Zhang, Xiangyu published the artcileDesign, synthesis and biological evaluation of novel benzofuran derivatives as potent LSD1 inhibitors, Synthetic Route of 73874-95-0, the main research area is cyanophenyl aminomethyl arylbenzofuran preparation; LSD1 cytochromep450 inhibition SAR antitumor cytotoxicity docking apoptosis induction; Anti-lung cancer; Benzofuran derivatives; LSD1; Molecular docking; Structure-activity relationships.
A series of benzofurans I [R = 3-aminopropylamino, pyrrolidin-3-ylamino, piperazin-1-yl, etc.; Ar = pyrimidin-5-yl, p-tolyl, 1-methylindazol-5-yl, etc.] were designed, synthesized and biochem. evaluated as LSD1 inhibitors based on scaffold hopping and conformational restriction strategy. Most of the compounds I potently suppressed the enzymic activities of LSD1 and potently inhibited tumor cells proliferation. In particular, the representative compound I [R = (3S)-3-amino-1-piperidyl; Ar = p-tolyl] exhibited excellent LSD1 inhibition at the mol. levels with IC50 = 0.065μM, as well as anti-proliferation against MCF-7, MGC-803, H460, A549 and THP-1 tumor cells with IC50 values of 2.90 ± 0.32, 5.85 ± 0.35, 2.06 ± 0.27, 5.74 ± 1.03 and 6.15 ± 0.49μM, resp. The binding modes of these compounds I were rationalized by mol. docking. Meanwhile, a preliminary druggability evaluation showed that compound I [R = (3S)-3-amino-1-piperidyl; Ar = p-tolyl] displayed favorable liver microsomal stability and weak inhibitory activity against CYPs at 10μM. Remarkably, H460 xenograft tumors studies revealed that compound I [R = (3S)-3-amino-1-piperidyl; Ar = p-tolyl] demonstrated robust in-vivo antitumor efficacy without significant side effects. All the results demonstrated that compound I [R = (3S)-3-amino-1-piperidyl; Ar = p-tolyl] could represent a promising lead for further development.
European Journal of Medicinal Chemistry published new progress about Antitumor agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Synthetic Route of 73874-95-0.
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem