High quality HTS hits are important for drug discovery programs to expedite the timelines associated with medchem optimizations and improve overall success rates in the clinic. To provide such high quality HTS hits, original compound libraries play an important role in HTS strategy. In addition, a compound library with enhanced CNS drug-likeness (good brain penetrability and good oral availability) would improve the productivity of drug discovery programs in the Neuroscience area. Against this background, we have been constructing a CNS-focused compound library by: -Innovative design to improve the probability of the compounds reaching the CNS. -Extensive in vitro, in vivo and physicochemical characterization of library members to eliminate structures with inherent liabilities. -Continuous addition of newly-designed innovative scaffold structures. In this poster, we describe our strategy for constructing a CNS-focused compound library utilizing the combination of a computational scoring system and in vitro/in vivo DMPK data. In addition, we also describe how we gathered our original scaffold collection to emphasize structural novelty in the library.

Development and construction of an original compound library for CNS drug discovery: Combining computational and wet data to enhance CNS drug-likeness

255th National Meeting (2018)

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