Based on 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474), design, synthesis and biological evaluation of novel PI3Kα selective inhibitors

Overview of CFTR activators and their recent studies for dry eye disease: a review

“…3.2 1,3,5-Triazine 1,3,5-Triazine derivatives have been extensively studied for their diverse pharmacological profile and significant industrial applications. [64][65][66] In a recent study, Flores et al identified a novel class of small molecule activators of wildtype CFTR through HTS, specifically aminophenyl-1,3,5triazine compounds. Notably, one compound from the screening, 60 (CFTRact-K089) (Fig.…”

Recent biological applications of heterocyclic hybrids containing s-triazine scaffold

“…To evaluate the anticancer activities of s-triazine, its three distinct series in conjunction with benzimidazole (42) were prepared and its inhibitor effect against P13Ka-b-g-d, and three cancer cell- lines, namely, U87-MG, MCF-7, and PC-3 were evaluated. 49 SAR showed that compounds with R 1 containing 2,4-diuoro substituent and R 2 being H showed maximum inhibition effect this may be due to the fact that these two uorine atoms can show more electron-withdrawing effect on the phenyl ring and make it more susceptible to p-p interactions. Cytotoxicity of these compounds was evaluated to be U87-MG = 0.70 ± 0.10 mM, MCF-7 = 0.13 ± 0.02 mM, PC-3 = 0.57 ± 0.15 mM, PI3Ka = 0.32 ± 0.18 nM, PI3Kb = >100 nM, PI3Kg = 16.03 ± 3.55 nM, and PI3Kd = >100 nM.…”

Design and Synthesis of 1,3,5-Triazines or Pyrimidines Containing Dithiocarbamate Moiety as PI3Kα Selective Inhibitors

“…36 According to the docking results of the ZSTK-474 reported in the literature, a morpholine oxygen atom could form a hydrogen bond with residue Val851 in the PI3K hinge region, and the 1,3,5-triazine group acts as an adenosine mimic (Figure 3B). 37 However, because the other morpholine group does not have the length to extend into the protein solvent region, it cannot form a hydrogen bond with the specific residue Glu859 of PI3Kα, as shown in Figure 3B. Consequently, ZSTK-474 displayed no subtype selectivity.…”

“…We focused on the properties and length of R substituents in order to explore the structure-activity relation (SAR). According to the reported literature, if the distance between dithiocarbamate and small molecular amine “tail” is two carbon atoms, the optimal binding effect is better . Therefore, we introduced a two-carbon-atom linker in an attempt to obtain better activity.…”

“…According to the reported literature, if the distance between dithiocarbamate and small molecular amine "tail" is two carbon atoms, the optimal binding effect is better. 39 Therefore, we introduced a two-carbon-atom linker in an attempt to obtain better activity.…”