ArticleACS chemical neuroscience2012
Exploration of synthetic approaches and pharmacological evaluation of PNU-69176E and its stereoisomer as 5-HT2C receptor allosteric modulators.
Article in ACS chemical neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
The trial behind it
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
15 citing papers in PubMed, 30 citations in OpenAlex.
- Allosteric Modulators of Serotonin Receptors: A Medicinal Chemistry Survey.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Discovery of Novel Oleamide Analogues as Brain-Penetrant Positive Allosteric Serotonin 5-HTJournal of medicinal chemistry · 2023Article
- μ-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges.Frontiers in pharmacology · 2023Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Allosteric Modulators of G Protein-Coupled Dopamine and Serotonin Receptors: A New Class of Atypical Antipsychotics.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Discovery of 4-Phenylpiperidine-2-Carboxamide Analogues as Serotonin 5-HTJournal of medicinal chemistry · 2020Article
- Design, Synthesis, and Characterization of 4-Undecylpiperidine-2-carboxamides as Positive Allosteric Modulators of the Serotonin (5-HT) 5-HTJournal of medicinal chemistry · 2019Article
- Allosteric Modulation of Class A GPCRs: Targets, Agents, and Emerging Concepts.Journal of medicinal chemistry · 2019Review
- Targeting the 5-HT2C Receptor in Biological Context and the Current State of 5-HT2C Receptor Ligand Development.Current topics in medicinal chemistry · 2019Review
- Synthesis and activity of functionalizable derivatives of the serotonin (5-HT) 5-HTBioorganic & medicinal chemistry letters · 2018Article
- Synthesis and Structure-Activity Relationships of Tool Compounds Based on WAY163909, a 5-HTACS chemical neuroscience · 2017Article
- Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction.Neuropharmacology · 2014Review
- Peptide inhibitors disrupt the serotonin 5-HT2C receptor interaction with phosphatase and tensin homolog to allosterically modulate cellular signaling and behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Celebrating serotonin.ACS chemical neuroscience · 2012Article
- Allosteric Modulation of G Protein-Coupled Receptors: An Emerging Approach of Drug Discovery.Austin journal of pharmacology and therapeuticsArticle
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Allosteric modulators of the serotonin (5-HT) 5-HT(2C) receptor (5-HT(2C)R) present a unique drug design strategy to augment the response to endogenous 5-HT in a site- and event-specific manner with great potential as novel central nervous system probes and therapeutics. To date, PNU-69176E is the only reported selective positive allosteric modulator for the 5-HT(2C)R. For the first time, an optimized synthetic route to readily access PNU-69176E (1) and its diastereomer 2 has been established in moderate to good overall yields over 10 steps starting from commercially available picolinic acid. This synthetic approach not only enables a feasible preparation of a sufficient amount of 1 for use as a reference compound for secondary pharmacological studies, but also provides an efficient synthesis of key intermediates to develop novel and simplified 5-HT(2C)R allosteric modulators. Compound 1 and its diastereomer 2 were functionally characterized in Chinese hamster ovary (CHO) cells stably transfected with the 5-HT(2C)R using an intracellular calcium (Ca(i) (2+)) release assay. Compound 1 demonstrated efficacy and potency as an allosteric modulator for the 5-HT(2C)R with no intrinsic agonist activity. Compound 1 did not alter 5-HT-evoked Ca(i) (2+) in CHO cells stably transfected with the highly homologous 5-HT(2A)R. In contrast, the diastereomer 2 did not alter 5-HT-evoked Ca(i) (2+) release in 5-HT(2A)R-CHO or 5-HT(2C)R-CHO cells or exhibit intrinsic agonist activity.
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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.