151978-66-4Relevant articles and documents
Design of highly potent urea-based, exosite-binding inhibitors selective for glutamate carboxypeptidase II
Tykvart, Jan,Schimer, Ji?í,Jan?a?ík, Andrej,Ba?inková, Jitka,Navrátil, Václav,Starková, Jana,?rámková, Karolína,Konvalinka, Jan,Majer, Pavel,?ácha, Pavel
, p. 4357 - 4363 (2015)
We present here a structure-aided design of inhibitors targeting the active site as well as exosites of glutamate carboxypeptidase II (GCPII), a prostate cancer marker, preparing potent and selective inhibitors that are more than 1000-fold more active tow
Multifunctional D2/D3 agonist D-520 with high in vivo efficacy: Modulator of toxicity of alpha-synuclein aggregates
Modi, Gyan,Voshavar, Chandrashekhar,Gogoi, Sanjib,Shah, Mrudang,Antonio, Tamara,Reith, Maarten E. A.,Dutta, Aloke K.
, p. 700 - 717 (2014/11/08)
We have developed a series of dihydroxy compounds and related analogues based on our hybrid D2/D3 agonist molecular template to develop multifunctional drugs for symptomatic and neuroprotective treatment for Parkinson"s disease (PD). The lead compound (-)-24b (D-520) exhibited high agonist potency at D2/D3 receptors and produced efficacious activity in the animal models for PD. The data from thioflavin T (ThT) assay and from transmission electron microscopy (TEM) analysis demonstrate that D-520 is able to modulate aggregation of alpha-synuclein (αSN). Additionally, coincubation of D-520 with αSN is able to reduce toxicity of preformed aggregates of αSN compared to control αSN alone. Finally, in a neuroprotection study with dopaminergic MN9D cells, D-520 clearly demonstrated the effect of neuroprotection from toxicity of 6-hydroxydopamine. Thus, compound D-520 possesses properties characteristic of multifunctionality conducive to symptomatic and neuroprotective treatment of PD.
Development of (S)-N6-(2-(4-(isoquinolin-1-yl)piperazin-1-yl) ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]-thiazole-2,6-diamine and its analogue as a D3 receptor preferring agonist: Potent in vivo activity in Parkinson's disease anima
Ghosh, Balaram,Antonio, Tamara,Zhen, Juan,Kharkar, Prashant,Reith, Maarten E. A.,Dutta, Aloke K.
experimental part, p. 1023 - 1037 (2010/08/06)
Here we report structure - activity relationship study of a novel hybrid series of compounds where structural alteration of aromatic hydrophobic moieties connected to the piperazine ring and bioisosteric replacement of the aromatic tetralin moieties were