54911-89-6Relevant articles and documents
METHODS AND COMPOSITIONS FOR TREATING AND/OR PREVENTING MUCOSITIS
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, (2015/04/15)
Methods for treating and/or preventing mucositis comprising administering to a subject in need thereof an effective amount of at least one compound chosen from E-selectin antagonists, pharmaceutically acceptable salts of E-selectin antagonists, prodrugs of E- selectin antagonists, and pharmaceutically acceptable salts of prodrugs of E-selectin antagonists, and compositions comprising at least one of such compound.
E-SELECTIN ANTAGONIST COMPOUNDS AND METHODS OF USE
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Page/Page column 68; 69, (2014/05/24)
Provided herein are E-selectin antagonist therapeutic agents and improvements thereto and compositions comprising these E-selectin antagonists. Methods are also provided for using these E-selectin antagonist therapeutic agents to treat and/or prevent diseases and disorders treatable by inhibiting binding of an E-selectin to an E-selectin ligand. Also provided herein improvements to E-selectin antagonist giycomimetic compounds that improve the oral bioavailability of the giycomimetic compounds.
Pre-organization of the core structure of E-selectin antagonists
Schwizer, Daniel,Patton, John T.,Cutting, Brian,Smiesko, Martin,Wagner, Beatrice,Kato, Ako,Weckerle, Celine,Binder, Florian P. C.,Rabbani, Said,Schwardt, Oliver,Magnani, John L.,Ernst, Beat
supporting information; experimental part, p. 1342 - 1351 (2012/04/04)
A new class of N-acetyl-dglucosamine (GlcNAc) mimics for Eselectin antagonists was designed and synthesized. The mimic consists of a cyclohexane ring substituted with alkyl substituents adjacent to the linking position of the fucose moiety. Incorporation into E-selectin antagonists led to the test compounds 8 and the 2'-benzoylated analogues 21, which exhibit affinities in the low micromolar range. By using saturation transfer difference (STD)-NMR it could be shown that the increase in affinity does not result from an additional hydrophobic contact of the alkyl substituent with the target protein E-selectin, but rather from a steric effect stabilizing the antagonist in its bioactive conformation. The loss of affinity found for antagonists 10 and 35 containing a methyl substituent in a remote position (and therefore unable to support to the stabilization of the core) further supports this hypothesis. Finally, when a GlcNAc mimetic containing two methyl substituents (52 and 53) was used, in which one methyl was positioned adjacent to the fucose linking position and the other was in a remote position, the affinity was regained.
