2 research outputs found
Direct Access to Tetrahydro[1,2]diazepinones from α,β-Epoxy‑<i>N</i>‑aziridinylimines via Anionic Rearrangement
A novel one-step synthetic approach to tetrahydro[1,2]diazepinones via base-promoted rearrangement of α,β-epoxy-<i>N</i>-aziridinylimines, derived from α,β-epoxyketones and <i>N</i>-aminoaziridines, has been developed
Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA<sub>2</sub>)
Lp-PLA<sub>2</sub> has been explored as a target for a number of
inflammation associated diseases, including cardiovascular disease
and dementia. This article describes the discovery of a new fragment
derived chemotype that interacts with the active site of Lp-PLA<sub>2</sub>. The starting fragment hit was discovered through an X-ray
fragment screen and showed no activity in the bioassay (IC<sub>50</sub> > 1 mM). The fragment hit was optimized using a variety of structure-based
drug design techniques, including virtual screening, fragment merging,
and improvement of shape complementarity. A novel series of Lp-PLA<sub>2</sub> inhibitors was generated with low lipophilicity and a promising
pharmacokinetic profile