95480-61-8

Upstream product

• 97-53-0 4-allylguaiacol 
• 2616-64-0 UDP-glucuronic acid 
• 1245697-26-0 UDP-glucuronic acid 
• 92420-89-8 methyl 2,3,4-tri-O-acetyl-1-O-(trichloroacetimidoyl)-α-D-glucopyranuronate 

Relevant academic research and scientific papers

o-Methoxy-4-alkylphenols that form quinone methides of intermediate reactivity are the most toxic in rat liver slices

The effects of p-alkyl substituents on the relative cytotoxicity of 4- alkyl-2-methoxyphenols were investigated in isolated rat liver slices. The derivatives of 4-alkyl-2-methoxyphenol studied were 4-methyl- (creosol), 4- ethyl-, 4-propyl-, 4-isopropyl-, 4-allyl-2-methoxyphenol (eugenol), as well as 4-allyl-2,6-dimethoxyphenol. The data were correlated with previous microsomal experiments which showed that all of the 4-alkyl-2-methoxyphenols were converted to quinone methides (QMs; 4-methylene-2,5-cyclohexadien-1- ones) via a cytochrome P450-catalyzed process [Bolton, J. L., Comeau, E., and Vukomanovic, V. (1995) Chem.-Biol. Interact., in press]. The present investigation showed little correlation between the rate of QM formation in microsomes and the relative toxicities of the alkylphenols, unless the QMs formed were of similar reactivity. In contrast, a plot of alkylphenol toxicity versus the relative hydrolysis rates of QMs derived from these phenols fit a parabolic equation with a minimum at the data for 4-isopropyl- 2-methoxyphenol. These data suggest that in vivo oxidation of phenols to QMs which have lifetimes in the 10 s-10 min range results in cytotoxicity. QMs with reactivities outside this window are less toxic since the electrophile is either too stable for reaction with cellular nucleophiles or too reactive for nucleophilic cellular macromolecules to compete with solvent. These data suggest that a reactivity window exists for QMs which is a primary determinant of the extent of cytotoxic injury caused by these reactive electrophiles.

Synthesis of four eugenol metabolites

Four eugenol metabolites were concisely synthesized and their structures were confirmed by1H-NMR,13C-NMR and high-resolution mass (HR-MS). Among them, the synthesis of eugenol-β-D-glucuronide (3) and eugenol sulfate (4) was reported for the first time. The successful synthesis of the four eugenol metabolites provides a material basis for further metabolic study of prodrug aspirin euge-nol ester (AEE).

Two metabolites of aspirin eugenol ester and preparation method thereof

The invention provides two metabolites M1 and M2 of aspirin eugenol ester. A chemical structural formula is as follows: (the formula is shown in the description). M1 is prepared by adopting pyridine as an alkali-binding agent and a solvent by virtue of th

Accurate prediction of glucuronidation of structurally diverse phenolics by human UGT1A9 using combined experimental and in silico approaches

Purpose: Catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics, was determined experimentally using 145 phenolics and analyzed by 3D-QSAR methods. Methods: Catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using CoMFA and CoMSIA techniques. Molecular alignment of substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered a separate substrate. Results: 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q 2=0.548, r2=0.949, r pred 2 =0.775; CoMSIA: q2=0.579, r2=0.876, rpred2 =0.700). Contour coefficient maps were applied to elucidate structural features among substrates that are responsible for selectivity differences. Contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9, enabling identification of the UGT1A9 catalytic pocket with a high degree of confidence. Conclusion: CoMFA/CoMSIA models can predict substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and substrate selectivity.