Lisofylline

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Lisofylline (LSF) is a synthetic small molecule with novel anti-inflammatory properties. LSF can effectively prevent type 1 diabetes in preclinical models and improves the function and viability of isolated or transplanted pancreatic islets. It is a metabolite of pentoxifylline.

As well, LSF improves cellular mitochondrial function and blocks interleukin-12 (IL-12) signaling and STAT-4 activation in target cells and tissues. IL-12 and STAT-4 activation are important pathways linked to inflammation and autoimmune damage to insulin producing cells. Therefore, LSF and related analogs could provide a new therapeutic approach to prevent or reverse type 1 diabetes. LSF also directly reduces glucose-induced changes in human kidney cells suggesting that LSF and analogs have the potential to treat the complications associated with diabetes.

Synthesis

The R enantiomer of the pentoxyfylline analogue in which the ketone has been reduced to an alcohol shows enhanced activity as an inhibitor of acetyl CoA over the parent drug.

File:Lisofylline synthesis.svg

Lisofylline synthesis: U.S. patent 5567704 NB

For analogs see:

Further reading

• Template:Citation/make link, Aretz, Werner; Furrer, Harald & Gebert, Ulrich et al., "Verfahren zur enantioselektiven Darstellung von (ω-1)-Hydroxyalkylxanthinen [Method for the enantioselective preparation of(ω-1)-hydroxyalkylxanthines]", published , assigned to Hoechst AG 
• Template:Citation/make link, Aretz, Werner; Furrer, Harald & Gebert, Ulrich et al., "Process for the enantioselective preparation of (β-1)-hydroxyalkylxanthines by reduction using Rhodotorula rubra", published , assigned to Hoechst AG 
• Template:Citation/make link, Klein, J. Peter; Leigh, Alistair J. & Michnick, John et al., "Asymmetric synthesis of chiral secondary alcohols", published , assigned to Cell Therapeutics Inc. 

External links

• University of Virginia Research Announcement
• National Institute of Health on Lisofylline
• Metabolism of lisofylline in the human liver