Dreas, Agnieszka; Kucwaj-Brysz, Katarzyna; Pyziak, Karolina; Kulesza, Urszula; Wincza, Ewelina; Fabritius, Charles-Henry; Michalik, Kinga; Gabor-Worwa, Ewelina; Golas, Aniela; Milik, Mariusz; Masiejczyk, Magdalena; Majewska, Eliza; Pysniak, Kazimiera; Wojcik-Trechcinska, Urszula; Sandowska-Markiewicz, Zuzanna; Brzozka, Krzysztof; Ostrowski, Jerzy; Rzymski, Tomasz; Mikula, Michal published an article in 2021. The article was titled 《Discovery of indazole-pyridinone derivatives as a novel class of potent and selective MNK1/2 kinase inhibitors that protecting against endotoxin-induced septic shock》, and you may find the article in European Journal of Medicinal Chemistry.Formula: C8H6BrN The information in the text is summarized as follows:
The mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (MNKs 1/2) and their downstream target eIF4E, play a role in oncogenic transformation, progression and metastasis. These results provided rationale for development of first MNKs inhibitors, currently in clin. trials for cancer treatment. Inhibitors of the MNKs/eIF4E pathway are also proposed as treatment strategy for inflammatory conditions. Here we present results of optimization of indazole-pyridinone derived MNK1/2 inhibitors among which compounds I and II, selective and metabolically stable derivatives Both compounds decreased levels of eIF4E Ser206 phosphorylation (pSer209-eIF4E) in MOLM16 cell line. When administered in mice compounds I and II significantly improved survival rates of animals in the endotoxin LD challenge model, with concomitant reduction of proinflammatory cytokine levels – TNFα and IL-6 in serum. Identified MNK1/2 inhibitors represent a novel class of immunomodulatory compounds with a potential for the treatment of inflammatory diseases including sepsis. The results came from multiple reactions, including the reaction of 4-Cyanobenzyl bromide(cas: 17201-43-3Formula: C8H6BrN)
4-Cyanobenzyl bromide(cas: 17201-43-3) is an important intermediate for pharmaceutical production. It can be used for the synthesis of a series of piperidine-linked aromatic diimidazolines, which have been synthesized as conformationally restricted congeners of the anti-Pneumocystis carinii (PCP) drug, Pentamidine.Formula: C8H6BrN
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts