Abstract
The synthesis of novel coumarins bearing on the lateral side chain in the 3-position an amine or a guanidine group is described. In vitro evaluation highlighted 14d which possesses a meta aniline side chain as a very potent THR inhibitor. Surprisingly, the introduction of a guanidine moiety always led to a decrease in THR inhibiting properties. We, thus, used docking experiments to rationalize the SAR in the series. This study showed the crucial role of a conserved water molecule in the specificity pocket of THR during docking simulation in order to explain the inactivity of guanidine derivatives. © 2006 Elsevier Ltd. All rights reserved.
Original language | English |
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Pages (from-to) | 2017-2021 |
Number of pages | 5 |
Journal | Bioorganic and medicinal chemistry letters |
Volume | 16 |
Issue number | 7 |
DOIs | |
Publication status | Published - 1 Apr 2006 |
Keywords
- Coumarins
- Docking
- Mechanism-based inhibitor
- Serine protease
- Thrombin
Fingerprint Dive into the research topics of 'Investigation of mechanism-based thrombin inhibitors: Implications of a highly conserved water molecule for the binding of coumarins within the S pocket'. Together they form a unique fingerprint.
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Mass Spectrometry Service
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