ArticleBioorganic & medicinal chemistry2016
Dissection of N,N-diethyl-N'-phenylpiperazines as α7 nicotinic receptor silent agonists.
Article in Bioorganic & medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Putative α7-selective ligands interact with α9-containing nicotinic acetylcholine receptors and modulate immune functions of human mononuclear phagocytes.Frontiers in immunology · 2026Article
- The Functional Topology of Phenylpiperazinium Agonists and Antagonists on the Nicotinic Acetylcholine Receptor Landscape: Pointing the Way for Future Therapeutic Management of Inflammation and Neuropathic Pain.ACS chemical neuroscience · 2025Article
- Variations in "Functional Site" Residues and Classification of Three-Finger Neurotoxins in Snake Venoms.Toxins · 2025Review
- Stereoisomers of Chiral Methyl-Substituted Symmetric and Asymmetric Aryl Piperazinium Compounds Exhibit Distinct Selectivity for α9 and α7 Nicotinic Acetylcholine Receptors.ACS chemical neuroscience · 2025Article
- Explorations of Agonist Selectivity for the α9* nAChR with Novel Substituted Carbamoyl/Amido/Heteroaryl Dialkylpiperazinium Salts and Their Therapeutic Implications in Pain and Inflammation.Journal of medicinal chemistry · 2024Article
- New Alpha9 nAChR Ligands Based on a 5-(Quinuclidin-3-ylmethyl)-1,2,4-oxadiazole Scaffold.ACS chemical neuroscience · 2024Article
- Pharmacological profiles and anti-inflammatory activity of pCN-diEPP and mCN-diEPP, new alpha9alpha10 nicotinic receptor ligands.Neuropharmacology · 2023Article
- Insights Into the Differential Desensitization ofMolecular pharmacology · 2023Article
- Coffee and cigarettes: Modulation of high and low sensitivity α4β2 nicotinic acetylcholine receptors by n-MP, a biomarker of coffee consumption.Neuropharmacology · 2022Article
- Selective Agonists and Antagonists of α9 Versus α7 Nicotinic Acetylcholine Receptors.ACS chemical neuroscience · 2022Article
- Sulfonium Ligands of the α7 nAChR.Molecules (Basel, Switzerland) · 2021Article
- Therapeutic Targeting ofPharmacological reviews · 2021Review
- Design, synthesis, and electrophysiological evaluation of NS6740 derivatives: Exploration of the structure-activity relationship for alpha7 nicotinic acetylcholine receptor silent activation.European journal of medicinal chemistry · 2020Article
- Nicotinic receptor pharmacology in silico: Insights and challenges.Neuropharmacology · 2020Review
- A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE.Brain, behavior, and immunity · 2020Article
- H/D Exchange Characterization of Silent Coupling: Entropy-Enthalpy Compensation in Allostery.Biophysical journal · 2020Article
- Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.Neuropharmacology · 2020Review
- In Silico Modeling of the α7 Nicotinic Acetylcholine Receptor: New Pharmacological Challenges Associated with Multiple Modes of Signaling.Mini reviews in medicinal chemistry · 2020Review
- Impact of modulation of the α7 nicotinic acetylcholine receptor on nicotine reward in the mouse conditioned place preference test.Psychopharmacology · 2019Article
- Allosteric Agonism ofMolecular pharmacology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The α7 nicotinic acetylcholine receptor (nAChR) is a target for control of inflammation-related phenomena via compounds that are able to selectively induce desensitized states of the receptor. Compounds that selectively desensitize, without facilitating significant channel activation, are termed 'silent agonists' because they can be discriminated from antagonists by the currents evoked with co-application with type II positive allosteric modulators (PAMs). One example is N,N-diethyl-N'-phenyl-piperazine (diEPP) (J. Pharm. Exp. Ther.2014, 350, 665). We used Ullmann-type aryl amination to synthesize a panel of 27 compounds related to diEPP by substitutions at the aryl ring and in the linkage between the piperazine and phenyl rings. Two-electrode voltage clamping of the human α7 nAChR expressed in Xenopus oocytes revealed that it was possible to tune the behavior of compounds to show enhanced desensitization without corresponding partial agonist activity such that trifluoromethyl and carboxamide aryl substituents showed 33 to 46-fold larger PAM-dependent net-charge responses, indicating selective partitioning of the ligand receptor complexes into the desensitized state.
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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.