0000000001305766
AUTHOR
Robert Abel
Prospective Evaluation of Free Energy Calculations for the Prioritization of Cathepsin L Inhibitors.
Improving the binding affinity of a chemical series by systematically probing one of its exit vectors is a medicinal chemistry activity that can benefit from molecular modeling input. Herein, we compare the effectiveness of four approaches in prioritizing building blocks with better potency: selection by a medicinal chemist, manual modeling, docking followed by manual filtering, and free energy calculations (FEP). Our study focused on identifying novel substituents for the apolar S2 pocket of cathepsin L and was conducted entirely in a prospective manner with synthesis and activity determination of 36 novel compounds. We found that FEP selected compounds with improved affinity for 8 out of …
CCDC 1516759: Experimental Crystal Structure Determination
Related Article: Bernd Kuhn, Michal Tichý, Lingle Wang, Shaughnessy Robinson, Rainer E. Martin, Andreas Kuglstatter, Jörg Benz, Maude Giroud, Tanja Schirmeister, Robert Abel, François Diederich, and Jérôme Hert|2017|J.Med.Chem.|60|2485|doi:10.1021/acs.jmedchem.6b01881
CCDC 1516760: Experimental Crystal Structure Determination
Related Article: Bernd Kuhn, Michal Tichý, Lingle Wang, Shaughnessy Robinson, Rainer E. Martin, Andreas Kuglstatter, Jörg Benz, Maude Giroud, Tanja Schirmeister, Robert Abel, François Diederich, and Jérôme Hert|2017|J.Med.Chem.|60|2485|doi:10.1021/acs.jmedchem.6b01881
CCDC 1516761: Experimental Crystal Structure Determination
Related Article: Bernd Kuhn, Michal Tichý, Lingle Wang, Shaughnessy Robinson, Rainer E. Martin, Andreas Kuglstatter, Jörg Benz, Maude Giroud, Tanja Schirmeister, Robert Abel, François Diederich, and Jérôme Hert|2017|J.Med.Chem.|60|2485|doi:10.1021/acs.jmedchem.6b01881
CCDC 1516757: Experimental Crystal Structure Determination
Related Article: Bernd Kuhn, Michal Tichý, Lingle Wang, Shaughnessy Robinson, Rainer E. Martin, Andreas Kuglstatter, Jörg Benz, Maude Giroud, Tanja Schirmeister, Robert Abel, François Diederich, and Jérôme Hert|2017|J.Med.Chem.|60|2485|doi:10.1021/acs.jmedchem.6b01881
CCDC 1516756: Experimental Crystal Structure Determination
Related Article: Bernd Kuhn, Michal Tichý, Lingle Wang, Shaughnessy Robinson, Rainer E. Martin, Andreas Kuglstatter, Jörg Benz, Maude Giroud, Tanja Schirmeister, Robert Abel, François Diederich, and Jérôme Hert|2017|J.Med.Chem.|60|2485|doi:10.1021/acs.jmedchem.6b01881
CCDC 1516758: Experimental Crystal Structure Determination
Related Article: Bernd Kuhn, Michal Tichý, Lingle Wang, Shaughnessy Robinson, Rainer E. Martin, Andreas Kuglstatter, Jörg Benz, Maude Giroud, Tanja Schirmeister, Robert Abel, François Diederich, and Jérôme Hert|2017|J.Med.Chem.|60|2485|doi:10.1021/acs.jmedchem.6b01881