“…In addition, the desadamantyl 1,2,4-triazole derivatives IV [21], V [22] and VI [23], are currently under clinical investigations as 11β-HSD1 inhibitors for the treatment of type 2 diabetes and obesity (Figure 1). According to experimental and molecular docking studies for the identification of chemical features of 11β-HSD1 inhibitors, a combination of an adamantane cage-and 1,2,4-triazole or other azole moieties could result in potent 11β-HSD1 inhibitors [15,16,[24][25][26][27][28][29]. In continuation with ongoing interest in the structural properties [30][31][32][33][34][35] and biological applications of adamantane-based derivatives [35][36][37][38][39], we report herein on the molecular structure insights, Hirshfeld surface analysis and pairwise interaction energies of three adamantane-linked 1,2,4-triazole N-Mannich bases, namely ethyl 4-[(3adamantan-1-yl)-4-ethyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)methyl]piperazine-1carboxylate (1), 5-(adamantan-1-yl)-4-ethyl-2-[(4-(pyridin-2-yl)piperazin-1-yl)methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (2) and 5-(adamantan-1-yl)-4-allyl-2-[(4-(pyridin-2yl)piperazin-1-yl)methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (3), which were proven to possess marked hypoglycemic activity [39].…”