From SAR Diagnostics to Compound Design: Development Chronology of the Compound Optimization Monitor (COMO) Method.

In medicinal chemistry, compound optimization largely depends on chemical knowledge, experience, and intuition, and progress in hit-to-lead and lead optimization projects is difficult to estimate. Accordingly, approaches are sought after that aid in assessing the odds of success with an optimization project and making decisions whether to continue or discontinue work on an analog series at a given stage. However, currently there are only very few approaches available that are capable of providing decision support. We introduce a computational methodology designed to combine the assessment of chemical saturation of analog series and structure-activity relationship (SAR) progression. The current endpoint of these development efforts, the compound optimization monitor (COMO), further extends lead optimization diagnostics to compound design and activity prediction. Hence, COMO plays dual role in supporting lead optimization campaigns.