928847-07-8Relevant academic research and scientific papers
Rational design of novel, potent small molecule pan-selectin antagonists
Kranich, Remo,Busemann, Anke S.,Bock, Daniel,Schroeter-Maas, Sabine,Beyer, Diana,Heinemann, Bo,Meyer, Michael,Schierhorn, Katrin,Zahlten, Rainer,Wolff, Gerhard,Aydt, Ewald M.
, p. 1101 - 1115 (2007/10/03)
This report describes the first results of a rational hit-finding strategy to design novel small molecule antiinflammatory drugs targeting selectins, a family of three cellular adhesion molecules. Based on recent progress in understanding of molecular interaction between selectins and their natural ligands as well as progress in clinical development of synthetic antagonists like 1 (bimosiamose, TBC1269), this study was initiated to discover small molecule selectin antagonists with improved pharmacological properties. Considering 1 as template structure, a ligand-based approach followed by focused chemical synthesis has been applied to yield novel synthetic small molecules (MWr 500) with a trihydroxybenzene motif, bearing neither peptidic nor glycosidic components, with nanomolar in vitro activity. Biological evaluation involves two kinds of in vitro assays, a static molecular binding assay, and a dynamic HL-60 cell attachment assay. As compared to controls, the novel compounds showed improved biological in vitro activity both under static and dynamic conditions.
Novel aromatic compounds and their use in medical applications
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Page/Page column 26, (2010/11/26)
Pharmaceutical compositions comprising at least one compound of the formulas (Ia) or (Ib) and a pharmaceutically acceptable carrier which is useful in a medicine wherein the symbols and substituents have the following meaning -X- is e.g. or or or and Y being or or the pharmaceutically acceptable salts, esters or amides and prodrugs of the above identified compounds of formulas (Ia) or (Ib). The compounds are applied to modulate the in-vitro and in-vivo binding processes mediated by E-, P- or L-selectin binding.
