640291-24-3Relevant academic research and scientific papers
The 'Ethereal' nature of TLR4 agonism and antagonism in the AGP class of lipid A mimetics
Bazin, Helene G.,Murray, Tim J.,Bowen, William S.,Mozaffarian, Afsaneh,Fling, Steven P.,Bess, Laura S.,Livesay, Mark T.,Arnold, Jeffrey S.,Johnson, Craig L.,Ryter, Kendal T.,Cluff, Christopher W.,Evans, Jay T.,Johnson, David A.
scheme or table, p. 5350 - 5354 (2009/08/07)
To overcome the chemical and metabolic instability of the secondary fatty acyl residues in the AGP class of lipid A mimetics, the secondary ether lipid analogs of the potent TLR4 agonist CRX-527 (2) and TLR4 antagonist CRX-526 (3) were synthesized and evaluated along with their ester counterparts for agonist/antagonist activity in both in vitro and in vivo models. Like CRX-527, the secondary ether lipid 4 showed potent agonist activity in both murine and human models. Ether lipid 5, on the other hand, showed potent TLR4 antagonist activity similar to CRX-526 in human cell assays, but did not display any antagonist activity in murine models and, in fact, was weakly agonistic. Glycolipids 2, 4, and 5 were synthesized via a new highly convergent method utilizing a common advanced intermediate strategy. A new method for preparing (R)-3-alkyloxytetradecanoic acids, a key component of ether lipids 4 and 5, is also described.
