Li, Zhang published the artcileDesign, synthesis and evaluation of novel diaryl-1,5-diazoles derivatives bearing morpholine as potent dual COX-2/5-LOX inhibitors and antitumor agents, Application In Synthesis of 622-40-2, the publication is European Journal of Medicinal Chemistry (2019), 168-184, database is CAplus and MEDLINE.
In this paper, 41 hybrid compounds containing diaryl-1,5-diazole and morpholine structures, compounds I [R1 = H, F, Me, etc.; R2 = H, F, Cl, etc.; X = O, S] and II [R3 = H, F, MeO, etc.; Y = O, NH; n = 2,3] acting as dual COX-2/5-LOX inhibitors have been designed, synthesized and biol. evaluated. Most of them showed potent antiproliferative activities and COX-2/5-LOX inhibitory in-vitro. Among them, compound II [R3 = CF3, Y = NH, n = 3] displayed the most potency against cancer cell lines (IC50 = 6.43-10.97 μM for F10, HeLa, A549 and MCF-7 cells), lower toxicity to non-cancer cells than celecoxib (A33: IC50 = 194.01 μM vs.celecoxib: IC50 = 97.87 μM for 293T cells), and excellent inhibitory activities on COX-2 (IC50 = 0.17 μM) and 5-LOX (IC50 = 0.68 μM). Meanwhile, the mol. modeling study was performed to position compound II [R3 = CF3, Y = NH, n = 3] into COX-2 and 5-LOX active sites to determine the probable binding models. Mechanistic studies demonstrated that compound II [R3 = CF3, Y = NH, n = 3] could block cell cycle in G2 phase and subsequently induced apoptosis of F10 cells. Furthermore, compound II [R3 = CF3, Y = NH, n = 3] could significantly inhibit tumor growth in F10-xenograft mouse model, and pharmacokinetic study of compound A33 indicated that it showed better stability in vivo. In general, compound II [R3 = CF3, Y = NH, n = 3] could be a promising candidate for cancer therapy.
European Journal of Medicinal Chemistry published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C6H13NO2, Application In Synthesis of 622-40-2.
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