Identification of dihydroquinolizinone derivatives with nitrogen heterocycle moieties as new anti-HBV agents

In this study, we designed and synthesized a series of DHQs incorporating nitrogen heterocycle moieties. Almost all of these compounds exhibited potent inhibition activity against HBsAg, with IC50 values at the nanomolar level. Impressively, the compound (S)-2a (10 μM) demonstrated a comparatively reduced impact on the neurite outgrowth of HT22 cells and isolated mouse DRG neurons in comparison to RG7834, thereby indicating a decrease in neurotoxicity. Furthermore, (S)-2a exhibited higher drug exposures than RG7834. The potent anti-HBV activity, reduced neurotoxicity, and favorable pharmacokinetic profiles underscore its promising potential as a lead compound for future anti-HBV drug discovery.PMID:38458109 | DOI:10.1016/j.ejmech.2024.116280

Source: European Journal of Medicinal Chemistry - March 8, 2024 Category: Chemistry Authors: Huijuan Song Shangze Yang Shuo Wu Xiaoyu Qin Ya Wang Xican Ma Jiaqi Gong Meng Wei Apeng Wang Mengyuan Wang Kun Lan Juan Guo Mingliang Liu Xingjuan Chen Yuhuan Li Kai Lv Source Type: research