- Modular construction of quaternary hemiaminal-based inhibitor candidates and their in cellulo assessment with HIV-1 protease
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Non-peptidomimetic drug-like protease inhibitors have potential for circumventing drug resistance. We developed a much-improved synthetic route to our previously reported inhibitor candidate displaying an unusual quaternized hemi-aminal. This functional group forms from a linear precursor upon passage into physiological media. Seven variants were prepared and tested in cellulo with our HIV-1 fusion-protein technology that result in an eGFP-based fluorescent readout. Three candidates showed inhibition potency above 20 μM and toxicity at higher concentrations, making them attractive targets for further refinement. Importantly, our class of original inhibitor candidates is not recognized by two major multidrug resistance pumps, quite in contrast to most clinically applied HIV-1 protease inhibitors.
- Gros, Guillaume,Martinez, Lorena,Gimenez, Anna Servat,Adler, Paula,Maurin, Philippe,Wolkowicz, Roland,Falson, Pierre,Hasserodt, Jens
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supporting information
p. 5407 - 5413
(2013/09/02)
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- Resolution and absolute configuration of some a-aminoacetals: En route to enantiopure N-protected a-aminoaldehydes
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The first successful resolution of rac-a-aminoacetals via diastereoisomeric salt formation with optically pure N-protected aminoacids is reported. The absolute configuration assignment of a-aminoacetal enantiomers is performed by an entirely non-racemizing chemical correlation method involving N-protection and a new efficient hydrolysis step followed by a reduction of the resulting N-protected a-aminoaldehyde intermediates. A racemization method of optically enriched a-aminoacetals is exemplified to allow valorisation of both enantiomers. Springer-Verlag 2011.
- Albalat-Serradeil, Muriel,Primazot, Geraldine,Wilhelm, Didier,Vallejos, Jean-Claude,Vanthuyne, Nicolas,Roussel, Christian
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p. 687 - 696
(2012/09/22)
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- PROCESS FOR PREPARING ALPHA AMINOACETALS IN RECEMIC FORM
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The invention relates to a process for preparing an α-aminoacetal, or addition salts thereof, of formula (I) in recemic form comprising the steps consisting in: reacting a glyoxal monoacetal of formula (II) with an arylalkylamine of formula (III) in such a way as to obtain an imine of formula (IV); adding a Grignard reagent of formula R3-Mg-HaI to said imine of formula (IV) so as to obtain an amine of formula (V), and - deprotecting the amine of formula (V) in such a way as to obtain the compound of formula (I) in racemic form, and, where appropriate, adding an inorganic or organic acid in order to obtain an addition salt of the α-aminoacetal of formula (I).
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Page/Page column 17-18
(2010/04/25)
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- PROCESS OF PREPARATION OF OPTICALLY ACTIVE ALPHA AMINOACETALS
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The invention relates to a process for preparing optically active α-aminoacetals by resolution of a racemic mixture or of a mixture of enantiomers via the formation of diastereoisomeric salts, and also novel intermediates in the form of diastereoisomeric
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Page/Page column 22
(2009/10/21)
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- Diversity-oriented synthesis of a drug-like system displaying the distinctive N→C=O interaction
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(Chemical Equation Presented) This study describes the syntheses and characterization of two hydrazino ureas. These fold into a six-membered ring by virtue of the infrequently observed δ+N→C=O δ- interaction when solvated by polar pr
- Waibel, Michael,Hasserodt, Jens
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p. 6119 - 6126
(2008/12/22)
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- PROCESS OF RACEMISATION OF OPTICALLY ACTIVE ALPHA AMINOACETALS
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The invention relates to a process for preparing α-aminoacetals substantially in racemic form, comprising a step of oxidizing optically enriched α-aminoacetals to the corresponding oximes, in the presence of a catalyst, and a step of reducing the oximes t
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Page/Page column 11-12
(2009/01/20)
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- Solid-phase synthesis of C-terminal peptide aldehydes from amino acetals anchored to a backbone amide linker (BAL) handle
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Peptide aldehydes were synthesized, starting from amino acetals, by a Solid-phase backbone amide linker (BAL) strategy. (C) 2000 Elsevier Science Ltd.
- Guillaumie,Kappel,Kelly,Barany,Jensen
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p. 6131 - 6135
(2007/10/03)
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