ArticleJournal of medicinal chemistry2015
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.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 41 citations in OpenAlex.
- Indole Scaffolds in Neurological Therapeutics: Synthesis, Structure- Activity Relationships and Drug-Receptor Interactions.Mini reviews in medicinal chemistry · 2026Review
- Biological Characterization of the Anti-ferroptotic Properties of a Novel Anti-Parkinsonian Iron (II) Selective Dopamine Agonist, D-583.Neurochemical research · 2025Article
- Carbazole and tetrahydro-carboline derivatives as dopamine DActa pharmaceutica Sinica. B · 2023Article
- New Xanthone Derivatives as Potent G-Quadruplex Binders for Developing Anti-Cancer Therapeutics.ACS pharmacology & translational science · 2023Article
- Developing Photoaffinity Probes for Dopamine Receptor DACS chemical neuroscience · 2022Article
- Nanoparticle-Guided Brain Drug Delivery: Expanding the Therapeutic Approach to Neurodegenerative Diseases.Pharmaceutics · 2021Review
- Scaffold Hybridization Strategy Leads to the Discovery of Dopamine DACS chemical neuroscience · 2021Article
- Neuroprotective effects of Shende'an tablet in the Parkinson's disease model.Chinese medicine · 2021Article
- Dopamine D1 Receptor in Cancer.Cancers · 2020Review
- Nanocarriers as a powerful vehicle to overcome blood-brain barrier in treating neurodegenerative diseases: Focus on recent advances.Asian journal of pharmaceutical sciences · 2019Review
- Review
- Utilization of Biased G Protein-Coupled ReceptorSignaling towards Development of Safer andPersonalized Therapeutics.Molecules (Basel, Switzerland) · 2019Review
- Multitarget 1,4-Dioxane Compounds Combining Favorable DACS chemical neuroscience · 2019Article
- Advances and challenges in the search for DCellular signalling · 2018Review
- A novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-syn- and MPTP-induced toxicities in vivo.Neuropharmacology · 2017Article
- Functional Characterization of a Novel Series of Biased Signaling Dopamine D3 Receptor Agonists.ACS chemical neuroscience · 2017Article
- Synthesis and evaluation of C9 alkoxy analogues of (-)-stepholidine as dopamine receptor ligands.European journal of medicinal chemistry · 2017Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Our structure-activity relationship studies with 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 derivatives led to development of a lead compound (-)-21a which exhibited very high affinity (Ki, D2 = 16.4 nM, D3 = 1.15 nM) and full agonist activity (EC50 (GTPγS); D2 = 3.23 and D3 = 1.41 nM) at both D2 and D3 receptors. A partial agonist molecule (-)-34 (EC50 (GTPγS); D2 = 21.6 (Emax = 27%) and D3 = 10.9 nM) was also identified. In a Parkinson's disease (PD) animal model, (-)-21a was highly efficacious in reversing hypolocomotion in reserpinized rats with a long duration of action, indicating its potential as an anti-PD drug. Compound (-)-34 was also able to elevate locomotor activity in the above PD animal model significantly, implying its potential application in PD therapy. Furthermore, (-)-21a was shown to be neuroprotective in protecting neuronal PC12 from toxicity of 6-OHDA. This report, therefore, underpins the notion that a multifunctional drug like (-)-21a might have the potential not only to ameliorate motor dysfunction in PD patients but also to modify disease progression by protecting DA neurons from progressive degeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.