ArticleJournal of medicinal chemistry2013
Structure-activity relationship of N,N'-disubstituted pyrimidinetriones as Ca(V)1.3 calcium channel-selective antagonists for Parkinson's disease.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- The L-type calcium channel CaV1.3: A potential target for cancer therapy.Journal of cellular and molecular medicine · 2024Review
- Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine co-varies with risk factors for Parkinson's.The European journal of neuroscience · 2024Article
- Quinpirole inhibits levodopa-induced dyskinesias at structural and behavioral levels: Efficacy negated by co-administration of isradipine.Experimental neurology · 2023Article
- CaBritish journal of pharmacology · 2023Review
- The Role of Striatal Cav1.3 Calcium Channels in Therapeutics for Parkinson's Disease.Handbook of experimental pharmacology · 2023Review
- Palladium-Catalyzed α-Arylation of Cyclic β-Dicarbonyl Compounds for the Synthesis of CaACS omega · 2022Article
- The Involvement of CaFrontiers in neural circuits · 2021Article
- Investigation of the Selectivity of L-Type Voltage-Gated Calcium Channels 1.3 for Pyrimidine-2,4,6-Triones Derivatives Based on Molecular Dynamics Simulation.Molecules (Basel, Switzerland) · 2020Article
- A Single Amino Acid Determines the Selectivity and Efficacy of Selective Negative Allosteric Modulators of CaACS chemical biology · 2020Article
- Genetic silencing of striatal CaV1.3 prevents and ameliorates levodopa dyskinesia.Movement disorders : official journal of the Movement Disorder Society · 2019Article
- Molecular Determinants of the Differential Modulation of CaMolecular pharmacology · 2018Article
- Mechanism-specific assay design facilitates the discovery of Nav1.7-selective inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Converging roles of ion channels, calcium, metabolic stress, and activity pattern of Substantia nigra dopaminergic neurons in health and Parkinson's disease.Journal of neurochemistry · 2016Review
- L-type calcium channels as drug targets in CNS disorders.Channels (Austin, Tex.) · 2016Review
- The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential.Pharmacological reviews · 2015Review
- Pharmacology of L-type Calcium Channels: Novel Drugs for Old Targets?Current molecular pharmacology · 2015Review
- Pyrimidine-2,4,6-triones are a new class of voltage-gated L-type Ca2+ channel activators.Nature communications · 2014Article
- Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase.Nature neuroscience · 2014Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
CaV1.3 L-type calcium channels (LTCCs) have been a potential target for Parkinson's disease since calcium ion influx through the channel was implicated in the generation of mitochondrial oxidative stress, causing cell death in the dopaminergic neurons. Selective inhibition of CaV1.3 over other LTCC isoforms, especially CaV1.2, is critical to minimize potential side effects. We recently identified pyrimidinetriones (PYTs) as a CaV1.3-selective scaffold; here we report the structure-activity relationship of PYTs with both CaV1.3 and CaV1.2 LTCCs. By variation of the substituents on the cyclopentyl and arylalkyl groups of PYT, SAR studies allowed characterization of the CaV1.3 and CaV1.2 LTCCs binding sites. The SAR also identified four important moieties that either retain selectivity or enhance binding affinity. Our study represents a significant enhancement of the SAR of PYTs at CaV1.3 and CaV1.2 LTCCs and highlights several advances in the lead optimization and diversification of this family of compounds for drug development.
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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.