SynthI: A New Open-Source Tool for Synthon-Based Library Design.

Area of Science:

• Chemoinformatics
• Medicinal Chemistry
• Computational Chemistry

Background:

• Existing de novo library design tools often lack a direct link to available reagents, making them theoretical.
• This disconnect hinders the practical synthesis of designed chemical libraries.

Purpose of the Study:

• Introduce Synthons Interpreter (SynthI), an open-source toolkit for de novo library design.
• To merge the chemical spaces of retrosynthetically generated fragments and available reagents into a unified synthons space.

Main Methods:

• SynthI defines synthons as fragments with valid valences and reactive center labels.
• Synthons are derived from reference compounds using 38 retrosynthetic rules or from real reagents after modification.
• The toolkit integrates fragment and reagent chemical spaces.

Main Results:

• SynthI enables the design of synthetically accessible chemical libraries.
• Facilitates the generation of analogs for drug discovery.
• Aids in the analysis of building blocks within medicinal chemistry.

Conclusions:

• Synthons Interpreter (SynthI) provides a practical approach to de novo library design.
• The toolkit enhances the link between computational design and synthetic feasibility.
• SynthI is a valuable resource for medicinal chemists and chemoinformaticians.