ArticleJournal of medicinal chemistry2010
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 animal models.
Article in Journal of medicinal chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 62 citations in OpenAlex.
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- Discovery, Optimization, and Characterization of ML417: A Novel and Highly Selective DJournal of medicinal chemistry · 2020Article
- Unsymmetrical Bisquinolines with High Potency againstMolecules (Basel, Switzerland) · 2020Article
- Targeting alpha synuclein and amyloid beta by a multifunctional, brain-penetrant dopamine D2/D3 agonist D-520: Potential therapeutic application in Parkinson's disease with dementia.Scientific reports · 2019Article
- A review on iron chelators as potential therapeutic agents for the treatment of Alzheimer's and Parkinson's diseases.Molecular diversity · 2019Review
- Receptor Ligands as Helping Hands to L-DOPA in the Treatment of Parkinson's Disease.Biomolecules · 2019Review
- Efficacy of Hybrid Tetrahydrobenzo[d]thiazole Based Aryl Piperazines D-264 and D-301 at D₂ and D₃ Receptors.Neurochemical research · 2016Article
- Development of a Highly Potent D2/D3 Agonist and a Partial Agonist from Structure-Activity Relationship Study of N(6)-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N(6)-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine Analogues: Implication in the Treatment of Parkinson's Disease.Journal of medicinal chemistry · 2015Article
- Article
- Multifunctional D2/D3 agonist D-520 with high in vivo efficacy: modulator of toxicity of alpha-synuclein aggregates.ACS chemical neuroscience · 2014Article
- 2-[2-(4-Methyl-piperazin-1-yl)eth-yl]iso-indoline-1,3-dione.Acta crystallographica. Section E, Structure reports online · 2014Article
- Structural modifications of neuroprotective anti-Parkinsonian (-)-N6-(2-(4-(biphenyl-4-yl)piperazin-1-yl)-ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264): an effort toward the improvement of in vivo efficacy of the parent molecule.Journal of medicinal chemistry · 2014Article
- Elucidation of structural elements for selectivity across monoamine transporters: novel 2-[(diphenylmethyl)sulfinyl]acetamide (modafinil) analogues.Journal of medicinal chemistry · 2014Article
- Synthesis andMedChemComm · 2013Article
- Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes.Neural regeneration research · 2013Review
- Modification of agonist binding moiety in hybrid derivative 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-1-ol/-2-amino versions: impact on functional activity and selectivity for dopamine D2/D3 receptors.Bioorganic & medicinal chemistry · 2013Article
- Structure-activity relationship study of N⁶-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N⁶-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine analogues: development of highly selective D3 dopamine receptor agonists along with a highly potent D2/D3 agonist and their pharmacological characterization.Journal of medicinal chemistry · 2012Article
- Homology modeling of dopamine D2 and D3 receptors: molecular dynamics refinement and docking evaluation.PloS one · 2012Article
- N-{2-[4-(2-Hy-droxy-eth-yl)piperazin-1-yl]eth-yl}phthalimide.Acta crystallographica. Section E, Structure reports online · 2012Article
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6 authors at 2 institutions in 1 country.
Funding
Abstract
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 carried out. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (K(i)). Functional activity of selected compounds in stimulating GTPgammaS binding was assessed with CHO cells expressing human D2 receptors and AtT-20 cells expressing human D3 receptors. SAR results identified compound (-)-24c (D-301) as one of the lead molecules with preferential agonist activity for D3 receptor (EC(50) (GTP gamma S); D3 = 0.52 nM; D2/D3 (EC(50)): 223). Compounds (-)-24b and (-)-24c exhibited potent radical scavenging activity. The two lead compounds, (-)-24b and (-)-24c, exhibited high in vivo activity in two Parkinson's disease (PD) animal models, reserpinized rat model and 6-OHDA induced unilaterally lesioned rat model. Future studies will explore potential use of these compounds in the neuroprotective therapy for PD.
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