In 2019,European Journal of Medicinal Chemistry included an article by Martin-Encinas, Endika; Rubiales, Gloria; Knudssen, Birgitta R.; Palacios, Francisco; Alonso, Concepcion. Synthetic Route of C5H5BrN2. The article was titled 《Straightforward synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents of hybrid chromeno[4,3-b][1,5]naphthyridines and chromeno[4,3-b][1,5]naphthyridin-6-ones》. The information in the text is summarized as follows:
Hybrid tetrahydrochromeno[4,3-b][1,5]naphthyridines I [R1 = H, F, Me; R2 = H, OMe; X = CH2], tetrahydrochromeno[4,3-b][1,5]naphthyridinones I [R1 = H, F; R2 = H, OMe, Br; X = C(O)], chromeno[4,3-b][1,5]naphthyridines II [X = CH2] and chromeno[4,3-b][1,5]naphthyridinones II [R3 = H, F, Me; R4 = H, OMe, Br; R5 = Ph, 4-MeOC6H4, 3,4-F2C6H3; Z = CH2, C(O)] were synthesized and evaluated as topoisomerase I inhibitors and antiproliferative agents. The synthetic route involved an intramol. Povarov [4 + 2]-cycloaddition of functionalized aldimines obtained by the condensation of 3-aminopyridine and aldehydes containing a double or triple carbon-carbon bond in ortho position and allowed the selective generation of three stereogenic centers. The subsequent dehydrogenation of the fused tetrahydrochromeno[4,3-b][1,5]naphthyridines I [X = CH2] and tetrahydrochromeno[4,3-b][1,5]naphthyridin-6-ones I [X = C=O] led to the formation of the corresponding tetracyclic chromeno[4,3-b][1,5]naphthyridine derivatives II [X = CH2] and chromeno[4,3-b][1,5]naphthyridin-6-ones II [X = C=O] in quant. yields. Some of the prepared products showed activity as inhibitors of topoisomerase I (TopI). Addnl., the cytotoxic behavior of these compounds was studied and the absence of cytotoxicity was observed against non-cancerous lung fibroblasts cell line (MRC5). Compound tetrahydrochromeno[4,3-b][1,5]naphthyridine I [R1 = R3 = H, R2 = Ph, X = CH2] showed excellent cytotoxic activity with a IC50 value of 1.03 ± 0.30 μM against the A549 cell line and a IC50 value of 1.75 ± 0.20 μM against the SKOV03 cell line. The obtained results point to these compounds as good antiproliferative candidates. Further, the physicochem. properties of these hybrid compounds were evaluated and could be considered as candidates for drugs with promising pharmacotherapeutic profiles similar to those of currently used drugs. In addition, docking experiments showed the possible mode of binding of these compounds and according to these studies the structural part corresponding to chromene or coumarin seems to play an important role in the interaction with the active site. The results came from multiple reactions, including the reaction of 6-Bromopyridin-3-amine(cas: 13534-97-9Synthetic Route of C5H5BrN2)
6-Bromopyridin-3-amine(cas: 13534-97-9) belongs to anime. Halogenation, in which one or more hydrogen atoms of an amine is replaced by a halogen atom, occurs with chlorine, bromine, and iodine, as well as with some other reagents, notably hypochlorous acid (HClO). With primary amines the reaction proceeds in two stages, producing N-chloro- and N,N-dichloro-amines, RNHCl and RNCl2, respectively. With tertiary amines, an alkyl group may be displaced by a halogen.Synthetic Route of C5H5BrN2