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Mapping the Efficiency and Physicochemical Trajectories of Successful Optimizations.

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Young RJ,Leeson PD

doi

10.1021/acs.jmedchem.8b00180

subject

Has Abstract

pub_date

2018-08-09 00:00:00

pages

6421-6467

issue

15

eissn

0022-2623

issn

1520-4804

journal_volume

61

pub_type

杂志文章,评审

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