- Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2
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Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PLpro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS-CoV PLpro. Moreover, we report the discovery of isoindolines as a new class of potent PLpro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PLpro are valuable starting points for the development of new pan-coronaviral inhibitors.
- Welker, Armin,Kersten, Christian,Müller, Christin,Madhugiri, Ramakanth,Zimmer, Collin,Müller, Patrick,Zimmermann, Robert,Hammerschmidt, Stefan,Maus, Hannah,Ziebuhr, John,Sotriffer, Christoph,Schirmeister, Tanja
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supporting information
p. 340 - 354
(2020/10/19)
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- A novel amino-benzosuberone derivative is a picomolar inhibitor of mammalian aminopeptidase N/CD13
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A new class of low molecular weight, highly potent and selective non peptidic inhibitors of aminopeptidase N (APN/CD13) is described. We report the synthesis and in vitro evaluation of racemic substituted analogues of 7-amino-benzocyclohepten-6-one 1a. We
- Maiereanu, Carmen,Schmitt, Céline,Schifano-Faux, Nadge,Le Nou?n, Didier,Defoin, Albert,Tarnus, Céline
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experimental part
p. 5716 - 5733
(2011/10/12)
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- Benzazepine Compound
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[Problem] Provided is a compound which is useful as an agent for treating or preventing 5-HT2C receptor-related diseases, particularly incontinence such as stress urinary incontinence, urge urinary incontinence, mixed urinary incontinence, and
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Page/Page column 14
(2011/11/12)
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- 2-[2H-(1,3-dihydroisoindole)alkylene]-4,5-dihydroimidazoles and pharmaceutical compositions thereof
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A compound of formula (I): STR1 or a pharmaceutically acceptable salt, ester or amide thereof, wherein: Z represents a residue of a substituted or unsubstituted aryl group, X represents O or NRo wherein Ro represents a hydrogen atom,
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- Isoindolinyl derivatives
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Esters of lower alkanoic acids substituted at the α-position with isoindoline or tetrahydroisoquinoline, and intermediates therefor, useful as pesticides.
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