Ligand-Based Fluorine NMR Screening: Principles and Applications in Drug Discovery Projects
- 8 October 2018
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 62 (5), 2218-2244
- https://doi.org/10.1021/acs.jmedchem.8b01210
Abstract
Ligand-based fluorine NMR screening has gained popularity in drug discovery projects during the past decade and has become a powerful methodology to produce high quality hits. Its high sensitivity to protein binding makes it particularly suitable for fragment screening allowing detection and binding strength measurement of very weak affinity ligands. The screening can be performed in direct or competition format and its versatility allows application to complex biological and chemical systems. As the potential of the methodology has now been recognized and successfully demonstrated in several relevant medicinal chemistry projects, is now an appropriate time to report the learned lessons and point the way to the future. In this perspective the principles of the methodology along with several applications to pharmaceutical projects are presented.Keywords
This publication has 116 references indexed in Scilit:
- A New Reagent for Direct DifluoromethylationJournal of the American Chemical Society, 2012
- Fluorine in health care: Organofluorine containing blockbuster drugsJournal of Fluorine Chemistry, 2010
- 19F NMR chemical shift prediction with fluorine fingerprint descriptorJournal of Fluorine Chemistry, 2010
- 19F NMR applications in chemical biologyJournal of Fluorine Chemistry, 2009
- Use of fluorinated functionality in enzyme inhibitor development: Mechanistic and analytical advantagesJournal of Fluorine Chemistry, 2008
- Non-carbohydrate Inhibitors of the Lectin DC-SIGNJournal of the American Chemical Society, 2007
- Fluorine in medicinal chemistry: Recent therapeutic applications of fluorinated small moleculesJournal of Fluorine Chemistry, 2006
- Fluorine in medicinal chemistry: A review of anti-cancer agentsJournal of Fluorine Chemistry, 2006
- Fluorine chemistry at the millenniumJournal of Fluorine Chemistry, 2005
- 2D experiments for the characterization of fluorinated polymers: pulsed-field gradients 1H–19F hetero-COSY and its selective versionJournal of Fluorine Chemistry, 2000