65766-72-5Relevant articles and documents
Synthesis, spectroscopic, structural and conformational study of some tri-substituted ureas derived from N-methylpiperazine containing phenyl and N-heterocyclic substituents
Iriepa,Bellanato
, p. 215 - 220 (2013)
A series of tri-substituted ureas containing an N-methylpiperazine moiety as well as phenyl and N-heterocyclic substituents were synthesized and studied by 1H, 13C NMR and IR spectroscopies. From 1H and 13C NMR data, in CDCl3 solution at room temperature, a fast inter-conversion of the piperazine ring with the N-CH3 group in equatorial position can be proposed. Amino-imino tautomerism is observed for both thiazole and benzothiazole derivatives. Moreover, with the exception of the imino form of the thiazole derivative, the aryl substituted N-carbamoyl group rotates freely. IR data show that the compounds adopt a planar trans conformation of the CONH moiety.
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.
Studies in Potential Filaricides: Part 19 - Synthesis of 1-Methyl-4-substituted Carbonylpiperazines as Diethylcarbamazine Analogs
Sharma, Satyavan,Agarwal, V. K.,Dubey, S. K.,Iyer, R. N.,Anand, Nitya,et al.
, p. 748 - 751 (2007/10/02)
The synthesis and antifilarial activity of a series of 1-methyl-4-substituted carbamoyl- and carbonylpiperazines (6 - 42) against Litomosoides carinii in cotton rats and Dipetalonema viteae in Mastomys natalensis are described.The most potent compound of this series, 1-methyl-4-(pyrrolidin-1-yl)carbonylpiperazine (7) causes 95 - 98 percent reduction of blood microfilarial count in cotton rats infected with L. carinii at an intraperitoneal or oral dose of 1.5 (base) or 3 (citrate) mg/kg given for 6 days.A number of other compounds also exhibit marked microfilaricidal efffect in the dose range of 6 - 30 mg/kg.
