CB1 cannabinoid receptor antagonists

Interest in the pharmacology of cannabinoids (CBs) has rapidly increased after the cloning of cannabinoid receptors and the discovery of their endogenous ligands (endocannabinoids) in the early 1990's [1,2]. In this context, the discovery of the first cannabinoid antagonist, rimonabant (SR141716, 1), in 1994, has provided researchers with an important tool for determining the physiological role of the endocannabinoid system. The interest in CB1 antagonists further increased when the first clinical results on the use of rimonabant for the treatment of obesity and related metabolic disorders were reported in 2001 [3]. Considering the important impact of obesity on public health, the dramatic increase of its worldwide prevalence and the lack of highly efficient and well-tolerated drugs to cure it, it is no surprise that CB1 antagonists are currently the subject of intense research in both industrial and academic groups. Advances in cannabinoid ligands [4] and CB1 antagonists [5,6] have been reviewed recently. In this chapter, we will focus on important results published in the field of the medicinal chemistry of CB1 antagonists since the publication of the review by Xiang and Lee [7], with a special emphasis on very recently reported new structures and new potential clinical applications. © 2005 Elsevier Inc. All rights reserved.