Lead Optimization and Compound Profiling

ACD/Labs' structure design solution offers a tool to synthetic/medicinal chemists to meet the challenges of property-based lead optimization. When the chemists' own portfolio of routine modifications to improve solubility, absorption, or penetration across the blood brain barrier fail, the software offers the capability to explore new ideas.

  • Incorporate appropriate physicochemical and ADME-Tox properties early in your lead optimization process
  • Test structure modification ideas prior to synthesis of new analogs
  • Prioritize synthetic modifications based on full and reliable physicochemical and ADME-Tox profiles

Optimize a structure for desired properties

The structure design solution uses the chemists knowledge of project objectives to select one or more sites of modification on a molecule, and define a desired property profile based on physicochemical, ADMÈ and toxicity parameters. Using this information, the software refines the customizable fragment database to substituents expected to meet property criteria. Analogs are generated automatically and can be reviewed and analyzed to select the best compounds with a balanced property profile.

Optimize structures for:

  • Lipophilicity (logP)
  • Ionization (pKa)
  • Number of hydrogen bond donors/acceptors
  • Molecular weight
  • Aqueous solubility
  • Central nervous system penetration
  • Human intestinal absorption

Review and Analyze resulting analogs

Review and Analyze resulting analogs
Click each image to zoom

The powerful spreadsheet workspace provides tools to help analyse, filter, sort and rank hundreds of analogs so that synthetic efforts can be focused on the best compounds. Property information for the generated analogs can be customized to meet the desired degree of detail. The Percepta profilers (ACD/PhysChem Profiler and ACD/Drug Profiler) provide full calculated property data for various endpoints. Plugging individual prediction modules into the structure design engine offers calculation protocols, the ability to train select models with experimental data and greater level of detail.

This solution is built upon experience and understanding of the synthetic chemistry workflow, and almost two decades of expertise in prediction of physicochemical and ADME-Tox properties.

Learn more about ACD/Structure Design Engine.