Lisofylline

Lisofylline

Skeletal formula of lisofylline
Space-filling model of the lisofylline molecule
Systematic (IUPAC) name
1-[(5R)-5-Hydroxyhexyl]-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione
Identifiers
CAS Number	100324-81-0 N
PubChem	CID: 501254
ChemSpider	438549 Y
UNII	L1F2Q2X956 Y
ChEMBL	CHEMBL1411 Y
Synonyms	1-(5-Hydroxyhexyl)-3,7-dimethylxanthine (HDX)
Chemical data
Formula	C13H20N4O3
Molecular mass	280.32 g/mol
SMILES O=C2N(c1ncn(c1C(=O)N2CCCC[C@H](O)C)C)C
InChI InChI=1S/C13H20N4O3/c1-9(18)6-4-5-7-17-12(19)10-11(14-8-15(10)2)16(3)13(17)20/h8-9,18H,4-7H2,1-3H3/t9-/m1/s1 Y Key:NSMXQKNUPPXBRG-SECBINFHSA-N Y
NY (what is this?)  (verify)

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 5,567,704 NB

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:

External links

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