Multicomponent Synthesis of Fluorine‐Containing Bioactive Compounds and Drugs

Multicomponent reactions are robust synthetic tools to assamble complex polyheterocycles and other interesting molecular architectures with potential application in medicinal chemistry, including their fluorine-containing analogues. Fluorine atoms placed strategically into bioactive molecules often enhance essential pharmacokinetic parameters like bioavailability, lipophilicity and metabolic resistance. Indeed, various marketed drugs contain fluorine atoms in their structures.

It is well known that fluorine atoms placed strategically into bioactive molecules often enhance essential pharmacokinetic parameters like bioavailability, lipophilicity, and metabolic resistance. In the same way, a relatively broad spectrum of marketed drugs contains one or more fluorine atoms in their structures, usually in the form of fluorine-, difluoromethyl-, trifluoromethyl-, or perfluoroalkyl aromatic moieties, being essential parts of their corresponding pharmacophores. Besides, multicomponent reactions (MCR) are highly convergent one-pot processes in which three or more smartly substituted/functionalized reagents are combined simultaneously, sequentially or consecutively, in the same reactor to assemble complex products (including polyheterocycles) containing most or all atoms from the reagents. Thus, the scope of the present review is to discuss selected MCR-based works since 2009 for the synthesis of bioactive compounds and drugs that contain at least one fluorine atom in their structures, as well as relevant results from in silico, in vitro, and/or in vivo studies against a variety of important target biomolecules, highlighting the role of fluorine-containing moieties.

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