2095551-10-1

Basic information

• Product Name: (S)-isopropyl 2-(((S)-(((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-di-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino) propanoate
• CAS NO: 2095551-10-1
• Molecular Weight: 527.468
• Mol File: 2095551-10-1.mol
• Article Data: 6

Chemical Properties

• CAS DataBase Reference: (S)-isopropyl 2-(((S)-(((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-di-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino) propanoate(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-isopropyl 2-(((S)-(((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-di-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino) propanoate(2095551-10-1)
• EPA Substance Registry System: (S)-isopropyl 2-(((S)-(((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-di-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino) propanoate(2095551-10-1)

Safety Data

• Hazardous Substances Data: 2095551-10-1(Hazardous Substances Data)

Usage

General Description

The chemical compound "(S)-isopropyl 2-(((S)-(((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino) propanoate" is a complex organic molecule. It is composed of various functional groups such as isopropyl, amino, phosphoryl, and carboxyl, arranged in a specific configuration. The compound also contains substructures such as dioxo, dihydroxy, and tetrahydrofuran, which contribute to its overall chemical properties and interactions. (S)-isopropyl 2-(((S)-(((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-di-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino) propanoate may have potential applications in pharmaceuticals, biotechnology, or other fields due to its intricate structure and potential biological activities.

Upstream product

• 1334513-02-8 (S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester 
• 31448-54-1 2'-C-methyluridine 
• 1337529-56-2 (S)-2-[(S)-(2,3,4,5,6-pentafluoro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester 
• 1365634-46-3 2'-methyluridine 
• 1256490-52-4 (S)-2-[(2,3,4,5,6-pentafluorophenoxy)phenoxyphosphorylamino]propionic acid isopropyl ester 
• 114262-49-6 1-(2'-C-methyl-β-D-arabinofuranosyl)uracil 
• 39825-33-7 isopropyl L-alanine 
• 770-12-7 O-phenyl phosphorodichloridate 

Relevant articles and documents

Development and validation of a phenotypic high-content imaging assay for assessing the antiviral activity of small-molecule inhibitors targeting zika virus

Zika virus (ZIKV) has been linked to the development of microcephaly in newborns, as well as Guillain-Barré syndrome. There are currently no drugs available to treat ZIKV infection, and accordingly, there is an unmet medical need for the discovery of new therapies. High-throughput drug screening efforts focusing on indirect readouts of cell viability are prone to a higher frequency of false positives in cases where the virus is viable in the cell but the cytopathic effect (CPE) is reduced or delayed. Here, we describe a fast and label-free phenotypic high-content imaging assay to detect cells affected by the virus-induced CPE using automated imaging and analysis. Protection from the CPE correlates with a decrease in viral antigen production, as observed by immunofluorescence. We trained our assay using a collection of nucleoside analogues with activity against ZIKV; the previously reported antiviral activities of 2=-C-methylribonucleosides and ribavirin against the Zika virus in Vero cells were confirmed using our developed method. To validate the ability of our assay to reveal new anti-ZIKV compounds, we profiled a novel library of 24 natural product derivatives and found compound 1 to be an inhibitor of the ZIKVinduced cytopathic effect; the activity of the compound was confirmed in human fetal neural stem cells (NSCs). The described technique can be easily leveraged as a primary screening assay for profiling of the activities of large compound libraries against ZIKV and can be expanded to other ZIKV strains and other cell lines displaying morphological changes upon ZIKV infection.

Synthesis and biological evaluation of 5′-C-methyl nucleotide prodrugs for treating HCV infections

Nucleotide prodrugs are of great clinical interest for treating a variety of viral infections due to their ability to target tissues selectively and to deliver relatively high concentrations of the active nucleotide metabolite intracellularly. However, their clinical successes have been limited, oftentimes due to unwanted in vivo metabolic processes that reduce the quantities of nucleoside triphosphate that reach the site of action. In an attempt to circumvent this, we designed novel nucleosides that incorporate a sterically bulky group at the 5′-carbon of the phosphoester prodrug, which we reasoned would reduce the amounts of non-productive P[sbnd]O bond cleavage back to the corresponding nucleoside by nucleotidases. Molecular docking studies with the NS5B HCV polymerase suggested that a nucleotide containing a 5′-methyl group could be accommodated. Therefore, we synthesized mono- and diphosphate prodrugs of 2′,5′-C-dimethyluridine stereoselectively and evaluated their cytotoxicity and anti-HCV activity in the HCV replicon assay. All four prodrugs exhibited anti-HCV activity with IC50 values in the single digit micromolar concentrations, with the 5′(R)-C-methyl prodrug displaying superior potency relative to its 5′(S)-C-methyl counterpart. However, when compared to the unmethylated prodrug, the potency is poorer. The poorer potency of these prodrugs may be due to unfavorable steric interactions of the 5′-C-methyl group in the active sites of the kinases that catalyze the formation of active triphosphate metabolite.

Mechanism-Based Solution to the ProTide Synthesis Problem: Selective Access to Sofosbuvir, Acelarin, and INX-08189

A general and efficient method for the synthesis of pronucleotide (ProTide) 5'-phosphoramidate monoesters is reported. This method consists of a highly stereoselective 5'-phosphorylation mediated by dimethylaluminum chloride to afford the desired target ProTides in excellent yields without employing 3'-protection strategies. The application of this methodology to the synthesis of a number of pharmaceutically relevant compounds currently marketed or under investigation in clinical research is demonstrated.