYP19. The pyridine benzofuran 4a containing the 4-fluorophenyl group was the most promising (IC(50) = 44 nM; LC(50) >100 microM) compared with arimidex (IC(50) = 600 nM; LC(50) > 200 microM).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1016-22
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Potent CYP19 (aromatase) 1-[(benzofuran-2-yl)(phenylmethyl)pyridine, -imidazole, and -triazole inhibitors: synthesis and biological evaluation.
pubmed:affiliation
Medicinal Chemistry, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, Wales, U.K.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't