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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
25
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pubmed:dateCreated |
2001-11-30
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pubmed:abstractText |
We have shown that p-arylthio cinnamides can inhibit the interaction of LFA-1 and ICAM-1, which is involved in cell adhesion and the inflammatory process. We now show that 2,3-disubstitution on the aryl portion of the cinnamide results in enhanced activity over mono substitution on the ring. The best 2,3-substituents were chlorine and trifluoromethyl groups. Compounds 39 and 40 which contain two CF3 groups have IC(50) values of 0.5 and 0.1 nM, respectively, in inhibiting JY8 cells expressing LFA-1 on their surface, from adhering to ICAM-1. The structure-activity relationship (SAR) was examined using an NMR based model of the LFA-1 I domain/compound 31 complex. One of our compounds (38) was able to reduce cell migration in two different in vivo experiments.
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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 |
Dec
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:DeVriesPP,
pubmed-author:DickinsonRR,
pubmed-author:FreemanJJ,
pubmed-author:HuthJ RJR,
pubmed-author:KesterJJ,
pubmed-author:LeitzaSS,
pubmed-author:LinNN,
pubmed-author:LiuJ CJC,
pubmed-author:LynchJJ,
pubmed-author:MussattoDD,
pubmed-author:OkasinskiG FGF,
pubmed-author:PerSS,
pubmed-author:ReillyE BEB,
pubmed-author:WinnMM,
pubmed-author:XieSS,
pubmed-author:von GeldernT WTW
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4393-403
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:11728185-Amides,
pubmed-meshheading:11728185-Animals,
pubmed-meshheading:11728185-Cell Line,
pubmed-meshheading:11728185-Chemotaxis, Leukocyte,
pubmed-meshheading:11728185-Cinnamates,
pubmed-meshheading:11728185-Enterotoxins,
pubmed-meshheading:11728185-Eosinophils,
pubmed-meshheading:11728185-Indoles,
pubmed-meshheading:11728185-Intercellular Adhesion Molecule-1,
pubmed-meshheading:11728185-Lymphocyte Function-Associated Antigen-1,
pubmed-meshheading:11728185-Magnetic Resonance Spectroscopy,
pubmed-meshheading:11728185-Mice,
pubmed-meshheading:11728185-Models, Molecular,
pubmed-meshheading:11728185-Neutrophils,
pubmed-meshheading:11728185-Ovalbumin,
pubmed-meshheading:11728185-Pneumonia,
pubmed-meshheading:11728185-Rats,
pubmed-meshheading:11728185-Staphylococcus aureus,
pubmed-meshheading:11728185-Structure-Activity Relationship,
pubmed-meshheading:11728185-Sulfides
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pubmed:year |
2001
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pubmed:articleTitle |
Discovery of novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 4. Structure-activity relationship of substituents on the benzene ring of the cinnamide.
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pubmed:affiliation |
Metabolic Disease Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064-6098, USA. marty.winn@abbott.com
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pubmed:publicationType |
Journal Article
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