1019-06-3Relevant academic research and scientific papers
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.
Mixed 5-HT1A/D-2 Activity of a New Model of Arylpiperazines: 1-Aryl-4-piperazines. 1. Synthesis and Structure-Activity Relationships
Perrone, Roberto,Berardi, Francesco,Colabufo, Nicola A.,Tortorella, Vincenzo,Fiorentini, Francesco,et al.
, p. 99 - 104 (2007/10/02)
A new model of 4-alkyl-1-arylpiperazines containing a terminal dihydronaphthalene fragment on the alkyl chain was synthesized in order to have mixed serotonergic and dopaminergic activity and to persue the recent alternative approaches to the discovery of novel antipsychotic and anxiolytic agents.Title compounds were evaluated for in vitro activity on dopamine D-2 and serotonin 5-HT1A and 5-HT2 receptors by radioreceptor binding assays.They show high nanomolar affinity for 5-HT1A, moderate affinity for D-2, and low affinity for 5-HT2 receptors, and in particular, two compounds, 4--1-(2-methoxyphenyl)piperazine (8) and 4--1-(2-pyridyl)piperazine (15), show values (nM) of IC50 = 2.0 and 1.4 for 5-HT1A and IC50 = 90.6 and 119.3 for D-2, respectively.Some in vivo behavioral studies show compound 8 to be an antagonist on 5-HT1A receptors.These first findings place the new arylpiperazines on the same level as that of the azaspirone class, e.g., 1-(2-methoxyphenyl)-4-piperazine (NAN-190) and buspirone.
