74537-77-2Relevant academic research and scientific papers
Synthesis of 4,6-dimethylpyrimidine 2-thiosubstituted derivatives and their preliminary biological evaluation
Yengoyan, Aleksandr P.,Hambardzumyan, Elen N.,Vorskanyan, Asya S.,Shahbazyan, Lusya V.
, p. 311 - 317 (2021/04/28)
Based on 4,6-dimethylpyrimidine-2-thiol hydrochloride a series of its novel S-substituted derivatives including bi-and tricyclic heterosystems with a combination of azines and pyrazole cycles in the molecule were synthesized. The preliminary biological screening has shown that the obtained compounds have a pronounced plants growth-stimulating activity, which is a new property for these heterosystems. This fact indicates the prospectivity of further development of synthesized systems for the search for new plants growth stimulators.
Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure-Activity Relationship Study
Schiedel, Matthias,Rumpf, Tobias,Karaman, Berin,Lehotzky, Attila,Oláh, Judit,Gerhardt, Stefan,Ovádi, Judit,Sippl, Wolfgang,Einsle, Oliver,Jung, Manfred
, p. 1599 - 1612 (2016/03/05)
Sirtuins are NAD+-dependent protein deacylases that cleave off acetyl but also other acyl groups from the ε-amino group of lysines in histones and other substrate proteins. Dysregulation of human Sirt2 (hSirt2) activity has been associated with the pathogenesis of cancer, inflammation, and neurodegeneration, which makes the modulation of hSirt2 activity a promising strategy for pharmaceutical intervention. The sirtuin rearranging ligands (SirReals) have recently been discovered by us as highly potent and isotype-selective hSirt2 inhibitors. Here, we present a well-defined structure-activity relationship study, which rationalizes the unique features of the SirReals and probes the limits of modifications on this scaffold regarding inhibitor potency. Moreover, we present a crystal structure of hSirt2 in complex with an optimized SirReal derivative that exhibits an improved in vitro activity. Lastly, we show cellular hyperacetylation of the hSirt2 targeted tubulin caused by our improved lead structure.
