Linked Life Data

11003155

Source:http://linkedlifedata.com/resource/pubmed/id/11003155

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2000-12-27
pubmed:abstractText
The synthesis of a series of novel 2-aryl substituted 4H-3,1-benzoxazin-4-ones and their evaluation as specific inhibitors of the Tissue Factor (TF)/Factor VIIa (FVIIa)-induced pathway of coagulation is reported. Inhibitory activities (IC50 values) in the range 0.17 to > 40 microM on the activation of Factor X (FX) by the TF/FVIIa complex were found for compounds having one or two electronegative substituents such as F, Cl and NO2 in the 2-aryl substituent. Different substitutions both electron-attracting and donating groups were allowed in the 5, 6, 7 and 8 positions. Several of the compounds showed a selectivity ratio towards FX and thrombin of > 50, thus being the first small molecules described as potential drugs for oral antithrombotic treatment without side effects such as bleeding which is observed especially with thrombin inhibitors. The best substituent pattern being the 2-aryl group substituted with: 2-F; 2,6-F2; or 2-FX; 6-Cl; together with electronegative substitution in the 5, 6, 7, or 8 positions. 2-Heteroaryl substituents like thienyl and furanyl were of low activity while some 2-(2-chloro-3-pyridyl) derivatives had inhibitory activity < 10 microM and a good selectivity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2095-103
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Inhibitors of the tissue factor/factor VIIa-induced coagulation: synthesis and in vitro evaluation of novel specific 2-aryl substituted 4H-3,1-benzoxazin-4-ones.
pubmed:affiliation
Medicinal Chemistry Research, Novo Nordisk A/S, Maaloev, Denmark.
pubmed:publicationType
Journal Article