Building a Diverse and Experimentally-Curated Fragment Library

Fragment libraries are commonly assembled by Rule of 3 filtering followed by manual curation. However, the robust experimental data that ensures the proper physicochemical attributes needed for high-concentration screening is often lacking and replaced instead by in silico calculations of uncertain predictive value. A fragment collection with experimentally-determined aqueous solubility will address a major source of false positives and attrition in fragment screening libraries: Aggregation, Stability, and Solubility. 1H NMR spectral data in aqueous buffer will further enable practitioners to rapidly build fragment pools and initiate screening.