0000000001305767

AUTHOR

Jérôme Hert

showing 7 related works from this author

Prospective Evaluation of Free Energy Calculations for the Prioritization of Cathepsin L Inhibitors.

2017

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 …

0301 basic medicinePrioritizationMolecular modelHalogenationStereochemistryCathepsin LComputational biology01 natural sciencesMolecular Docking SimulationProspective evaluationCathepsin L03 medical and health sciences0103 physical sciencesDrug DiscoveryHumansEnzyme InhibitorsBinding Sites010304 chemical physicsbiologyChemistryMolecular Docking Simulation030104 developmental biologyPyrimidinesDocking (molecular)Drug Designbiology.proteinMolecular MedicineThermodynamicsProtein BindingJournal of medicinal chemistry
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CCDC 1516759: Experimental Crystal Structure Determination

2017

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

Space GroupCrystallographyCrystal SystemCrystal Structure4-((13-benzodioxol-5-ylmethyl)(4-(trifluoromethyl)cyclohexyl)amino)-5-fluoropyrimidine-2-carbonitrileCell ParametersExperimental 3D Coordinates
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CCDC 1516760: Experimental Crystal Structure Determination

2017

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

Space GroupCrystallographyCrystal SystemCrystal Structure4-((13-benzodioxol-5-ylmethyl)(4-(cyclopropylmethoxy)phenyl)amino)-5-fluoropyrimidine-2-carbonitrileCell ParametersExperimental 3D Coordinates
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CCDC 1516761: Experimental Crystal Structure Determination

2017

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

Space GroupCrystallographyCrystal SystemCrystal StructureCell Parameters4-((13-benzodioxol-5-ylmethyl)(2-(2-methyl-4-oxo-6789-tetrahydro-4H-pyrido[12-a]pyrimidin-3-yl)ethyl)amino)-5-fluoropyrimidine-2-carbonitrileExperimental 3D Coordinates
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CCDC 1516757: Experimental Crystal Structure Determination

2017

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

Space GroupCrystallography4-((13-benzodioxol-5-ylmethyl)(1-methylcyclopropyl)amino)-5-fluoropyrimidine-2-carbonitrileCrystal SystemCrystal StructureCell ParametersExperimental 3D Coordinates
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CCDC 1516756: Experimental Crystal Structure Determination

2017

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

Space GroupCrystallography4-((13-benzodioxol-5-ylmethyl)(2-(pyridin-2-yl)ethyl)amino)-5-fluoropyrimidine-2-carbonitrileCrystal SystemCrystal StructureCell ParametersExperimental 3D Coordinates
researchProduct

CCDC 1516758: Experimental Crystal Structure Determination

2017

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

Space GroupCrystallography4-((13-benzodioxol-5-ylmethyl)(4-fluorophenyl)amino)-5-fluoropyrimidine-2-carbonitrileCrystal SystemCrystal StructureCell ParametersExperimental 3D Coordinates
researchProduct