100324-80-9

Basic information

• Product Name: (S)-Lisofylline
• Synonyms: (S)-Lisofylline;1-[(5S)-5-hydroxyhexyl]-3,7-dimethylpurine-2,6-dione
• CAS NO: 100324-80-9
• Molecular Formula: C₁₃H₂₀N₄O₃
• Molecular Weight: 280.3229
• Mol File: 100324-80-9.mol
• Article Data: 17

Chemical Properties

• Appearance: /
• Solubility: ≤15mg/ml in ethanol;3mg/ml in DMSO;12mg/ml in dimethyl formamide
• CAS DataBase Reference: (S)-Lisofylline(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-Lisofylline(100324-80-9)
• EPA Substance Registry System: (S)-Lisofylline(100324-80-9)

Safety Data

• Hazardous Substances Data: 100324-80-9(Hazardous Substances Data)

Usage

Description

(S)-Lisofylline, also known as (S)-LSF, is a chiral metabolite of pentoxifylline that acts as a potent anti-inflammatory agent. It is the pharmacologically inactive optical enantiomer of (R)-LSF, the biologically active isomer. When metabolized by isolated human liver cells, pentoxifylline is predominantly reduced to (S)-Lisofylline in the cytosol, and liver microsomes show 85% stereoselectivity in favor of (S)-Lisofylline formation. This makes pentoxifylline an inefficient prodrug for the delivery of therapeutically relevant lisofylline.

Uses

Used in Pharmaceutical Industry:
(S)-Lisofylline is used as an anti-inflammatory agent for its potent anti-inflammatory properties. It is particularly useful in the development of drugs targeting inflammation-related conditions and diseases.
Used in Drug Metabolism Research:
(S)-Lisofylline is used as a subject of study in understanding the metabolism of pentoxifylline and the stereoselectivity of liver cells in metabolizing this compound. This knowledge can be applied to improve the efficiency of prodrugs and their delivery of therapeutically relevant agents.
Used in Drug Development:
(S)-Lisofylline is used as a starting point for the development of more efficient prodrugs and drug delivery systems. By understanding the metabolism and stereoselectivity of (S)-Lisofylline, researchers can design better prodrugs that effectively deliver the therapeutically relevant (R)-Lisofylline to target tissues and cells.

in vivo

in rats subjected to hemorrhagic shock and resuscitation, lsf increased the intestinal and hepatic blood flow. treatment with lsf (15 mg/kg) ameliorated the development of mucosal damage and hyperpermeability. rats treated with lsf showed lower plasma concentrations of the intracellular hepatic enzyme, aspartate aminotransferase. lsf treatment increased concentrations of adenosine triphosphate in intestinal and hepatic tissue [1]. in nod mice, lisofylline suppressed ifn-γ production, reduced the onset of insulitis and diabetes, and inhibited diabetes after transfer of splenocytes from lisofylline-treated donors to nod.scid recipients [3].

references

[1] wattanasirichaigoon s, menconi m j, fink m p. lisofylline ameliorates intestinal and hepatic injury induced by hemorrhage and resuscitation in rats[j]. critical care medicine, 2000, 28(5): 1540-1549.[2] lillibridge, j. a.,kalhorn, t.f. and slattery, j.t. metabolism of lisofylline and pentoxifylline in human liver microsomes and cytosol. drug metabolism and disposition 24(11), 1174-1179 (1996).[3] yang z d, chen m, wu r, et al. the anti-inflammatory compound lisofylline prevents type i diabetes in non-obese diabetic mice[j]. diabetologia, 2002, 45(9): 1307-1314.[4] chen m, yang z, wu r, et al. lisofylline, a novel antiinflammatory agent, protects pancreatic β-cells from proinflammatory cytokine damage by promoting mitochondrial metabolism[j]. endocrinology, 2002, 143(6): 2341-2348.

Upstream product

• 154719-57-0 1-(5,6-oxidohexyl)-3,7-dimethylxanthine 
• 6493-05-6 pentoxyphylline 
• 624-45-3 levulinic acid methyl ester 
• 6493-06-7 1-(5-hydroxyhexyl)theobromine 
• 693-38-9 vinyl palmitate 
• 4704-31-8 vinyl caprate 
• 123-20-6 vinyl n-butyrate 
• 108-05-4 vinyl acetate 
• 83-67-0 theobromine / 
• 10226-30-9 6-chloro-2-hexanone 
• 67-63-0 isopropyl alcohol 
• 67-56-1 methanol 

Downstream Products

• 100324-81-0 lisofylline 
• 174455-55-1 6-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)hexan-2-yl acetate 
• 174455-55-1 6-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)hexan-2-yl acetate 
• 174455-55-1 6-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)hexan-2-yl acetate 
• 117835-33-3 3-Methyl-5-methylamino-3H-imidazole-4-carboxylic acid (5-methoxy-hexyl)-amide; compound with picric acid 

Relevant articles and documents

The effect of pentoxifylline and its metabolite-1 on inflammation and fibrosis in the TNBS model of colitis

TNBS-induced colitis has characteristics resembling human Crohn's disease including transmural inflammation, ulceration, and fibrosis. Current treatments target acute symptoms but do not necessarily prevent fibrotic complications of the disease. The aim of this study was to determine the effect of pentoxifylline and its primary metabolite (M-1) on fibrosis in the TNBS-induced colitis model. Myeloperoxidase activity and interleukin-18 are indicators of inflammation and were elevated in the TNBS model. The morphology damage score assesses colon damage and was also elevated in the TNBS model. Collagen as the indicator of fibrosis was quantified and visualized by the Sirius Red/Fast Green staining technique and collagen type I was assessed by Western analysis. Collagen was elevated in the TNBS-induced model. Pentoxifylline and M-1 treatment significantly attenuated colon damage and inflammation in TNBS-colitis (P 0.05). M-1 treatment significantly reduced the TNBS-induced increase in colon weight, colon thickness and total collagen content (P 0.05). Results suggest that pentoxifylline and M-1 inhibit intestinal fibrosis in this experimental model and may prove beneficial in the treatment of intestinal fibrosis associated with human Crohn's disease with the added benefit of inhibiting inflammation and ulceration. This is the first study to examine the effects of racemic M-1 in vivo and one of the few studies to examine the effect of drugs on both inflammation and fibrosis in an experimental model of colitis.

PK/PD studies on non-selective PDE inhibitors in rats using cAMP as a marker of pharmacological response

In recent years, phosphodiesterase (PDE) inhibitors have been frequently tested for the treatment of experimental inflammatory and immune disorders. It is suggested that anti-inflammatory properties of PDE inhibitors are related to their ability to increase cAMP levels. The aim of this study was to verify the hypothesis that cAMP may be a useful marker of pharmacological response following administration of non-selective PDE inhibitors (pentoxifylline and (±)-lisofylline) to endotoxemic rats. Male Wistar rats were administered LPS (1?mg?kg?1, i.v.) simultaneously with either compound given at two doses (40 and 80?mg?kg?1, i.v.). Levels of cAMP and both compounds in animal plasma were measured by the validated HPLC methods. Pharmacokinetic-pharmacodynamic analysis was performed using basic and modified indirect response (IDR) models II in Phoenix WinNonlin. The results of this study indicate that, in contrast to pentoxifylline, (±)-lisofylline demonstrates a non-linear pharmacokinetics in rats with endotoxemia. In vitro study using human recombinant PDE4B and PDE7A revealed the occurrence of additive interaction between studied compounds. Moreover, (±)-lisofylline is a more potent inhibitor of PDEs compared to pentoxifylline, as evidenced by lower IC50 values. Following administration of both compounds, levels of cAMP in rat plasma increased in a dose-dependent manner. The modified IDR model II better described cAMP levels over time profiles. The validity of the proposed marker was confirmed by measuring plasma TNF-α levels in the studied animals. In conclusion, cAMP may be used in future preclinical and clinical studies of some PDE inhibitors to evaluate the drug concentration–effect relationship.

Efficient Transfer Hydrogenation of Ketones using Methanol as Liquid Organic Hydrogen Carrier

Herein, we demonstrate an efficient protocol for transfer hydrogenation of ketones using methanol as practical and useful liquid organic hydrogen carrier (LOHC) under Ir(III) catalysis. Various ketones, including electron-rich/electron-poor aromatic ketones, heteroaromatic and aliphatic ketones, have been efficiently reduced into their corresponding alcohols. Chemoselective reduction of ketones was established in the presence of various other reducible functional groups under mild conditions.

Role of Chain Length and Degree of Unsaturation of Fatty Acids in the Physicochemical and Pharmacological Behavior of Drug-Fatty Acid Conjugates in Diabetes

Several drug-fatty acid (FA) prodrugs have been reported to exhibit desirable physicochemical and pharmacological profile; however, comparative beneficial effects rendered by different FAs have not been explored. In the present study, four different FAs (linoleic acid, oleic acid, palmitic acid, and α-lipoic acid) were selected based on their chain length and degree of unsaturation and conjugated to Lisofylline (LSF), an antidiabetic molecule to obtain different drug-FA prodrugs and characterized for molecular weight, hydrophobicity, purity, self-assembly, and efficacy in vitro and in vivo in type 1 diabetes model. Prodrugs demonstrated a 2- to 6-fold increase in the plasma half-life of LSF. Diabetic animals treated with prodrugs, once daily for 5 weeks, maintained a steady fasting blood glucose level with a significant increase in insulin level, considerable restoration of biochemical parameters, and preserved β-cells integrity. Among the different LSF-FA prodrugs, LSF-OA and LSF-PA demonstrated the most favorable physicochemical, systemic pharmacokinetic, and pharmacodynamic profiles.