Source:http://linkedlifedata.com/resource/pubmed/id/17988878
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2008-3-3
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pubmed:abstractText |
Previously, ethyl 4-(1-benzyl-1H-indazol-3-yl)benzoate (YD-3) was identified by us as the first non-peptide protease-activated receptor 4 (PAR4) antagonist. To continue on our development of novel anti-PAR4 agents, YD-3 was used as a lead compound and a series of its derivatives were synthesized and evaluated for their selective anti-PAR4 activity. Through structure-activity relationship (SAR) study, we identified the important functional groups contributing to anti-PAR4 activity, and these functional groups were kept intact during subsequent structural modification. Several new compounds with anti-PAR4 activity comparable to YD-3 were identified. Among them, ethyl 4-[1-(3-chlorobenzyl)-1H-indazol-3-yl]benzoate (33) showed the most potent inhibitory effect on PAR4-mediated platelet aggregation, ATP release, and P-selectin expression. On the other hand, ethyl 4-(1-phenyl-1H-indazol-3-yl)benzoate (83) exhibited dual inhibitory effects on PAR4 and thromboxane formation from arachidonic acid. The above findings can be used as guidelines for development of novel antiplatelet drug candidates.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1464-3391
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1262-78
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pubmed:meshHeading |
pubmed-meshheading:17988878-Adenosine Triphosphate,
pubmed-meshheading:17988878-Benzoates,
pubmed-meshheading:17988878-Blood Platelets,
pubmed-meshheading:17988878-Humans,
pubmed-meshheading:17988878-Molecular Structure,
pubmed-meshheading:17988878-P-Selectin,
pubmed-meshheading:17988878-Platelet Aggregation Inhibitors,
pubmed-meshheading:17988878-Structure-Activity Relationship
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pubmed:year |
2008
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pubmed:articleTitle |
Synthesis and antiplatelet activity of ethyl 4-(1-benzyl-1H-indazol-3-yl)benzoate (YD-3) derivatives.
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pubmed:affiliation |
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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