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ID: ALA4190376

Journal: J Med Chem

Title: Mapping the Efficiency and Physicochemical Trajectories of Successful Optimizations.

Authors: Young RJ, Leeson PD.

Abstract: The practices and tactics employed in successful optimizations are examined, judged from the trajectories of ligand efficiency and property evolution. A wide range of targets is analyzed, encompassing a variety of hit finding methods (HTS, fragments, encoded library technology) and types of molecules, including those beyond the rule of five. The wider employment of efficiency metrics and lipophilicity control is evident in contemporary practice and the impact on quality demonstrable. What is clear is that while targets are different, successful molecules are almost invariably among the most efficient for their target, even at the extremes. Trajectory mapping, based on principles rather than rules, is useful in assessing quality and progress in optimizations while benchmarking against competitors and assessing property-dependent risks.

CiteXplore: 29620890

DOI: 10.1021/acs.jmedchem.8b00180