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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 |
2008-1-14
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pubmed:abstractText |
A novel class of potent CCR3 receptor antagonists were designed and synthesized starting from N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide (1),which was found by subjecting our chemical library to high throughput screening (HTS). The CCR3 inhibitory activity of the synthesized compounds against eotaxin-induced Ca(2+) influx was evaluated using CCR3-expressing preB cells. Systematic chemical modifications of 1 revealed that the 6-fluoro-2-naphthylmethyl moiety was essential for CCR3 inhibitory activity in this new series of CCR3 antagonists. Further structural modifications of the benzamide and piperidine moieties of 1 led to the identification of exo-N-{8-[(6-fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3- yl}biphenyl-2-carboxamide [corrected] (31) as a potent CCR3 antagonist with an IC(50) value of 0.020 microM.
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pubmed:commentsCorrections |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1464-3391
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pubmed:author |
pubmed-author:HamadaNoritakaN,
pubmed-author:ImaokaTakayukiT,
pubmed-author:InamiHiroshiH,
pubmed-author:IuraYosukeY,
pubmed-author:KubotaHirokazuH,
pubmed-author:MorihiraKoichiroK,
pubmed-author:MorokataTatsuakiT,
pubmed-author:NittaAikoA,
pubmed-author:OhtaMitsuakiM,
pubmed-author:SatoIppeiI,
pubmed-author:SuzukiKeikoK,
pubmed-author:TakahashiToshiyaT,
pubmed-author:TakeuchiMakotoM,
pubmed-author:TsukamotoShin-ichiS
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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 |
144-56
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pubmed:dateRevised |
2008-9-11
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pubmed:meshHeading |
pubmed-meshheading:17951061-Benzamides,
pubmed-meshheading:17951061-Calcium,
pubmed-meshheading:17951061-Chemokine CCL11,
pubmed-meshheading:17951061-Humans,
pubmed-meshheading:17951061-Inhibitory Concentration 50,
pubmed-meshheading:17951061-Precursor Cells, B-Lymphoid,
pubmed-meshheading:17951061-Receptors, CCR3,
pubmed-meshheading:17951061-Small Molecule Libraries,
pubmed-meshheading:17951061-Structure-Activity Relationship
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pubmed:year |
2008
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pubmed:articleTitle |
Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide derivatives as novel CCR3 antagonists.
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pubmed:affiliation |
Drug Discovery Research, Astellas Pharma Inc., 21Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. ippei.sato@jp.astellas.com
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pubmed:publicationType |
Journal Article
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