Combining computational lead optimization diagnostics with analog design and computational approaches for assessing optimization efforts are discussed and the compound optimization monitor is introduced.
Approaches for compound potency prediction are described and a new analog design algorithm is introduced. Calculation protocols are detailed.
The study rationale is explained. Compound optimization monitor diagnostics are combined with a thoroughly evaluated approach for compound design and candidate prioritization. The diagnostic scoring scheme is further extended.
Compound optimization is a central task in medicinal chemistry, which has many potential pitfalls. Computational approaches that help to better understand and guide chemical optimization efforts are highly desirable, but only a few are currently available. We have aimed to develop a computational methodology that combines, for the first time, the evaluation of progress in chemical optimization with the design of new candidate compounds.