59085-15-3Relevant articles and documents
Scaffold Simplification Strategy Leads to a Novel Generation of Dual Human Immunodeficiency Virus and Enterovirus-A71 Entry Inhibitors
Martínez-Gualda, Belén,Sun, Liang,Martí-Marí, Olaia,Noppen, Sam,Abdelnabi, Rana,Bator, Carol M.,Quesada, Ernesto,Delang, Leen,Mirabelli, Carmen,Lee, Hyunwook,Schols, Dominique,Neyts, Johan,Hafenstein, Susan,Camarasa, María-José,Gago, Federico,San-Félix, Ana
, p. 349 - 368 (2020)
Currently, there are only three FDA-approved drugs that inhibit human immunodeficiency virus (HIV) entry-fusion into host cells. The situation is even worse for enterovirus EV71 infection for which no antiviral therapies are available. We describe here the discovery of potent entry dual inhibitors of HIV and EV71. These compounds contain in their structure three or four tryptophan (Trp) residues linked to a central scaffold. Critical for anti-HIV/EV71 activity is the presence of extra phenyl rings, bearing one or two carboxylates, at the C2 position of the indole ring of each Trp residue. The most potent derivatives, 22 and 30, inhibit early steps of the replicative cycles of HIV-1 and EV-A71 by interacting with their respective viral surfaces (glycoprotein gp120 of HIV and the fivefold axis of the EV-A71 capsid). The high potency, low toxicity, facile chemical synthesis, and great opportunities for chemical optimization make them useful prototypes for future medicinal chemistry studies.
Construction of a well-defined multifunctional dendrimer for theranostics
Ornelas, Catia,Pennell, Ryan,Liebes, Leonard F.,Weck, Marcus
supporting information; scheme or table, p. 976 - 979 (2011/04/25)
A dendrimer-based building block for theranostics was designed. The multifunctional dendrimer is polyamide-based and contains nine azide termini, nine amine termini, and fifty-four terminal acid groups. Orthogonal functionalization of the multifunctional
Strain-promoted alkyne azide cycloaddition for the functionalization of poly(amide)-based dendrons and dendrimers
Ornelas, Catia,Broichhagen, Johannes,Weck, Marcus
supporting information; experimental part, p. 3923 - 3931 (2010/05/15)
Functionalization of a poly(amido)-based dendron with ethylene glycol chains (PEG) using coppercatalyzed alkyne azide cycloaddition (CuAAC) afforded dendrons with significant levels of copper contaminations, preventing the use of such materials for biological applications. We suggest that the presence of amide, PEG, and triazole functional groups allows for copper complexation, thereby preventing the separation of the copper catalyst from the final dendron. To minimize this problem, synthetic variations on CuAAC including the addition of "click" additives for copper sequestering as well as the use of copper wire as the copper source were investigated. None of these strategies, however, resulted in copper-free products. In contrast, we developed a copper-free strain-promoted alkyne azide cycloaddition (SPAAC) strategy that functionalized poly(amide)-based dendrons and dendrimers with PEG chains quantitatively under mild reaction conditions without any metal contamination. The SPAAC products were characterized by 1H and 13C NMR, 2D HSQC and COSY NMR, mass spectrometry, and elemental analysis. This is the first report on the use of SPAAC for dendrimer functionalization, and the results obtained here show that SPAAC is an important tool to the dendrimer and more general biomaterials community for the functionalization of macromolecular structures due to the mild and metal-free reaction conditions, no side products, tolerance toward functional groups, and high yields.
