Discovery of tetrahydro- ß-carboline derivatives as a new class of phosphodiesterase 4 inhibitors

In this study, two novel series of tetrahydro- β-carbolines were designed by combining the pharmacophoric features of both tadalafil and piclamilast. Twenty-two compounds were synthesized and assessed for Phosphodiesterase 4 inhibition, four of them showed superior activity to the reference compound IBMX. Docking studies showed that the prepare d compounds interact with the crucial Gln443 with variable interactions with the hydrophobic pocket Q2. This is the first report of tetrahydro-β-carbolines as a scaffold for Phosphodiesterase 4 inhibition. Currently, further optimization of the substituents is carried out to fine-tune the hydrophob ic interactions and enhance the potency of this novel series of inhibitors.Graphical abstract
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research