The enzyme 11 beta-hydroxysteroid clehydrogenase type 1 (11 beta-HSD1) converts cortisone to the active glucocorticoid cortisol, thereby acting as a cellular switch to mediate glucocorticoid action in many tissues. Several studies have indicated that 11 beta-HSD1 plays a crucial role in the onset of type 2 diabetes and central obesity. As a consequence, selective inhibition of 11 beta-HSD1 in humans might become a new and promising approach for lowering blood glucose concentrations and for counteracting the accumulation of visceral fat and its related metabolic abnormalities in type 2 diabetes. In this study, we present the synthesis and the biological evaluation of ursan or oleanan type triterpenoids which may act as selective 11 beta-HSD1 inhibitors in liver as well as in peripheral tissues, like adipocytes and muscle cells. In order to rationalise the outcomes of the inhibition data, docking simulations of the ligands were performed on the experimentally determined structure of 11 beta-HSD1. Furthermore, we discuss the structural determinants that confer enzymatic specificity. From our investigation, valuable information has been obtained to design selective 11 beta-HSD1 blockers based on the oleanan and ursan scaffold. (c) 2008 Elsevier Ireland Ltd. All rights reserved.