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Strategically Placed Trifluoromethyl Substituent in the Realm of Antitubercular Drug Design

[ Vol. 14 , Issue. 2 ]


Sidhartha S. Kar and Cinu A. Thomas*   Pages 114 - 123 ( 10 )


Background: Fluorinated substituents have played, and continue to play an important role in antitubercular drug design. Nonetheless, previous works have indicated that organofluorines like –F, CF3, -OCF3, and CHF2 etc have been used to modulate the pharmacodynamic and pharmacokinetic behaviour of antitubercular agents. Among the fluorinated groups, trifluoromethyl (-CF3) substituent is a very familiar pharmacophore used widely in antitubercular research.

Objective: This review assesses the development of selected trifluoromethyl group bearing antitubercular agents that are either in treatment or considered to be potential. The prime objective of the present investigation was to provide initial evidences for the hypothesis that addition of trifluoromethyl group to antiTB agents could improve their potency. We also aimed to contribute to a better understanding of the role of trifluoromethyl group on drug-likeness antitubercular activity.

Methods: In this review, we first brief out the possible effect of –CF3 substituent on pharmacodynamic and pharmacokinetic properties of drugs. Next, we turn to emphasize on the effect of trifluoromethyl substituent on different antitubercular scaffolds. Finally, we open the topic for the researchers to design potential antitubercular agents suitably substituted with fluorinated groups.

Results: This review suggests that the replacement of –CF3 group in heterocyclic as well as phenyl ring led to the improvement in pharmacodynamic and pharmacokinetic properties of the compounds. Hence it's not surprising to see –CF3 group emerging as an alternative electron withdrawing group instead of halogens in many promising antitubercular agents.

Conclusion: This unusual spectrum of advantage allied with its lipophilicity enhancing effect, made –CF3 group distinct from other substituents in modern antitubercular drug design. The present study provides conceptual advances to the understanding of the physicochemical properties of –CF3 group and its effect on antitubercular activity.


Trifluoromethyl group, antitubercular agents, structure-activity relationships, drug-likeness, pharmacodynamic, pharmacokinetic.


Department of Pharmaceutical Chemistry, Institute of Pharmacy & Technology, Cuttack-754202, Department of Pharmacy, Mahatma Gandhi University, Kottayam

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