Reference of 6-Bromopyridin-3-amineIn 2020 ,《Synthesis of novel hybrid quinolino[4,3-b][1,5]naphthyridines and quinolino[4,3-b][1,5]naphthyridin-6(5H)-one derivatives and biological evaluation as topoisomerase I inhibitors and antiproliferatives》 appeared in European Journal of Medicinal Chemistry. The author of the article were Martin-Encinas, Endika; Selas, Asier; Tesauro, Cinzia; Rubiales, Gloria; Knudsen, Birgitta R.; Palacios, Francisco; Alonso, Concepcion. The article conveys some information:
The topoisomerase I enzymic inhibition of hybrid quinolino [4,3-b][1,5]naphthyridines I [R1 = H, 9-OMe, 9-Br, 11-Br; R2 = H, tosyl; X = CH2, CO] and quinolino [4,3-b][1,5]naphthyridin-6(5H)-ones II [R3 = H, 9-OMe, 9-Br, 11-Br; X = CH2, CO] were investigated. First, the synthesis of these fused compounds was performed by intramol. [4 + 2]-cycloaddition reaction of functionalized aldimines obtained by the condensation of 3-aminopyridine and unsaturated aldehydes afforded corresponding hybrid 5-tosylhexahydroquinolino [4,3-b][1,5]naphthyridines I [R2 = tosyl; X = CH2] tetrahydroquinolino [4,3-b][1,5]naphthyridin-6(5H)-one compound I [R2 = tosyl; X = CO] with good to high yields. Subsequent dehydrogenation led to the corresponding more unsaturated dihydro [1,5]naphthyridine II [X = CH2] and [1,5]naphthyridin-6(5H)-one derivs II [X = CO] in quant. yields. Deprotection of tosyl group in compounds I [R1 = H, 9-Br; R2 = tosyl; X = CH2] with magnesium in acidic conditions led to hexahydroquinolino[4,3-b][1,5]naphthyridines derivatives I [R1 = H, 9-Br; R2 = H; X = CH2]. The new polycyclic products compounds I and II showed excellent-good activity as topoisomerase I (TopI) inhibitors that lead to TopI induced nicking of plasmids. This was consistent with the compounds acted as TopI poisons resulting in the accumulation of trapped cleavage complexes in the DNA. The cytotoxic effect on cell lines A549, SKOV3 and on non-cancerous MRC5 was also screened. Compound I [R1 = H; R2 = tosyl; X = CO] resulted the most cytotoxic compound with IC50 values of 3.25 ± 0.91μM and 2.08 ± 1.89μM against the A549 cell line and the SKOV3 cell line, resp. Also, compounds I [R1 = H; R2 = tosyl; X = CH2] and II [R3 = H] showed good cytotoxicity against these cell lines. None of the compounds presented cytotoxic effects against non-malignant pulmonary fibroblasts (MRC-5).6-Bromopyridin-3-amine(cas: 13534-97-9Reference of 6-Bromopyridin-3-amine) was used in this study.
6-Bromopyridin-3-amine(cas: 13534-97-9) 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.Reference of 6-Bromopyridin-3-amine