Design, Synthesis, and Cytoprotective Effect of 2-Aminothiazole Analogues as Potent Poly(ADP-Ribose) Polymerase-1 Inhibitors

A series of novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors were designed within 2-aminothiazole analogues (4−10) based on a constructed three-dimensional pharmacophore model. After synthesis, the inhibitory effect on PARP-1 activity and the cytoprotective action of these compounds were tested and evaluated. Among them, compounds 4−6 and 10 appeared to be potent PARP-1 inhibitors with IC50 values less than 1 μM, which had been perfectly predicted by pharmacophore model. These compounds proved to be highly potent against cell injury induced by H2O2 and oxygen-glucose deprivation (OGD) in PC12 cells. These novel 2-aminothiazole analogues are potentially applicable as neuroprotective agents for the treatment of neurological diseases.