New Trends in Medicinal Chemistry Approaches to Antiobesity Therapy

Abstract

The prevalences of overweightedness and obesity are increasing globally at frightening rates, driven by social and economic changes. Furthermore, obesity is associated with the pathogeneses of major diseases, particularly diabetes and cardiovascular diseases. However, no satisfactorily safe, effective obesity drugs are commercially available at the present time. Only two drugs have been approved in the United States for the long-term treatment of obesity, sibutramine and orlistat. However, these drugs are minimally effective and have significant side effects, which are likely inhibit their use. Therefore, there is a huge opportunity to make a significant impact on the lives of obese people through the discovery and development of additional pharmacotherapeutic options. In this review article, the authors focus on selected trends in medicinal chemistry and the approaches used to develop drugs for treating obesity.

An indoline-derived compound that markedly reduces mouse body weight

“…1 Efficacious and safe pharmacological treatments have yet to emerge. 2 The most successful anti-obesity drug treatments to date have resulted in only a modest 5-11% human body weight loss over 1 year, and all of these treatments except for orlistat (Xenical) have been withdrawn from the market owing to unwanted side effects. [3][4][5] Serendipitously, during toxicology testing of an indolinederived class of potential anticancer compounds (designed as prodrugs for release of a DNA alkylating agent in hypoxic tumor tissue), we discovered that female C3H/HeN mice shed 425% of their body weight over 3-4 weeks following a single intraperitoneal (i.p.)…”