Discovery and optimization of aspartate aminotransferase 1 inhibitors to target redox balance in pancreatic ductal adenocarcinoma was written by Anglin, Justin;Zavareh, Reza Beheshti;Sander, Philipp N.;Haldar, Daniel;Mullarky, Edouard;Cantley, Lewis C.;Kimmelman, Alec C.;Lyssiotis, Costas A.;Lairson, Luke L.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2018.Computed Properties of C8H4N2O This article mentions the following:
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is extremely refractory to the therapeutic approaches that have been evaluated to date. Recently, it has been demonstrated that PDAC tumors are dependent upon a metabolic pathway involving aspartate aminotransferase 1, also known as glutamate-oxaloacetate transaminase 1 (GOT1), for the maintenance of redox homeostasis and sustained proliferation. As such, small mol. inhibitors targeting this metabolic pathway may provide a novel therapeutic approach for the treatment of this devastating disease. To this end, from a high throughput screen of â?00,000 mols., 4-(1H-indol-4-yl)-N-phenylpiperazine-1-carboxamide was identified as an inhibitor of GOT1. Mouse pharmacokinetic studies revealed that potency, rather than inherent metabolic instability, would limit immediate cell- and rodent xenograft-based experiments aimed at validating this potential cancer metabolism-related target. Medicinal chem.-based optimization resulted in the identification of multiple derivatives with >10-fold improvements in potency, as well as the identification of a tryptamine-based series of GOT1 inhibitors. In the experiment, the researchers used many compounds, for example, 3-Cyanophenylisocyanate (cas: 16413-26-6Computed Properties of C8H4N2O).
3-Cyanophenylisocyanate (cas: 16413-26-6) belongs to esters. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Computed Properties of C8H4N2O
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics