0000000001035078
AUTHOR
Max Rieger
Protocol for rational design of covalently interacting inhibitors.
The inhibition potencies of covalent inhibitors mainly result from the formation of a covalent bond to the enzyme during the inhibition mechanism. This class of inhibitors has essentially been ignored in previous target-directed drug discovery projects because of concerns about possible side effects. However, their advantages, such as higher binding energies and longer drug-target residence times moved them into the focus of recent investigations. While the rational design of non-covalent inhibitors became standard the corresponding design of covalent inhibitors is still in its early stages. Potent covalent inhibitors can be retrieved from large compound libraries by covalent docking approa…
Vinyl sulfone building blocks in covalently reversible reactions with thiols
In the present study we use quantum-chemical calculations to investigate how the reactivity of vinyl sulfone-based compounds can be modified from an irreversible to a reversible reaction with thiols. Based on the predictions from theory, an array of nine different vinyl sulfones with systematically varying substitution pattern was synthesized and their crystal structures were determined. Subsequent Hirshfeld surface analyses employing the principle of electrostatic complementarity aid the understanding of the crystal packing of the synthesized compounds. Reactivity studies against the nucleophile 2-phenylethanethiol mirror the properties predicted by the quantum-chemical computations in sol…
CCDC 897063: Experimental Crystal Structure Determination
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 897056: Experimental Crystal Structure Determination
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 897057: Experimental Crystal Structure Determination
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 897062: Experimental Crystal Structure Determination
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 897061: Experimental Crystal Structure Determination
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 897060: Experimental Crystal Structure Determination
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 897059: Experimental Crystal Structure Determination
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 897058: Experimental Crystal Structure Determination
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G