Drug design, synthesis, and evaluation of a non-sugar-based selectin antagonist.
We have designed a series of simple rigid compounds (2) having a phenyl ring attached to three essential groups necessary for selectin binding, i.e., a fucose unit, a carboxylic acid, and the hydrophobic part. In this series of compound 2, 2a exhibited strong inhibitory activity in in vitro P-selectin mediated cell adhesion assay. The novel type of compound 2a would be a potential lead compound for selectin antagonist.
Fukunaga
K
K
Department of Chemistry, R&D Labs, Nippon Organon K.K., Tomobuchi-cho, Miyakojima-ku, Osaka 534-0016, Japan.
Tsukida
T
T
Moriyama
H
H
Kondo
H
H
D001565:Benzoates / Q000737:chemistry* / Q000494:pharmacology*; D001671:Biochemistry / Q000379:methods; D002241:Carbohydrates / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005643:Fucose / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D018716:Molecular Mimicry; D015394:Molecular Structure; D019007:P-Selectin / Q000187:drug effects*; D013329:Structure-Activity Relationship; D018675:Toxicity Tests
C442392:3-carboxy-5-(2-tetradecylhexadecylaminocarbonyl)phenylthio fucopyranoside; D001565:Benzoates; D002241:Carbohydrates; D019007:P-Selectin; D005643:Fucose