Recent advances in the trifluoromethylation methodology and new CF3-containing drugs

• Published in: Journal of fluorine chemistry Vol. 167; pp. 37 - 54
• Main Authors: Zhu, Wei, Wang, Jiang, Wang, Shuni, Gu, Zhanni, Aceña, José Luis, Izawa, Kunisuke, Liu, Hong, Soloshonok, Vadim A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-11-2014
• Subjects: Biological activity; Fluorine-containing drugs; Methodology; Pharmaceuticals; Trifluoromethylation; Trifluoromethylation; Methodology; Fluorine-containing drugs; Biological activity; Pharmaceuticals
• ISSN: 0022-1139; 1873-3328
• DOI: 10.1016/j.jfluchem.2014.06.026

•Assessment of current methods for the synthesis of CF3-containing molecules.•Description of five trifluoromethylated new drug candidates.•Evaluation of the synthetic routes developed for each compound.•More advanced protocols for trifluoromethylation reactions are still eagerly needed.
This review provides a brief assessment of the methodological field of trifluoromethylation and its possible impact on the development of new CF3-containing pharmaceuticals. Structural aspects of five new drug-candidates, [tafenoquine (aromatic CF3), roniciclib (heteroaromatic CF3), BAY-38-7271 (aliphatic CF3), sonidegib (OCF3) and navitoclax (S-CF3)] currently under the development in phase II and III clinical studies, and their biological properties, therapeutic area and synthesis are critically discussed.