Ligand-free Pd-catalyzed C–N cross-coupling/cyclization strategy: An unprecedented access to 1-thienyl pyrroloquinoxalines for the new approach towards apoptosis

•First synthesis of 1-thienyl pyrroloquinoxalines has been achieved.•A ligand-free Pd-catalyzed strategy has been used for this purpose.•These compounds showed PDE4 inhibitory properties in vitro.•These compounds were also screened in zebrafish embryos.

The link between PDE4 and apoptosis prompted us to design and synthesize for the first time a series of novel 1-thienyl pyrroloquinoxalines as potential PDE4 inhibitors/apoptotic agents. A ligand-free Pd-catalyzed C–N cross-coupling/cyclization strategy has been developed for the rapid and milder access to this class of compounds some of which showed interesting pharmacological properties when tested in vitro and in zebrafish embryos.

Graphical abstractNovel 1-thienyl pyrroloquinoxaline based PDE4 inhibitors have been identified as new agents for apoptosis.Figure optionsDownload full-size imageDownload as PowerPoint slide