Li, Zhe; Gever, Joel R.; Rao, Satish; Widjaja, Kartika; Prusiner, Stanley B.; Silber, B. Michael published the artcile< Discovery and Preliminary Structure-Activity Relationship of Arylpiperazines as Novel, Brain-Penetrant Antiprion Compounds>, HPLC of Formula: 197638-83-8, the main research area is arylpiperazine antiprion neurodegenerative disease creutzfeldt jakob preparation; Creutzfeldt-Jakob disease; Neurodegenerative diseases; SAR; arylpiperazine; piperazine; prion disease.
Creutzfeldt-Jakob disease and kuru in humans, BSE in cattle, and scrapie in sheep are fatal neurodegenerative disorders. Such illnesses are caused by the conversion and accumulation of a misfolded pathogenic isoform (termed PrPSc) of a normally benign, host cellular protein, denoted PrPC. The authors employed high-throughput screening enzyme-linked immunosorbent assays to evaluate compounds for their ability to reduce the level of PrPSc in Rocky Mountain Laboratory prion-infected mouse neuroblastoma cells (ScN2a-cl3). Arylpiperazines were among the active compounds identified, but the initial hits suffered from low potency and poor drug-likeness. The best of those hits, such as 1-(4-(4-Benzylpiperazine-1-yl)phenyl)ethanone, 1-(4-(4-(3-pyridinylmethyl)-1-piperazinyl)phenyl)ethanone, 1-(4-(4-(2-thienylmethyl)-1-piperazinyl)phenyl)ethanone, and 1-(4-(4-[(5-methyl-2-furanyl)methyl]-1-piperazinyl)phenyl)ethanone, displayed moderate antiprion activity with EC50 values in the micromolar range. Key analogs were designed and synthesized on the basis of the structure-activity relationship, with analogs 2-(4-(4-(Pyridin-3-ylmethyl)piperazin-1-yl)phenyl)benzo[d]oxazole, 2-(4-(4-(Pyridin-3-ylmethyl)piperazin-1-yl)phenyl)benzo[d]thiazole, 2-(4-(4-((6-Fluoropyridin-3-yl)methyl)piperazin-1-yl)phenyl)benzo[d]oxazole, and 2-(4-(4-((6-methoxypyridin-3-yl)methyl)piperazin-1-yl)phenyl)benzo[d]oxazole found to have submicromolar potency. Analogs 2-(4-(4-(Pyridin-3-ylmethyl)piperazin-1-yl)phenyl)benzo[d]oxazole and 2-(4-(4-(Pyridin-3-ylmethyl)piperazin-1-yl)phenyl)benzo[d]thiazole were able to penetrate the blood-brain barrier and achieved excellent drug concentrations in the brains of mice after oral dosing. These compounds represent good starting points for further lead optimization in the authors’ pursuit of potential drug candidates for the treatment of prion diseases.
ACS Medicinal Chemistry Letters published new progress about Creutzfeldt-Jakob disease. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, HPLC of Formula: 197638-83-8.
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics