Kowol, Christian R. published the artcileImpact of Stepwise NH2-Methylation of Triapine on the Physicochemical Properties, Anticancer Activity, and Resistance Circumvention, Safety of 2-Bromopyridin-3-amine, the publication is Journal of Medicinal Chemistry (2016), 59(14), 6739-6752, database is CAplus and MEDLINE.
One of the most promising classes of iron chelators are α-N-heterocyclic thiosemicarbazones with Triapine as the most prominent representative. In several clin. trials Triapine showed anticancer activity against hematol. diseases, however, studies on solid tumors failed due to widely unknown reasons. Some years ago, it was recognized that “terminal dimethylation” of thiosemicarbazones can lead to a more than 100-fold increased activity, probably due to interactions with cellular copper depots. To better understand the structural requirements for the switch to nanomolar cytotoxicity, we systematically synthesized all eight possible N-methylated derivatives of Triapine and investigated their potential against Triapine-sensitive as well as -resistant cell lines. While only the “completely” methylated compound exerted nanomolar activity, the data revealed that all compounds with at least one N-dimethylation were not affected by acquired Triapine resistance. In addition, these compounds were highly synergistic with copper treatment accompanied by induction of reactive oxygen species and massive necrotic cell death.
Journal of Medicinal Chemistry published new progress about 39856-58-1. 39856-58-1 belongs to pyridine-derivatives, auxiliary class Pyridine,Bromide,Amine, name is 2-Bromopyridin-3-amine, and the molecular formula is C5H5BrN2, Safety of 2-Bromopyridin-3-amine.
Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem