Linked Life Data

18729445

Source:http://linkedlifedata.com/resource/pubmed/id/18729445

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2008-9-19
pubmed:abstractText
3,4-Dihydro-2 H-1,4-benzoxazine derivatives possessing both thrombin inhibitory and glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonistic activities were obtained by combining mimetics of the d-Phe-Pro-Arg pharmacophore of thrombin inhibitors and the Arg-Gly-Asp pharmacophore of GPIIb/IIIa receptor antagonists in the same low molecular weight peptidomimetic compound. Systematic variation of the position of substituents around the 3,4-dihydro- 2H-1,4-benzoxazine nucleus, the distance between the carboxylate and amidine moieties, together with additional substituents to fill the thrombin S 2 and S 3 pockets resulted in compounds displaying submicromolar inhibition constants ( K i) for thrombin and submicromolar IC 50 for inhibition of binding of fibrinogen to platelet GPIIb/IIIa receptor. Some of these compounds, such as 17a, 17b, 17d, and 17h possessing a well balanced activity at both targets, are a good starting point for further optimization. Incorporation of anticoagulant and platelet antiaggregatory activity in the same molecule constitutes a promising approach toward novel antithrombotic agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5617-29
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
3,4-Dihydro-2H-1,4-benzoxazine derivatives combining thrombin inhibitory and glycoprotein IIb/IIIa receptor antagonistic activity as a novel class of antithrombotic compounds with dual function.
pubmed:affiliation
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, SI-1000 Ljubljana, Slovenia.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't