Lisofylline

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Lisofylline
Skeletal formula of lisofylline
Space-filling model of the lisofylline molecule
Clinical data
Other names1-(5-Hydroxyhexyl)-3,7-dimethylxanthine (HDX)
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC13H20N4O3
Molar mass280.328 g·mol−1
3D model (JSmol)
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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[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.

DE 3942872 ; eidem, U.S. Patent 5,310,666 (1991, 1994 both to Hoechst). Asymmetric synthesis: J. P. Klein et al., WO 9531450  (1995 to Cell Therapeutics).

For analogs see:[8]

References[edit]

  1. ^ 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.
  2. ^ 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.
  3. ^ 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.
  4. ^ Matteson DS, Jesthi PK, Sadhu KM (1984). "Synthesis and properties of pinanediol .alpha.-amido boronic esters". Organometallics. 3 (8): 1284. doi:10.1021/om00086a024.
  5. ^ Matteson DS (1988). "Asymmetric synthesis with boronic esters". Accounts of Chemical Research. 21 (8): 294–300. doi:10.1021/ar00152a002.
  6. ^ Matteson DS (October 2013). "Boronic esters in asymmetric synthesis". The Journal of Organic Chemistry. 78 (20): 10009–23. doi:10.1021/jo4013942. PMID 23875690.
  7. ^ 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. 17 (47): 13124–32. doi:10.1002/chem.201102581. PMID 22052475.
  8. ^ 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.

External links[edit]