90437-76-6Relevant articles and documents
1-Benzyl-3-aryl-2-thiohydantoin Derivatives as New Anti-Trypanosoma brucei Agents: SAR and in Vivo Efficacy
Buchynskyy, Andriy,Gillespie, J. Robert,Herbst, Zackary M.,Ranade, Ranae M.,Buckner, Frederick S.,Gelb, Michael H.
supporting information, p. 886 - 891 (2017/08/16)
A high throughput screening and subsequent hit validation identified compound 1 as an inhibitor of Trypanosoma brucei parasite growth. Extensive structure-activity relationship optimization based on antiparasitic activity led to the highly potent compounds, 1-(4-fluorobenzyl)-3-(4-dimethylamino-3-chlorophenyl)-2-thiohydantoin (68) and 1-(2-chloro-4-fluorobenzyl)-3-(4-dimethylamino-3-methoxyphenyl)-2-thiohydantoin (76), with a T. brucei EC50 of 3 and 2 nM, respectively. This represents >100-fold improvement in potency compared to compound 1. In vivo efficacy experiments of 68 and 76 in an acute mouse model of Human African Trypanosomiasis showed a 100% cure rate after 4 days of oral treatment at 50 mg/kg twice per day.
Isoindol-1,3-dione and isoindol-1-one derivatives with high binding affinity to β-amyloid fibrils
Lee, Hyu Ji,Lim, Soo Jeong,Oh, Seung Jun,Moon, Dae Hyuk,Kim, Dong Jin,Tae, Jinsung,Yoo, Kyung Ho
, p. 1628 - 1631 (2008/09/19)
Based on the structural features of Indoprofen and PIB, a series of isoindol-1,3-diones 1a-k and isoindol-1-ones 2a-l were designed and synthesized. These 23 compounds were evaluated by competitive binding assay against aggregated Aβ42 fibrils using [125I]TZDM. All the isoindolone derivatives showed very good binding affinities with Ki values in the subnanomolar range (0.42-0.94 nM). Among them, isoindol-1,3-diones 1i and 1k and isoindol-1-ones 2c and 2i exhibited excellent binding affinities (Ki = 0.42-0.44 and 0.46-0.49 nM) than those of Indoprofen (Ki = 0.52 nM) and PIB (Ki = 0.70 nM). These results suggest that isoindolones could be served as a scaffold for potential AD diagnostic probes to monitor Aβ fibrils.
NITROPHENYL ETHERS AS POSSIBLE PHOTOAFFINITY LABELS. THE NUCLEOPHILIC AROMATIC PHOTOSUBSTITUTION REVISITED.
Cervello, J.,Figueredo, M.,Marquet, J.,Moreno-Manas, M.,Bertran, J.,Lluch, J. M.
, p. 4147 - 4150 (2007/10/02)
The photoreactions of nitrophenyl ethers with simple primary and secondary amines show a remarkable nucleophile influence on the reaction orientation.Calculations indicate a change from charge controlled to frontier orbital controlled reactions moving from smaller to larger amines.
