SynthI

SynthI interprets and unifies retrosynthetically generated fragments and reagent-derived fragments (synthons) to enable de novo, synthetically accessible library design in medicinal chemistry.

Key Features:

• Integration of Chemical Spaces: Merges retrosynthetically generated fragments and real-world reagents into a unified synthons space.
• Definition and Utilization of Synthons: Represents synthons as chemical fragments with valid valences and special labels indicating the position and nature of reactive centers, derived from compound breakup using 38 retrosynthetic rules or from real reagents by leaving-group withdrawal or transformation.
• Synthetically Accessible Library Design: Enables design of compound libraries with consideration of practical synthetic accessibility using available building blocks.
• Analog Generation and Reagent Analysis: Supports analog generation and detailed analysis of reagents (building blocks) for structure variation and selection.

Scientific Applications:

• De novo library design for drug discovery: Design and optimization of compound libraries for drug discovery in medicinal chemistry.
• Exploration of chemical space with synthetic feasibility: Systematic exploration of chemical spaces while retaining practical synthesis considerations.
• Analog generation and lead optimization: Generation of structural analogs to support identification and optimization of novel therapeutic candidates.

Methodology:

SynthI either breaks reference compounds using 38 retrosynthetic rules or converts real reagents into synthons via leaving-group withdrawal or transformation; synthons are represented with valid valences and labeled reactive centers and are merged into a unified synthons space.