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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-1-4
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pubmed:abstractText |
P-selectin-PSGL-1 interaction causes rolling of leukocytes on the endothelial cell surface, which subsequently leads to firm adherence and leukocyte transmigration through the vessel wall into the surrounding tissues. P-selectin is upregulated on the surface of both platelets and endothelium in a variety of atherosclerosis-associated conditions. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of atherosclerosis. High-throughput screening and subsequent analoging had led to the identification of compound 1 as the lead candidate. Herein, we report the continuation of this work and the discovery of a second-generation series, the tetrahydrobenzoquinoline salicylic acids. These compounds have improved pharmacokinetic properties, and a number of them have shown oral efficacy in mouse and rat models of atherogenesis and vascular injury. The lead 31 (PSI-697), is currently in clinical development for the treatment of atherothrombotic vascular events.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-chlorobenzyl)-3-hydroxy-7,8,9,1...,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins E,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrinolytic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/P-Selectin,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Salicylic Acids
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BedardPatricia WPW,
pubmed-author:CamphausenRaymond TRT,
pubmed-author:ClerinValerieV,
pubmed-author:DeBernardoSilvanoS,
pubmed-author:HuangAdrianA,
pubmed-author:JanzKristinK,
pubmed-author:KailaNeeluN,
pubmed-author:KeithJames CJCJr,
pubmed-author:MorettoAlessandroA,
pubmed-author:SchaubRobert GRG,
pubmed-author:ShawGray DGD,
pubmed-author:StentV CVC,
pubmed-author:SushkovaNataliaN,
pubmed-author:TsaoDesirée H HDH,
pubmed-author:WangQinQ
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
40-64
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pubmed:meshHeading |
pubmed-meshheading:17201409-Administration, Oral,
pubmed-meshheading:17201409-Animals,
pubmed-meshheading:17201409-Apolipoproteins E,
pubmed-meshheading:17201409-Atherosclerosis,
pubmed-meshheading:17201409-Carotid Stenosis,
pubmed-meshheading:17201409-Dogs,
pubmed-meshheading:17201409-Fibrinolytic Agents,
pubmed-meshheading:17201409-Hydroxyquinolines,
pubmed-meshheading:17201409-Indoles,
pubmed-meshheading:17201409-Leukocyte Rolling,
pubmed-meshheading:17201409-Male,
pubmed-meshheading:17201409-Mice,
pubmed-meshheading:17201409-Mice, Knockout,
pubmed-meshheading:17201409-P-Selectin,
pubmed-meshheading:17201409-Quinolines,
pubmed-meshheading:17201409-Rats,
pubmed-meshheading:17201409-Rats, Sprague-Dawley,
pubmed-meshheading:17201409-Salicylic Acids,
pubmed-meshheading:17201409-Structure-Activity Relationship
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pubmed:year |
2007
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pubmed:articleTitle |
2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H]quinoline-4-carboxylic acid (PSI-697): identification of a clinical candidate from the quinoline salicylic acid series of P-selectin antagonists.
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pubmed:affiliation |
Chemical and Screening Sciences, Cardiovascular and Metabolic Disease, Drug Safety and Metabolism, Wyeth Research, Cambridge, Massachusetts 02140, USA. nkaila@wyeth.com
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pubmed:publicationType |
Journal Article
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