Synthesis and biological evaluation of a sialyl Lewis X mimic with significantly improved E-selectin inhibition |
| |
Authors: | Thoma G Magnani J L Patton J T |
| |
Institution: | Novartis Pharma AG, Basel, Switzerland. gebhard.thoma@pharma.novartis.com |
| |
Abstract: | The synthesis of the highly potent E-selectin inhibitor 5 is described. Sialyl Lewis X mimic 5 was rationally designed by combining two previously disclosed beneficial sLe(x) modifications in a single molecule. The compound was found to be 30-fold more potent than sLe(x) in a static, cell-free equilibrium assay. Furthermore, compound 5 was highly active (IC50 = 10 microM) in a dynamic non-equilibrium assay in which sLe(x) did not inhibit neutrophil rolling at up to 1000 microM. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |