698358-03-1

Usage

Uses

Used in Pharmaceutical Industry:
ALLYL D-GLUCURONATE is used as an intermediate in the efficient synthesis of 1β-O-acyl glucuronides, which are known metabolites of important drugs. This application is crucial for the development of new drugs and the improvement of existing ones, as it allows for the creation of more effective and targeted therapies.
Used in Drug Metabolism Research:
ALLYL D-GLUCURONATE is used as a research tool for studying the metabolism of drugs and their glucuronidation pathways. Understanding these pathways is essential for predicting drug interactions, side effects, and overall safety, as well as for optimizing drug dosing and efficacy.

Upstream product

• 6556-12-3 D-glucuronic acid 
• 106-95-6 allyl bromide 
• 104195-06-4 L-glucuronic acid 
• 912483-14-8 galacturonic acid 
• 489-91-8 D-glucuronic acid 
• 6556-12-3 D-Glucuronic acid 

Downstream Products

• 1184951-57-2 allyl 6-([4-([1-(tert-butyl)-1,1-dimethylsilyl]oxymethyl)anilino]carbonyloxy)-3,4,5-trihydroxytetrahydro-2H-2-pyrancarboxylate 
• 190605-03-9 rhein acyl glucuronide 
• 1414867-53-0 1-O-({trans-4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl]cyclohexyl}acetyl)-β-D-glucopyranuronic acid 

Relevant academic research and scientific papers

Plasma stability-dependent circulation of acyl glucuronide metabolites in humans: How circulating metabolite profiles of muraglitazar and peliglitazar can lead to misleading risk assessment

Muraglitazar and peliglitazar, two structural analogs differing by a methyl group, are dual peroxisome proliferator-activated receptor- α/γ activators. Both compounds were extensively metabolized in humans through acyl glucuronidation to form 1-O-β-acyl g

UGT-dependent regioselective glucuronidation of ursodeoxycholic acid and obeticholic acid and selective transport of the consequent acyl glucuronides by OATP1B1 and 1B3

Ursodeoxycholic acid (UDCA) is a major effective constituent of bear bile powder, which is widely used as function food in China and is documented in the Chinese pharmacopoeia as a traditional Chinese medicine. UDCA has been developed as the only accepted therapy by the US FDA for primary biliary cholangitis. Recently, the US FDA granted accelerated approval to obeticholic acid (OCA), a semisynthetic bile acid derivative from chenodeoxycholic acid, for primary biliary cholangitis. However, some perplexing toxicities of UDCA have been reported in the clinic. The present work aimed to investigate the difference between UDCA and OCA in regard to potential metabolic activation through acyl glucuronidation and hepatic accumulation of consequent acyl glucuronides. Our results demonstrated that the metabolic fates of UDCA and OCA were similar. Both UDCA and OCA were predominantly metabolically activated by conjugation to the acyl glucuronide in human liver microsomes. UGT1A3 played a predominant role in the carboxyl glucuronidation of both UDCA and OCA, while UGT2B7 played a major role in their hydroxyl glucuronidation. Further uptake studies revealed that OATP1B1- and 1B3-transfected cells could selectively uptake UDCA acyl glucuronide, but not UDCA, OCA, and OCA acyl glucuronide. In summary, the liver disposition of OCA is different from that of UDCA due to hepatic uptake, and liver accumulation of UDCA acyl glucuronide might be related to the perplexing toxicities of UDCA.

The practical synthesis of β-acyl glucuronides by using allyl 2,3,4-tri-(O-allyloxycarbonyl)-D-glucuronate and 1-chloro-N,N,2-trimethyl-1-propenylamine

We described the practical synthesis of β-acyl glucuronide from allyl 2,3,4-tri-(O-allyloxycarbonyl)-D-glucuronate (5) mediated by 1-chloro-N,N,2-trimethyl-1-propenylamine (TMCE). A wide range of bulky carboxylic acids (aryl carboxylic acids or tertiary-carbon-linked carboxylic acids) were employed to give the corresponding β-acyl glucuronate in good yields. The side products of this reaction are only N,N-dimethylisobutyramide and HCl. As the resulting acyl glucuronates show sufficient solubility to organic solvent, it can be easily purified by conventional silica gel column chromatography and/or crystallization, even in multigram quantities. The allyloxycarbonyl group and allyl group are cleanly removed by Pd(0), and thus the protocol can provide multigram quantities of β-acyl glucuronides with high purity.

HETEROCYCLIC COMPOUNDS AND METHODS OF THEIR USE

The present invention relates generally to compounds that are useful in antagonizing the angiotensin II type 2 (AT2) receptor. More particularly, the invention relates to substituted isoquinoline compounds and their use as AT2 receptor antagonists. Pharmaceutical compositions comprising the compounds and their use in modulating the AT2 receptor and therapies that require modulation of the AT2 receptor are described.

Synthesis of three isotopically labeled versions and a metabolite of Aurora A kinase inhibitor

Sodium ring-[14C]-4-[[9-chloro-7-(2,6-difluorophenyl)-5H- pyrimido[5,4-d][2]benzazepin-2-yl]amino]-benzoate (1A, MLN8054), an Aurora A kinase inhibitor, was synthesized from [14C]-cyanamide in two steps in an overall radiochemical yi

Synthesis of betulinic acid acyl glucuronide for application in anticancer prodrug monotherapy

The synthesis of 28-O-β-d-glucuronide betulinic acid, an acyl glucuronide derivative, was successfully carried out for the first time using commercially available peracetylated methyl glucuronate bromide under phase-transfer conditions. The target compound could be used in an anticancer prodrug monotherapy (PMT) strategy since it is non-cytotoxic, non-haemolytic, more water soluble than betulinic acid, it possesses a good in vitro stability in phosphate buffer and can be hydrolyzed in the presence of β-d-glucuronidase releasing in vitro betulinic acid, a promising anticancer agent.

Efficient synthesis of 1β-O-acyl glucuronides via selective acylation of allyl or benzyl d-glucuronate

Acyl glucuronides are key metabolites for many carboxylic acid-containing drugs, notably those of the non-steroidal anti-inflammatory class. In the processes of drug safety assessment and new drug development, it is essential that acyl glucuronides, if formed in vivo, should be made conveniently available for bioevaluation. We recently showed that selective acylation of allyl glucuronate is a promising method for the synthesis of these metabolites in good yield and with excellent β-anomeric selectivity. We now give fuller details of the allyl ester method and further report that benzyl glucuronate performs at least equally well in the acylation step, offering the advantage of very mild deprotection by catalytic transfer (or conventional) hydrogenation. Depending on the compatibility of other functional groups, as discussed below, this will be the method of choice for many acyl glucuronide syntheses. The value of the method is demonstrated in particular by the synthesis of several acyl glucuronides that are known metabolites of important drugs.

Protecting groups for glucuronic acid: Application to the synthesis of new paclitaxel (taxol) derivatives

To prepare two new glucuronide conjugates, allyl ester and allyl carbonates were used as protecting groups of the glucuronic moiety. In this way, an aniline glycosyl carbamate spacer linked to the 2′-OH of paclitaxel was obtained. By using palladium chemistry, an efficient one-step removal of all the allyl groups at the end of the synthesis afforded the desired compounds in good yields.

LONIDAMINE ANALOGS

Lonidamine analogs are useful in the treatment of cancer and BPH.

Syntheses and characterization of the acyl glucuronide and hydroxy metabolites of diclofenac

In humans, metabolism of the commonly used nonsteroidal antiinflammatory drug diclofenac 1 yields principally the 4′-hydroxy 2, 5-hydroxy 3, and acyl glucuronide 4 metabolites. All three metabolites have been implicated in rare idiosyncratic adverse react