DIY Virtual Chemical Libraries - Novel Starting Points for Drug Discovery

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Chemical Synthesis

Background:

• * Drug discovery pipelines increasingly utilize virtual libraries due to advancements in *in silico* technologies like library enumeration and synthetic feasibility prediction.
• * External virtual libraries offer vast compound pools but often incur long delivery times and high costs.
• * There is a need for accessible, cost-effective chemical starting points for drug discovery.

Purpose of the Study:

• * To develop and characterize a Do-It-Yourself (DIY) combinatorial chemistry library.
• * To assess the utility of this DIY library for various drug discovery applications.
• * To present an internally generated library as a viable alternative to external virtual catalogs.

Main Methods:

• * Construction of a combinatorial chemistry library using 1000 low-cost building blocks.
• * Application of robust, frequently used reactions in medicinal chemistry.
• * Generation of over 14 million novel chemical products.
• * Profiling of physicochemical properties and structural diversity.
• * Creation of focused libraries for specific drug discovery needs.

Main Results:

• * A DIY combinatorial chemistry library exceeding 14 million novel compounds was successfully built.
• * The library utilizes low-cost building blocks and robust synthetic reactions.
• * Extensive profiling confirmed the library's physicochemical properties and structural diversity.
• * Focused libraries were generated, demonstrating applicability in drug discovery.

Conclusions:

• * Internally built DIY chemical libraries provide a cost-effective and rapid source of potential drug starting points.
• * This approach complements and offers a viable alternative to external virtual compound catalogs.
• * DIY libraries enhance accessibility to diverse chemical matter for drug discovery efforts.