- Promiscuity and selectivity in covalent enzyme inhibition: A systematic study of electrophilic fragments
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Covalent ligand-target interactions offer significant pharmacological advantages. However, off-target reactivity of the reactive groups, which usually have electrophilic properties, must be minimized, and the selectivity of irreversible inhibitors is a crucial requirement. We therefore performed a systematic study to determine the selectivity of several electrophilic groups that can be used as building blocks for covalently binding ligands. Six reactive groups with modulated electrophilicity were combined with 11 nonreactive moieties, resulting in a small combinatorial library of 72 fragment-like compounds. These compounds were screened against a group of 11 enzyme targets to assess their selectivity and their potential for promiscuous binding to proteins. The assay results showed a considerably lower degree of promiscuity than initially expected, even for those members of the screening collection that contain supposedly highly reactive electrophiles.
- J?st, Christian,Nitsche, Christoph,Scholz, Therese,Roux, Lionel,Klein, Christian D.
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supporting information
p. 7590 - 7599
(2014/12/11)
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- Interaction of 2-naphthol with γ-ureidoacetals. A new method for the synthesis of 2-arylpyrrolidines
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We report a new, single-stage method for the synthesis of 2-arylpyrrolidines, based on an acid-catalyzed reaction of 2-naphthol with γ-ureidoacetals, enabling the preparation of the target compounds under mild conditions, while avoiding costly reagents an
- Gazizov,Smolobochkin,Burilov,Pudovik
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p. 707 - 714
(2014/08/18)
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- Reaction of 1-aryl-3-(4,4-diethoxybutyl)ureas with phenols. Synthesis of 2-arylpyrrolidines
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Acid-catalyzed reaction of phenols with 1-(4,4-diethoxybutyl)urea derivatives gave new 2-arylpyrrolidines containing 4-bromoresorcinol and hydroquinone fragments. The described reaction is advantageous due to its mild conditions and no necessity of using
- Gazizov, A. S.,Burilov, A. R.,Pudovik, M. A.,Smolobochkin, A. V.
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p. 1809 - 1813
(2015/02/02)
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- REACTIONS OF ISOTHIOCYANATES AND ISOCYANATES WITH SOME SILYLATED NITROGEN-CONTAINING NUCLEOPHILES
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Aryl isothiocyanates and arylisocyanates react with N,O-bis(trimethylsilyl)acetamide to give N-methyl-N'-arylthioureas and ureas.Also nucleophilic additions of other aprotic nucleophiles (e.g.N-trimethylsilylimidazole, N-trimethylsilylpiperidine and N-trimethylsilylmorpholine) to the N=C=X (X=O,S) group were investigated.
- Gonda, Josef,Antalova, Zuzana
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p. 685 - 694
(2007/10/02)
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