DOI: 10.1021/acs.jmedchem.6c00627 ISSN: 0022-2623
Strategic Use of the Necessary Nitrogen Atom for Holistic Property-Based Drug Design
Lewis D. Pennington, Julia M. Clay, Sandrine M. Hell, Matthew J. Hesse, Elizabeth V. Jones, Rory C. McAtee, Theodore D. Michels, Alshaima’a M. QuniesAbstract
Property-based drug design has advanced considerably since its emergence following the publication of the rule-of-5 in 1997. We show in this perspective that the classical bioisosteric exchange of an aromatic methine group with a nitrogen atom has broad utility in the modern context of drug multiparameter optimization. We also demonstrate how the “necessary nitrogen atom” can be leveraged for holistic property-based drug design, and include a historical overview, key concepts, and real-world case studies.