732973-87-4Relevant academic research and scientific papers
Synthesis of C4-Aminated Indoles via a Catellani and Retro-Diels-Alder Strategy
Zhang, Bo-Sheng,Li, Yuke,Zhang, Zhe,An, Yang,Wen, Yu-Hua,Gou, Xue-Ya,Quan, Si-Qi,Wang, Xin-Gang,Liang, Yong-Min
, p. 9731 - 9738 (2019/06/24)
Highly functionalized 4-aminoindoles were synthesized via the three-component cross-coupling of o-iodoaniline, N-benzoyloxyamines, and norbornadiene. The Catellani and retro-Diels-Alder strategy was used in this domino process. o-Iodoaniline, with electron-donating and sterically hindered protecting groups, made the reaction selective toward o-C-H amination. On the basis of density functional theory calculations, the intramolecular Buchwald coupling of this reaction underwent a dearomatization and a 1,3-palladium migration process. The reasons for the control of the chemical selectivity by the protecting groups are given. Moreover, synthetic applications toward 4-piperazinylindole and a GOT1 inhibitor were realized.
Synthesis of C4-Aminated Indoles via a Catellani and Retro-Diels-Alder Strategy
Zhang, Bo-Sheng,Li, Yuke,Zhang, Zhe,An, Yang,Wen, Yu-Hua,Gou, Xue-Ya,Quan, Si-Qi,Wang, Xin-Gang,Liang, Yong-Min
, (2019/06/24)
Highly functionalized 4-aminoindoles were synthesized via the three-component cross-coupling of o-iodoaniline, N-benzoyloxyamines, and norbornadiene. The Catellani and retro-Diels-Alder strategy was used in this domino process. o-Iodoaniline, with electron-donating and sterically hindered protecting groups, made the reaction selective toward o-C-H amination. On the basis of density functional theory calculations, the intramolecular Buchwald coupling of this reaction underwent a dearomatization and a 1,3-palladium migration process. The reasons for the control of the chemical selectivity by the protecting groups are given. Moreover, synthetic applications toward 4-piperazinylindole and a GOT1 inhibitor were realized.
Discovery and optimization of aspartate aminotransferase 1 inhibitors to target redox balance in pancreatic ductal adenocarcinoma
Anglin, Justin,Zavareh, Reza Beheshti,Sander, Philipp N.,Haldar, Daniel,Mullarky, Edouard,Cantley, Lewis C.,Kimmelman, Alec C.,Lyssiotis, Costas A.,Lairson, Luke L.
supporting information, p. 2675 - 2678 (2018/05/16)
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 molecule 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 ～800,000 molecules, 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 chemistry-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.
