Keynote review: Medicinal chemistry strategies to CB1 cannabinoid receptor antagonists

The proven clinical efficacy of the CB1 cannabinoid receptor antagonist rimonabant in both obesity and smoking cessation and its therapeutic potential in other disorders has given a tremendous impetus to the discovery of novel CB1 antagonists. The number of disclosed patents wherein novel chemical entities having CB1 antagonistic or inverse agonistic properties have been claimed has exploded. Besides novel compound classes that were identified in screening, rational medicinal chemistry approaches such as conformational constraint and scaffold hopping have been successfully applied. CB1 receptor modelling has provided insight into crucial receptor-ligand interaction points thereby leading to a general CB1 inverse agonist pharmacophore model.