β-C-Mannosides as Selectin Inhibitors

• Published in: Journal of medicinal chemistry Vol. 45; no. 8; pp. 1563 - 1566
• Main Authors: Kaila, Neelu, Chen, Lihren, Thomas, Tsao, Desiree, Tam, Steve, Bedard, Patricia W, Camphausen, Raymond T, Alvarez, Juan C, Ullas, Giliyar
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 11.04.2002; Amer Chemical Soc
• Subjects: Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Chemistry, Medicinal; Combinatorial Chemistry Techniques; Crystallography, X-Ray; E-Selectin - chemistry; Enzyme-Linked Immunosorbent Assay; Humans; Life Sciences & Biomedicine; Ligands; Magnetic Resonance Spectroscopy; Mannosides - chemical synthesis; Mannosides - chemistry; Medical sciences; Membrane Glycoproteins - chemistry; Models, Molecular; Oligosaccharides - chemistry; P-Selectin - chemistry; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Protein Binding; Science & Technology; Structure-Activity Relationship; LIGANDS; SLE(X); CARBOHYDRATE INTERACTIONS; Carbohydrate antigen; Sialic acid; E Selectin; Cell adhesion molecule; Combinatorial chemistry; Liquid phase; Adhesion; Lewis system; P Selectin; Screening; α-Aminoacid; Structure activity relation; Chemical compound library; D-manno stereoisomer; Carboxamide; Inhibitor; C-Glycoside; Chemical synthesis; ELISA assay
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm010390f

Potential E- and P-selectin inhibitors were synthesized to explore a hydrophobic area on the E-selectin surface and the PSGL-1 protein binding site on the P-selectin surface that was recently defined by crystallography. Three series of mannose-based compounds (libraries A, B, and C) were synthesized using solution phase parallel synthesis. Biological evaluation of these compounds was done using two ELISA-based assays and transferred NOE (trNOE) experiments. Some of the compounds showed better activity than sLex in the P-selectin assay.