Design and construction of a stereochemically diverse piperazine-based DNA-encoded chemical library

Bioorg Med Chem. 2021 Oct 15:48:116387. doi: 10.1016/j.bmc.2021.116387. Epub 2021 Sep 13.

Abstract

Here we report the successful construction of a novel, stereochemically diverse DNA-Encoded Chemical Library (DECL) by utilizing 24 enantiomerically pure trifunctional 2, 6- di-substituted piperazines as central cores. We introduce the concept of positional diversity by placing the DNA attachment at either of two possible sites on the piperazine scaffold. Using a wide range of building blocks, a diverse library of 77 million compounds was produced. Cheminformatic analysis demonstrates that this library occupies a wide swath of chemical space, and that the piperazine scaffolds confers different shape diversity compared to the commonly used triazine core.

Keywords: (sp3) rich compound collection; Encoded chemistry; Piperazines; Stereochemical diversity; Stereogenic compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Combinatorial Chemistry Techniques
  • DNA / drug effects*
  • Drug Design*
  • Molecular Structure
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Stereoisomerism

Substances

  • Piperazines
  • Small Molecule Libraries
  • DNA