1374035-59-2

Upstream product

• 7480-35-5 (1S,2R)-1-amino-2-indanol 
• 1226788-48-2 N¹-(4-chloro-3-fluorophenyl)-N²-((1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)oxalamide 
• 1374035-57-0 N¹-((1S,2S)-2-azido-2,3-dihydro-1H-inden-1-yl)-N²-(4-chloro-3-fluorophenyl)oxalamide 
• 1374035-63-8 (1S,2R)-1-(2-((4-chloro-3-fluorophenyl)amino)-2-oxoacetamido)-2,3-dihydro-1H-inden-2-yl 4-methylbenzenesulfonate 
• 1226789-23-6 ethyl 2-((4-chloro-3-fluorophenyl)amino)-2-oxoacetate 
• 64-18-6 formic acid 
• 1374035-62-7 N¹-((1S,2S)-2-amino-2,3-dihydro-1H-inden-1-yl)-N²-(4-chloro-3-fluorophenyl)oxalamide 
• 4023-02-3 1H-pyrazole-1-carboximidamide hydrochloride 

Relevant academic research and scientific papers

CD4-MIMETIC INHIBITORS OF HIV-1 ENTRY AND METHODS OF USE THEREOF

Described herein are small-molecule mimics of CD4, which both enter the Phe43 cavity and target Asp368 of gpl20, the HIV-1 envelope protein. Also described herein are methods of using these compounds to inhibit the transmission or progression of HIV infection. These compounds exhibit antiviral potency greater than that of a known antiviral, NBD-556, with 100% breadth against clade B and C viruses. Importantly, the compounds do not activate HIV infection of CD4-negative, CCR5-positive cells, in contrast to NBD- 556.

Structure-based design, synthesis, and characterization of dual hotspot small-molecule HIV-1 Entry Inhibitors

Cellular infection by HIV-1 is initiated with a binding event between the viral envelope glycoprotein gp120 and the cellular receptor protein CD4. The CD4-gp120 interface is dominated by two hotspots: a hydrophobic gp120 cavity capped by Phe43CD4 and an electrostatic interaction between residues Arg59CD4 and Asp368gp120. The CD4 mimetic small-molecule NBD-556 (1) binds within the gp120 cavity; however, 1 and related congeners demonstrate limited viral neutralization breadth. Herein, we report the design, synthesis, characterization, and X-ray structures of gp120 in complex with small molecules that simultaneously engage both binding hotspots. The compounds specifically inhibit viral infection of 42 tier 2 clades B and C viruses and are shown to be antagonists of entry into CD4-negative cells. Dual hotspot design thus provides both a means to enhance neutralization potency of HIV-1 entry inhibitors and a novel structural paradigm for inhibiting the CD4-gp120 protein-protein interaction.