Enamine Ltd., Chervonotkatska Street 78, Kyїv, 02094, Ukraine.
Taras Shevchenko National University of Kyїv, Volodymyrska Street 60, Kyїv, 01601, Ukraine.
ChemMedChem. 2022 Nov 4;17(21):e202200365. doi: 10.1002/cmdc.202200365. Epub 2022 Oct 5.
The review covers various aspects of fluorinated cycloalkyl (C -C ) building blocks for drug discovery, including their synthesis, key physicochemical properties, and biological and medicinal applications of their derivatives. The discussed synthetic methods include classical nucleophilic fluorinations of various substrates, the addition of fluorine and another heteroatom to double bonds, cycloadditions and other transformations of fluorine-containing substrates, as well as some newer reactions like fluorination of non-activated and remotely activated C-H bonds, decarboxylative and deborylative fluorinations, etc. The known data on the effect of introducing the fluorinated cycloalkyl groups on the compound's key in vitro parameters (such as acidity/basicity, lipophilicity, conformational behavior, and short contact capabilities) are surveyed. Finally, applications of fluorinated cycloalkyl building block derivatives in the design of biologically active compounds (including marketed drugs Maraviroc, Ivosidenib, and Sitafloxacin) are covered, with a focus on the fluorination impact.
该综述涵盖了用于药物发现的氟化环烷基（C-C）构建块的各个方面，包括它们的合成、关键物理化学性质以及它们的衍生物的生物和医学应用。讨论的合成方法包括各种底物的经典亲核氟化、氟和另一个杂原子向双键的加成、含氟底物的环加成和其他转化，以及一些较新的反应，如非活化和远程活化 C-H 键的氟化、脱羧和脱硼氟化等。调查了引入氟化环烷基对化合物关键体外参数（如酸度/碱度、亲脂性、构象行为和短程接触能力）的影响的已知数据。最后，涵盖了氟化环烷基构建块衍生物在设计生物活性化合物（包括上市药物马拉维若、ivosidenib 和司他氟沙星）中的应用，重点介绍了氟化的影响。
