An unprecedented amount of parallel synthesis information was accumulated within Pfizer over the past 12 years. This information was captured by an informatics tool known as PGVL (Pfizer Global Virtual Library). PGVL was used for many aspects of drug discovery including automated reactant mining and reaction product formation to build a synthetically feasible virtual compound collection. In this report, PGVL is discussed in detail. The chemistry information within PGVL has been used to extract synthesis and design information using an intuitive desktop Graphic User Interface, PGVL Hub. Several real-case examples of PGVL are also presented.
PGVL Hub is an integrated molecular design desktop tool that has been developed and globally deployed throughout Pfizer discovery research units to streamline the design and synthesis of combinatorial libraries and singleton compounds. This tool supports various workflows for design of singletons, combinatorial libraries, and Markush exemplification. It also leverages the proprietary PGVL virtual space (which contains 10(14) molecules spanned by experimentally derived synthesis protocols and suitable reactants) for lead idea generation, lead hopping, and library design. There had been an intense focus on ease of use, good performance and robustness, and synergy with existing desktop tools such as ISIS/Draw and SpotFire. In this chapter we describe the three-tier enterprise software architecture, key data structures that enable a wide variety of design scenarios and workflows, major technical challenges encountered and solved, and lessons learned during its development and deployment throughout its production cycles. In addition, PGVL Hub represents an extendable and enabling platform to support future innovations in library and singleton compound design while being a proven channel to deliver those innovations to medicinal chemists on a global scale.
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