333353-44-9

Usage

Uses

Used in Pharmaceutical Industry:
NBD-556 is used as an HIV-1 entry inhibitor for its ability to block the gp120-CD4 interaction, which is crucial for the virus to enter human cells. This makes it a potential candidate for the development of antiretroviral therapies to combat HIV-1 infection.

Biological Activity

the entry of hiv-1 into host cells is mediated by the binding of the surface subunit gp120 to the host cell receptor cd4. nbd-556 is a novel class of human immunodeficiency virus type 1 (hiv-1) entry inhibitor that block the gp120–cd4 interaction with drug-like properties.

in vitro

a systematic study showed that nbd-556 and nbd-557 target viral entry by inhibiting the binding of hiv-1 envelope glycoprotein gp120 to the cellular receptor cd4 but did not inhibit reverse transcriptase, protease, or integrase, demonstrating that they do not target the later stages of the hiv-1 life cycle to inhibit hiv-1 infection. nbd-556 and nbd-557 were also active against hiv-1 laboratory-adapted strains including an azt-resistant strain and hiv-1 primary isolates, showing that these compounds can potentially be further modified to become potent hiv-1 entry inhibitors [1].

IC 50

nbd-556 inhibited cell–cell fusion between h9/hiv-1iiib and mt-2 (ic50 ~3 μm)

references

[1] zhao, q. , l. ma, s. jiang, h. lu, s. liu, y. he, n. strick, n. neamati, and a. k. debnath. 2005. identification of n-phenyl-n′-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of hiv-1 entry inhibitors that prevent gp120 binding to cd4. virology 339:213-225.

Upstream product

• 36768-62-4 4-AMINO-2,2,6,6-TETRAMETHYLPIPERIDINE 
• 5397-14-8 ethyl 2-[(4-chlorophenyl)amino]-2-oxoacetate 
• 106-47-8 4-chloro-aniline 
• 17738-71-5 2-((4-chlorophenyl)-amino)-2-oxoacetic acid 

Relevant academic research and scientific papers

2,2,2-Trifluoroethyl Chlorooxoacetate-Universal Reagent for One-Pot Parallel Synthesis of N1-Aryl-N2-alkyl-Substituted Oxamides

A one-pot parallel synthesis of N1-aryl-N2-alkyl-substituted oxamides with 2,2,2-trifluoroethyl chlorooxoacetate was developed. The synthesis of a library of 45 oxamides revealed higher efficiency of this reagent over the known ethyl chlorooxoacetate. The reagent was successfully used to prepare the known oxamide-containing HIV entry inhibitors.

Design, synthesis, and antiviral activity of entry inhibitors that target the CD4-binding site of HIV-1

The CD4 binding site on HIV-1 gp120 has been validated as a drug target to prevent HIV-1 entry to cells. Previously, we identified two small molecule inhibitors consisting of a 2,2,6,6-tetramethylpiperidine ring linked by an oxalamide to a p-halide-substituted phenyl group, which target this site, specifically, a cavity termed "Phe43 cavity". Here we use synthetic chemistry, functional assessment, and structure-based analysis to explore variants of each region of these inhibitors for improved antiviral properties. Alterations of the phenyl group and of the oxalamide linker indicated that these regions were close to optimal in the original lead compounds. Design of a series of compounds, where the tetramethylpiperidine ring was replaced with new scaffolds, led to improved antiviral activity. These new scaffolds provide insight into the surface chemistry at the entrance of the cavity and offer additional opportunities by which to optimize further these potential-next- generation therapeutics and microbicides against HIV-1.

Rapid microwave-assisted syntheses of derivatives of HIV-1 entry inhibitors

The direct amidation of esters with 4-amino-2,2,6,6-tetramethylpiperidine was achieved by computer-controlled microwave irradiation in toluene. The microwave protocol allowed the new amides to be prepared in three hours rather than the three days required by traditional thermal methods. Georg Thieme Verlag Stuttgart.