ArticleJournal of medicinal chemistry2014
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.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 33 citations in OpenAlex.
- Approach to the specificity and selectivity between D2 and D3 receptors by mutagenesis and binding experiments part I: Expression and characterization of D2 and D3 receptor mutants.Protein science : a publication of the Protein Society · 2022Article
- Cysteine Donor-Based Brain-Targeting Prodrug: Opportunities and Challenges.Oxidative medicine and cellular longevity · 2022Review
- Review
- Exploring the Multi-Target Neuroprotective Chemical Space of Benzofuran Scaffolds: A New Strategy in Drug Development for Alzheimer's Disease.Frontiers in pharmacology · 2019Review
- Advances and challenges in the search for DCellular signalling · 2018Review
- Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2016Review
- 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
- Multicomponent Synthesis and Biological Evaluation of a Piperazine-Based Dopamine Receptor Ligand Library.ACS medicinal chemistry letters · 2015Article
- Multifunctional D2/D3 agonist D-520 with high in vivo efficacy: modulator of toxicity of alpha-synuclein aggregates.ACS chemical neuroscience · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In our overall goal to develop multifunctional dopamine D2/D3 agonist drugs for the treatment of Parkinson's disease (PD), we previously synthesized potent D3 preferring agonist D-264 (1a), which exhibited neuroprotective properties in two animal models of PD. To enhance the in vivo efficacy of 1a, a structure-activity relationship study was carried out. Competitive binding and [(35)S]GTPγS functional assays identified compound (-)-9b as one of the lead molecules with preferential D3 agonist activity (EC50(GTPγS); D3 = 0.10 nM; D2/D3 (EC50): 159). Compounds (-)-9b and (-)-8b exhibited high in vivo activity in two PD animal models, reserpinized and 6-hydroxydopamine (OHDA)-induced unilateral lesioned rats. On the other hand, 1a failed to show any in vivo activity in these models unless the compound was dissolved in 5-10% beta-hydroxy propyl cyclodextrin solution. Lead compounds exhibited appreciable radical scavenging activity. In vitro experiments with dopaminergic MN9D cells indicated neuroprotection by both 1a and (-)-9b from toxicity of MPP+.
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