Numerous analyses have been published on the importance of high quality screening collections, focusing on factors such as lead-like properties, 3D shape, diversity, novelty and privileged substructures. One pragmatic way to achieve this is with improved access to novel, high quality building blocks, but the design principles that should govern strategic acquisitions and custom synthesis of such reagents has been rather overlooked in the literature. Reagents that can capture medicinal chemistry learning and are designed to impart favorable physical properties when used to synthesize project compounds can accelerate drug discovery programs and enhance the quality of compound collections. This is particularly true when attempting to incorporate saturation and 3D shape, as the synthetic difficulties involved with the resulting chirality can be prohibitive. In this presentation we will present our strategy to address this with custom synthesis to harness the learning from our internal programs and external literature. >60k compounds in the AstraZeneca (AZ) compound collection have incorporated these reagents, resulting in numerous project impact examples and three candidate drugs. This presentation will discuss the methods we have used with examples, and the properties of the resulting reagent set vs. ACD. We will discuss what constitutes a �popular reagent� in medicinal chemistry, by analyzing the contribution of different reagent types to the AZ compound collection and the usage of reagents in the AZ electronic lab notebook. We shall also present the structures of real project examples to exemplify how these reagents have been used by our medicinal chemistry teams.

Design of novel reagent sets to enhance drug discovery

247th National Meeting (2014)

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