Design and synthesis of novel xanthene derivatives

Xanthenes are a special class of oxygen-incorporating tricyclic compounds. Structurally related to xanthones, the presence of different substituents in position 9 presents a large impact on their physical and chemical properties, as well as their biological applications. Xanthene-9-carboxylic acid, 9-hydroxyxanthene (xanthydrol) and their respective derivatives have been reported to exhibit remarkable biological activities, namely neuroprotection, antidiabetic, cytotoxic, and antibacterial.

Herein, we report the design of a virtual library of 300 compounds whose pharmacokinetic properties were assessed through computational tools. Synthesis strategies to obtain such drug-like xanthene derivatives - amide coupling, reductive amination, aromatic halogenation and Suzuki coupling - are described. Azaxanthenes and thioxanthenes, important xanthene bioisosters, are also considered for their capacity to establish different biologic interactions for their influence pharmacokinetic properties. Future studies will include the investigation of their potential as bioactive compounds.