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Review
. 2025 Jul 18;30(14):3009.
doi: 10.3390/molecules30143009.

The Role of Trifluoromethyl and Trifluoromethoxy Groups in Medicinal Chemistry: Implications for Drug Design

Manuel Novás  1 , Maria J Matos  1
Affiliations
Review

The Role of Trifluoromethyl and Trifluoromethoxy Groups in Medicinal Chemistry: Implications for Drug Design

Manuel Novás et al. Molecules. .

Abstract

One of the key strategies in drug design involves modifying molecular scaffolds with specific chemical groups, or side chains, to enhance biological and physicochemical properties. These modifications can strengthen interactions with biological targets or improve pharmacokinetic and physicochemical characteristics, factors that are critical in transforming a compound into a viable drug candidate. In this overview, we focus on the presence of trifluoromethyl and trifluoromethoxy groups on different molecules, highlighting their relevance and impact in medicinal chemistry. The discussion and future perspectives in the field are based on a comprehensive review of current literature, with data sourced mainly from SciFinder and PubMed.

Keywords: drug design; medicinal chemistry; trifluoromethoxy group; trifluoromethyl group.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Chemical characteristics of the trifluoromethyl group. Electrostatic potential map in the range of −0.1 to 0.1 obtained using MolCalc®, where warm colors indicate higher and blue indicates lower electron density. Blue: positive; red: negative.
Figure 2
Figure 2
Chemical characteristics of the trifluoromethoxyl group. Electrostatic potential maps in the range of −0.1 to 0.1 obtained using MolCalc®, where warm colors indicate higher and blue indicates lower electron density. Blue: positive; red: negative.
Figure 3
Figure 3
Examples of drugs bearing trifluoromethyl groups (highlighted in green) and their therapeutic applications.
Figure 4
Figure 4
Examples of drugs bearing trifluoromethoxy groups (highlighted in pink) and their therapeutic applications.
See this image and copyright information in PMC

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