Mapping under-represented chalcone chemical space with an open-source Virtual Chalcone Library (VCL)
- 1Materials Innovation Factory, University of Liverpool, 51 Oxford Street, Liverpool, UK
Abstract
Chalcones are highly versatile privileged scaffolds, yet substantial regions of their synthetically accessible chemical space remain under-explored. Herein, we report an open-source Virtual Chalcone Library (VCL) comprising 489,475 unique structures generated from commercially available aromatic ketones and aldehydes using the freely available DataWarrior platform. Comparison of the VCL with a curated dataset of 8,886 literature chalcones revealed structural bias towards a small number of pharmacophore motifs, while highlighting under-represented regions of chemical space. Benzofuran-containing chalcones emerged as a prominent example and were selected as a case study for prospective exploration. Physicochemical filtering for favourable medicinal chemistry properties reduced this region to 1,181 candidates, from which diversity analysis identified 30 representative structures. Six novel chalcones were selected and successfully prepared, establishing two “synthetic outposts” in under-represented chemical space. A series of “deep-space” virtual chalcones (DS1-DS9) were identified with DS6 synthesised from commercially available starting materials. These syntheses provide experimental validation of the data-driven, VCL-guided workflow. The VCL is openly available as a community resource, accompanied by tutorials for its implementation and analysis in DataWarrior. This study establishes a framework for identifying, prioritising and experimentally accessing under-represented regions of chalcone chemical space.
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BibTeX
@misc{ciupa2026mapping,
title = {{Mapping under-represented chalcone chemical space with an open-source Virtual Chalcone Library (VCL)}},
author = {Alexander Ciupa},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009717/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009717/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Mapping under-represented chalcone chemical space with an open-source Virtual Chalcone Library (VCL)
AU - Alexander Ciupa
PY - 2026
DA - 2026/10/01
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009717/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009717/v1
AB - Chalcones are highly versatile privileged scaffolds, yet substantial regions of their synthetically accessible chemical space remain under-explored. Herein, we report an open-source Virtual Chalcone Library (VCL) comprising 489,475 unique structures generated from commercially available aromatic ketones and aldehydes using the freely available DataWarrior platform. Comparison of the VCL with a curated dataset of 8,886 literature chalcones revealed structural bias towards a small number of pharmacophore motifs, while highlighting under-represented regions of chemical space. Benzofuran-containing chalcones emerged as a prominent example and were selected as a case study for prospective exploration. Physicochemical filtering for favourable medicinal chemistry properties reduced this region to 1,181 candidates, from which diversity analysis identified 30 representative structures. Six novel chalcones were selected and successfully prepared, establishing two “synthetic outposts” in under-represented chemical space. A series of “deep-space” virtual chalcones (DS1-DS9) were identified with DS6 synthesised from commercially available starting materials. These syntheses provide experimental validation of the data-driven, VCL-guided workflow. The VCL is openly available as a community resource, accompanied by tutorials for its implementation and analysis in DataWarrior. This study establishes a framework for identifying, prioritising and experimentally accessing under-represented regions of chalcone chemical space.
ER -