Design of low dose compounds has always been a primary focus of medicinal chemistry project teams. Until recently, this problem was simplified to independent optimization of parameters that impact the dose, such as potency or intrinsic clearance, without much regard to the tradeoffs among the different terms that determine the dose. It has become clear recently that the trends that improve one property (such as potency) often oppose the trends that improve another property (such as intrinsic clearance) of molecules. The independent optimization of parameters that impact the dose becomes of limited use in these scenarios and often causes ambiguity among project teams with some members focusing on one property while other members of the project team focusing on a different property. This presentation will focus on the rational optimization of compounds towards low dose compounds for Ctrough targets and highlight the tradeoffs among different terms that impact the dose projections. The presentation will highlight the currently available tools and their application in drug discovery projects and provide recommendations on how to enable them for project teams.

Is rational dose optimization a myth?

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.