Discovery of selective nanomolar inhibitors for insulin-regulated aminopeptidase based on α-hydroxy-β-amino acid derivatives of Bestatin was written by Vourloumis, Dionisios;Mavridis, Ioannis;Athanasoulis, Alexandros;Temponeras, Ioannis;Koumantou, Despoina;Giastas, Petros;Mpakali, Anastasia;Magrioti, Victoria;Leib, Jacqueline;van Endert, Peter;Stratikos, Efstratios;Papakyriakou, Athanasios. And the article was included in Journal of Medicinal Chemistry in 2022.COA of Formula: C4H4BrNO2 This article mentions the following:
The oxytocinase subfamily of M1 zinc aminopeptidases comprises emerging drug targets, including the ER-resident aminopeptidases 1 and 2 (ERAP1 and ERAP2) and insulin-regulated aminopeptidase (IRAP); however, reports on clin. relevant inhibitors are limited. Here we report a new synthetic approach of high diastereo- and regioselectivity for functionalization of the α-hydroxy-β-amino acid scaffold of bestatin. Stereochem. and mechanism of inhibition were investigated by a high-resolution X-ray crystal structure of ERAP1 in complex with a micromolar inhibitor. By exploring the P1 side-chain functionalities, we achieve significant potency and selectivity, and we report a cell-active, low-nanomolar inhibitor of IRAP with >120-fold selectivity over homologous enzymes. X-ray crystallog. anal. of IRAP in complex with this inhibitor suggest that interactions with the GAMEN loop is an unappreciated key determinant for potency and selectivity. Overall, our results suggest that α-hydroxy-β-amino acid derivatives may constitute useful chem. tools and drug leads for this group of aminopeptidases. In the experiment, the researchers used many compounds, for example, 1-Bromopyrrolidine-2,5-dione (cas: 128-08-5COA of Formula: C4H4BrNO2).
1-Bromopyrrolidine-2,5-dione (cas: 128-08-5) belongs to organobromine compounds. Organo bromine compounds are versatile compounds and are widely used in diverse fields. Organo bromine derivatives are used in the dye sector, as an indicator in analytical chemistry (Bromothymol blue is a popular indicator). In the pharmaceutical industry organo bromine derivatives are used as sedatives, vasodilators, antiseptic agents, and anticancer agents.COA of Formula: C4H4BrNO2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary