Ladderane as a Saturated Bioisostere of ortho-Benzene
Previously, we proposed a hypothesis that ladderanes could mimic ortho-benzene in bioactive compounds. In this work, we have proven this hypothesis experimentally. In particular, 2,3-disubstituted ladderanes were efficiently synthesized and extensively characterized. These cores were then incorporated into six bioactive compounds instead of the benzene ring. The corresponding patent-free ladderane derivatives of Thalidomide and Oxatomide showed improved physicochemical profiles and similar biological activities compared to those of the original drugs. These results confirm that ladderanes can act as saturated bioisosteres of ortho-benzenes.
Authors
- Viktoriia Kosach (ORCID: https://orcid.org/0000-0002-8214-9604)
- Oleksandr P. Datsenko
- Pavel K. Mykhailiuk (ORCID: https://orcid.org/0000-0003-1821-9011)
- Oleh V. Shablykin (ORCID: https://orcid.org/0000-0001-6810-9860)
- Iryna Pishel (ORCID: https://orcid.org/0000-0002-5267-6817)
- Petro Borysko (ORCID: https://orcid.org/0000-0002-5840-5233)
- V. O. Stadnichenko (ORCID: https://orcid.org/0009-0006-8083-126X)
- Anna Beshtynarska
- Liana Dmytrovska
- Юрій Млинченко
- Nataliia Barchenko
Institutions
- Taras Shevchenko National University of Kyiv (UA)
- Institute of Bioorganic Chemistry and Petrochemistry V.P. Kukhar (UA)
- Enamine (Ukraine) (UA)
Publication Details
- Journal
- ChemRxiv
- Published
- 2026-10-29
- DOI
- https://doi.org/10.26434/chemrxiv.15011261/v1
- Primary Topic
- Synthesis and biological activity
- Type
- preprint