Design, synthesis, docking, molecular dynamics and bioevaluation studies on novel N-methylpicolinamide and thienopyrimidine derivatives with inhibiting NF-κB and TAK1 activities: Cheminformatics tools RDKit applied in drug design was written by Wang, Linxiao;Zhang, Qian;Wang, Zhe;Zhu, Wufu;Tan, Ninghua. And the article was included in European Journal of Medicinal Chemistry in 2021.Safety of 4-(2-Chloropyrimidin-4-yl)morpholine This article mentions the following:
Using cheminformatics tools RDKit and literature investigation, four series of 24 thienopyrimidine I [X = C, C=O; Y = H, N(Me)2, N(Et)2] II [R = H, Me; R2 = pyrrolidin-1-yl, 1-piperidyl, morpholino, indolin-1-yl, 3,4-dihydro-1H-isoquinolin-2-yl] III and N-methylpicolinamide derivatives IV [R2 = pyrrolidin-1-yl, 1-piperidyl, morpholino, 3,4-dihydro-1H-isoquinolin-2-yl] substituted with pyrimidine were designed, synthesized and evaluated for activities against three cancer cell lines (MDA-MB-231, HCT116 and A549), TAK1 kinase and NF-κB signaling pathway. Almost all compounds I, II, III, IV showed selectivity toward the A549 cell lines and the most promising compound IV [R2 = 1-piperidyl] could inhibit TAK1 kinase and NF-κB signaling pathway with the IC50 values of 0.58 and 0.84μM. Moreover, IV [R2 = 1-piperidyl] could induce cell cycle arrest of A549 cells at the G2/M checkpoint with 30.57% and induce apoptosis (34.94%) in a concentration-dependent manner. And western blot showed that compound IV [R2 = 1-piperidyl] could inhibit TNF-α-induced IκBα phosphorylation, IκBα degradation, p65 phosphorylation and TAK1 phosphorylation, and reduce the expression of p65. The studies of docking, mol. dynamics, MM/PBSA and frequency anal. theor. supported the conclusions of the bioevaluation. In the experiment, the researchers used many compounds, for example, 4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0Safety of 4-(2-Chloropyrimidin-4-yl)morpholine).
4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0) belongs to pyrimidine derivatives. Heterocyclic compounds bearing the pyrimidine core are of tremendous interest as they constitute an important class of natural and synthetic compounds exhibiting diverse useful biological activities that hold attractive potential for clinical translation as therapeutic agents in alleviation of a myriad of diseases. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.Safety of 4-(2-Chloropyrimidin-4-yl)morpholine
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia