Name: Piperidine-4-carboxamideOn October 15, 2020 ,《Design, synthesis and bioevaluation of novel substituted triazines as potential dual PI3K/mTOR inhibitors》 was published in European Journal of Medicinal Chemistry. The article was written by Wu, Ting-Ting; Guo, Qing-Qing; Chen, Zi-Li; Wang, Li-Li; Du, Yao; Chen, Rui; Mao, Yuan-Hu; Yang, Sheng-Gang; Huang, Jing; Wang, Jian-Ta; Wang, Ling; Tang, Lei; Zhang, Ji-Quan. The article contains the following contents:
A series of novel substituted triazines bearing a benzimidazole scaffold I [R = morpholino, 4-methylpiperazin-1-yl, ((1S)-2-amino-1-methyl-2-oxo-ethyl)amino, etc.] were designed and synthesized based on the structures of known anti-cancer agents, namely gedatolisib and alpelisib. All the target compounds were screened for inhibitory activity against PI3Kα and mTOR kinases. Notably, most analogs exhibited IC50 in the nanomolar range. Investigation of the isoenzyme selectivity indicated that the compounds exhibited remarkable inhibitory activity against PI3Kδ, especially compound I [R = 4-carbamoyl-1-piperidyl] showed an IC50 value of 2.3 nM for PI3Kδ and moderate δ-isoenzyme selectivity over other class I PI3K isoforms and mTOR (with IC50 values of 14.6, 34.0, 849.0 and 15.4 nM for PI3Kα, β, γ and mTOR, resp.). An in vitro MTT assay was conducted to assess the antiproliferative and cytotoxic effects of the prepared analogs. It was revealed that the compounds displayed significant inhibitory activities against the HCT116 human colon cancer cell line. Compound I [R = morpholino] showed 4.7-fold higher potency than the pos. control gedatolisib (0.3 vs. 1.4μM, IC50 values). Phosphoblot studies demonstrated that I [R = morpholino, (2R)-2-carbamoylpyrrolidin-1-yl] could significantly suppress the PI3K/Akt/mTOR signaling pathway at 10μM. Moreover, analogs I [R = morpholino, (2S)-2-carbamoylpyrrolidin-1-yl, (2R)-2-carbamoylpyrrolidin-1-yl] displayed better stability in artificial gastric fluids than gedatolisib, while I [R = morpholino] was indicated not very stable in rat liver microsomes, and may occur phase I metabolic transformations. After reading the article, we found that the author used Piperidine-4-carboxamide(cas: 39546-32-2Name: Piperidine-4-carboxamide)
Piperidine-4-carboxamide(cas: 39546-32-2) belongs to anime. Hydrogen peroxide (H2O2) and peroxy acids generally add an oxygen atom to the nitrogen of amines. With primary amines, this step is normally followed by further oxidation, leading to nitroso compounds, RNO, or nitro compounds, RNO2. Secondary amines are converted to hydroxylamines, R2NOH, and tertiary amines to amine oxides, R3NO.Name: Piperidine-4-carboxamide
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem