Basicity and Lipophilicity of <i>gem</i> ‐Difluorinated Saturated Bicyclic Amines: Advanced Building Blocks for Drug Discovery
The impact of gem ‐difluorination on the physicochemical properties of bicyclic saturated amines with 6–8 atoms in the largest ring is studied. The fluorination effect on the acidity of protonated species (p K a ) aligns with predictions based on the inductive effect of the electron‐deficient substituent. In contrast, lipophilicity (Log P ) could either increase or decrease due to gem ‐difluorination. The observed effect depends on the number of vicinal CH bonds relative to the fluorine atoms, but it is also influenced by their relative spatial orientation and the structure of the bicyclic core itself.
Authors
- Serhii Holovach (ORCID: https://orcid.org/0009-0004-2214-1880)
- Oleksandr S. Liashuk (ORCID: https://orcid.org/0000-0002-2677-435X)
- Oleksandr O. Grygorenko (ORCID: https://orcid.org/0000-0002-6036-5859)
- Andrey А. Filatov (ORCID: https://orcid.org/0000-0001-7050-8131)
- Kostiantyn P. Melnykov (ORCID: https://orcid.org/0009-0003-6522-681X)
- Petro Borysko (ORCID: https://orcid.org/0000-0002-5840-5233)
- Dmytro Lesyk (ORCID: https://orcid.org/0009-0001-3391-5165)
- Yuliia Holota (ORCID: https://orcid.org/0009-0009-2329-7111)
- B. L. Moroz
- Daniil Skrypnik
- Yaroslav Lesyk
Institutions
- Taras Shevchenko National University of Kyiv (UA)
- Institute of Bioorganic Chemistry and Petrochemistry V.P. Kukhar (UA)
- Institute of Organic Chemistry (UA)
- Enamine (Ukraine) (UA)
Publication Details
- Journal
- European Journal of Organic Chemistry
- Published
- 2025-09-09
- DOI
- https://doi.org/10.1002/ejoc.202500728
- Citations
- 3
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 2.37
Funders
- Ministry of Education and Science of Ukraine
- Enamine