Lisofylline
![]() | |
![]() | |
Clinical data | |
---|---|
Other names | 1-(5-Hydroxyhexyl)-3,7-dimethylxanthine (HDX) |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
Chemical and physical data | |
Formula | C13H20N4O3 |
Molar mass | 280.328 g·mol−1 |
3D model (JSmol) | |
| |
| |
![]() ![]() |
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
[edit]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.
![](https://upload.wikimedia.org/wikipedia/commons/thumb/6/63/Lisofylline_synthesis.svg/700px-Lisofylline_synthesis.svg.png)
For analogs see:[8]
Further reading
[edit]- DE 3942872, 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 1991-06-27, assigned to Hoechst AG - US 5310666, Aretz, Werner; Furrer, Harald & Gebert, Ulrich et al., "Process for the enantioselective preparation of (
β -1)-hydroxyalkylxanthines by reduction using Rhodotorula rubra", published 1994-05-10, assigned to Hoechst AG - WO 9531450, Klein, J. Peter; Leigh, Alistair J. & Michnick, John et al., "Asymmetric synthesis of chiral secondary alcohols", published 1995-11-23, assigned to Cell Therapeutics Inc.
References
[edit]- ^ Matteson DS, Sadhu KM, Peterson ML (1986). "99% Chirally selective synthesis via pinanediol boronic esters: Insect pheromones, diols, and an amino alcohol". Journal of the American Chemical Society. 108 (4): 810. doi:10.1021/ja00264a039.
- ^ Matteson DS, Ray R, Rocks RR, Tsai DJ (1980). "Directed chiral synthesis with pinanediol boronic esters". Journal of the American Chemical Society. 102 (25): 7590. doi:10.1021/ja00545a046.
- ^ Matteson DS, Jesthi PK, Sadhu KM (1997). "Asymmetric synthesis of alkylarylcarbinols via reaction of a chiral pinanediol alkylboronic ester with arylmethyl chlorides". Tetrahedron: Asymmetry. 8 (23): 3843. doi:10.1016/S0957-4166(97)00565-X.
- ^ Matteson DS, Jesthi PK, Sadhu KM (1984). "Synthesis and properties of pinanediol .alpha.-amido boronic esters". Organometallics. 3 (8): 1284. doi:10.1021/om00086a024.
- ^ Matteson DS (1988). "Asymmetric synthesis with boronic esters". Accounts of Chemical Research. 21 (8): 294–300. doi:10.1021/ar00152a002.
- ^ Matteson DS (October 2013). "Boronic esters in asymmetric synthesis". The Journal of Organic Chemistry. 78 (20): 10009–23. doi:10.1021/jo4013942. PMID 23875690.
- ^ Scott HK, Aggarwal VK (November 2011). "Highly enantioselective synthesis of tertiary boronic esters and their stereospecific conversion to other functional groups and quaternary stereocentres". Chemistry: A European Journal. 17 (47): 13124–32. doi:10.1002/chem.201102581. PMID 22052475.
- ^ Cui P, Macdonald TL, Chen M, Nadler JL (July 2006). "Synthesis and biological evaluation of lisofylline (LSF) analogs as a potential treatment for Type 1 diabetes". Bioorganic & Medicinal Chemistry Letters. 16 (13): 3401–5. doi:10.1016/j.bmcl.2006.04.036. PMID 16650991.