ETD

• AEA uptake
• allosteric modulation
• CB1R
• CB2R
• endocannabinoid system

The endocannabinoid system (ECS) is a ubiquitous neuromodulator system with wide-ranging actions, consisting on cannabinoid receptors (CB1R and CB2R), their endogenous ligands (endocannabinoids, EC) and the enzymes for EC synthesis and degradation. Since the discovery of allosteric binding site(s) on the CBRs, medicinal chem- istry research has been focusing on the development of different classes of allosteric modulators as they might offer a novel therapeutic approach with minimized side-effects. Moreover, EC degradation and membrane transporter inhibitors have been developed as they constitute an alternative therapeutic ap- proach to raise the levels of the EC preserving the beneficial effects derived from the direct activation of CBRs.
Based on the above reported, my PhD thesis can be divided in two main topics:
1. Design, synthesis and pharmacological evaluation of new classes of CBRs allosteric modulators:
2. Design, synthesis and pharmacological evaluation of 2-oxo-1,2-dihydro- pyridine-3-carboxamide derivatives as EC degradation and membrane transporter inhibitors.