148579-83-3

Usage

Uses

Used in Organic Synthesis:
(2S,3R,4S,5S,6S)-2-(2-formyl-4-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate is used as a building block for the synthesis of more complex organic compounds. Its multiple functional groups allow for various chemical reactions, enabling the creation of a wide range of molecules with different properties and applications.
Used in Medicinal Chemistry:
In the pharmaceutical industry, (2S,3R,4S,5S,6S)-2-(2-formyl-4-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate is used as a key intermediate in the synthesis of potential drug candidates. Its unique structure and functional groups can be exploited to design molecules with specific biological activities, such as antimicrobial, antiviral, or anticancer properties.
Used in Chemical Research:
(2S,3R,4S,5S,6S)-2-(2-formyl-4-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate is utilized in chemical research to study the reactivity and properties of its functional groups. Understanding its behavior in various chemical reactions can provide insights into the development of new synthetic methods and the discovery of novel compounds with potential applications in various fields.

Upstream product

• 97-51-8 5-Nitrosalicylaldehyde 
• 21085-72-3 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester 
• 63-29-6 D-glucurono-6,3-lactone 
• 7355-18-2 (2S,3S,4S,5R,6S)-3,4,5,6-Tetraacetoxy-tetrahydro-pyran-2-carboxylic acid methyl ester 

Downstream Products

• 1357156-40-1 methyl 1-O-(2-difluoromethyl-4-nitrophenyl)-2,3,4-tri-O-acetyl-β-D-glucopyranuronate 
• 1357156-42-3 methyl 1-O-(2-difluoromethyl-4-aminophenyl)-2,3,4-tri-O-acetyl-β-D-glucopyranuronate 
• 1357156-44-5 methyl 1-O-(2-difluoromethyl-4-aminophenyl)-β-D-glucopyranuronate 

Relevant academic research and scientific papers

GLUCURONIDE PRODRUGS OF TOFACITINIB

The invention relates to glucuronide prodrug compounds of the Janus kinase (JAK) inhibitor tofacitinib having formula (I): (Formula (I)) where A1 and R1 are as defined. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds to treat gastrointestinal inflammatory diseases; and processes and intermediates for preparing such compounds.

GLUCURONIDE PRODRUGS OF JANUS KINASE INHIBITORS

The invention relates to glucuronide prodrug compounds of Janus kinase (JAK) inhibitors having formula I: where W1, R1 and A1 are as defined. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds to treat gastrointestinal inflammatory diseases; and processes and intermediates for preparing such compounds.

Development of a Gd(III)-based receptor-induced magnetization enhancement (RIME) contrast agent for β-glucuronidase activity profiling

β-Glucuronidase is a key lysosomal enzyme and is often overexpressed in necrotic tumor masses. We report here the synthesis of a pro receptor-induced magnetization enhancement (pro-RIME) magnetic resonance imaging (MRI) contrast agent ([Gd(DOTA-FPβGu)]) for molecular imaging of ss-glucuronidase activity in tumor tissues. The contrast agent consists of two parts, a gadolinium complex and a β-glucuronidase substrate (β-D- glucopyranuronic acid). The binding association constant (KA) of [Gd(DOTA-FPβGu)] is 7.42 × 102, which is significantly lower than that of a commercially available MS-325 (KA = 3.0 × 104) RIME contrast agent. The low KA value of [Gd(DOTA-FPβGu)] is due to the pendant β-d-glucopyranuronic acid moiety. Therefore, [Gd(DOTA-FPβGu)] can be used for detection of β-glucuronidase through RIME modulation. The detail mechanism of enzymatic activation of [Gd(DOTA-FPβGu)] was elucidated by LC-MS. The kinetics of β-glucuronidase catalyzed hydrolysis of [Eu(DOTA-FPβGu)] at pH 7.4 best fit the Miechalis-Menten kinetic mode with Km = 1.38 mM, k cat = 3.76 × 103, and kcat/Km = 2.72 × 103 M-1 s-1. The low K m value indicates high affinity of β-glucuronidase for [Gd(DOTA-FPβGu)] at physiological pH. Relaxometric studies revealed that T1 relaxivity of [Gd(DOTA-FPβGu)] changes in response to the concentration of β-glucuronidase. Consistent with the relaxometric studies, [Gd(DOTA-FPβGu)] showed significant change in MR image signal in the presence of β-glucuronidase and HSA. In vitro and in vivo MR images demonstrated appreciable differences in signal enhancement in the cell lines and tumor xenografts in accordance to their expression levels of β-glucuronidase.

An activity-based near-infrared glucuronide trapping probe for imaging β-glucuronidase expression in deep tissues

β-glucuronidase is an attractive reporter and prodrug-converting enzyme. The development of near-IR (NIR) probes for imaging of β-glucuronidase activity would be ideal to allow estimation of reporter expression and for personalized glucuronide prodrug cancer therapy in preclinical studies. However, NIR glucuronide probes are not yet available. In this work, we developed two fluorescent probes for detection of β-glucuronidase activity, one for the NIR range (containing IR-820 dye) and the other for the visible range [containing fluorescein isothiocyanate (FITC)], by utilizing a difluoromethylphenol-glucuronide moiety (TrapG) to trap the fluorochromes in the vicinity of the active enzyme. β-glucuronidase- mediated hydrolysis of the glucuronyl bond of TrapG generates a highly reactive alkylating group that facilitates the attachment of the fluorochrome to nucleophilic moieties located near β-glucuronidase-expressing sites. FITC-TrapG was selectively trapped on purified β-glucuronidase or β-glucuronidase-expressing CT26 cells (CT26/mβG) but not on bovine serum albumin or non-β-glucuronidase-expressing CT26 cells used as controls. β-glucuronidase-activated FITC-TrapG did not interfere with β-glucuronidase activity and could label bystander proteins near β-glucuronidase. Both FITC-TrapG and NIR-TrapG specifically imaged subcutaneous CT26/mβG tumors, but only NIR-TrapG could image CT26/mβG tumors transplanted deep in the liver. Thus NIR-TrapG may provide a valuable tool for visualizing β-glucuronidase activity in vivo.

Prodrugs of anthracyclines for use in antibody-directed enzyme prodrug therapy

A series of new prodrugs of daunorubicin and doxorubicin which are candidates for antibody-directed enzyme prodrug therapy (ADEPT) is reported. These compounds (25a,b,c and 32a,b,c) have been designed to generate cytotoxic drugs after activation with β-gl