Wu, Bin published the artcileDesign, synthesis, and biological evaluation of cyano-substituted 2,4-diarylaminopyrimidines as potent JAK3 inhibitors for the treatment of B-cell lymphoma, Category: nitriles-buliding-blocks, the main research area is anilinopyrimidinylaminobenzonitrile preparation JAK3 inhibition antiproliferative SAR docking cytotoxicity pharmacokinetic; 2,4-Diarylaminopyrimidines; B-cell lymphoma; JAK3 inhibitors.
A series of cyano-substituted 2,4-diarylaminopyrimidines I [X = F, Cl, CF3; R1 = 4-ethylpiperazin-1-yl, 2-ethyl-5-methyl-imidazol-1-ylmethyl; R2 = 2-CN, 3-CN, 4-CN] were designed and synthesized as potent non-covalent JAK3 inhibitors. Among the derivatives synthesized, I [X = Cl; R1 = 4-ethylpiperazin-1-yl, 2-morpholinoacetylamino; R2 = 2-CN, 3-CN, 4-CN] (IC50 = 22.86 nM), (IC50 = 21.58 nM), and (IC50 = 20.66 nM) demonstrated inhibitory potencies against JAK3 similar to the known JAK3 inhibitor tofacitinib (IC50 = 20.10 nM). Moreover, comp. I [X = Cl; R1 = 4-ethylpiperazin-1-yl; R2 = 4-CN] displayed potent anti-proliferative activities against Raji and Ramos cells, with IC50 values of 0.9255 μM and 1.405 μM,resp. In addition, comp. I [X = Cl; R1 = 4-ethylpiperazin-1-yl; R2 = 4-CN] demonstrated low toxicity in normal HBE (human bronchial epithelial cells, IC50 > 10 μΜ) and L-02 (human liver cells, IC50 = 3.104 μΜ) cells. Anal. of the mode of action by flow cytometry indicated that comp. I [X = Cl; R1 = 4-ethylpiperazin-1-yl; R2 = 4-CN] effectively arrested Raji cells at the G2/M phase. Taken together, these results suggested that comp. I [X = Cl; R1 = 4-ethylpiperazin-1-yl; R2 = 4-CN] was a promising candidate for development as a potential treatment for B-cell lymphoma.
Bioorganic Chemistry published new progress about Antiproliferative agents. 1885-29-6 belongs to class nitriles-buliding-blocks, name is 2-Aminobenzonitrile(Flakes or Chunks), and the molecular formula is C7H6N2, Category: nitriles-buliding-blocks.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts