ArticleJournal of medicinal chemistry2016
Novel Analogues of (R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist Selectivity.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed.
- A Ligand-Triggered Receptor Conformation Enables the Design of Selective Agonists for the Dopamine 3 Receptor (DJACS Au · 2026Article
- Presynaptic and Postsynaptic Mesolimbic Dopamine DBiological psychiatry · 2024Article
- Optical Control of Dopamine D2-like Receptors with Cell-Specific Fast-Relaxing Photoswitches.Journal of the American Chemical Society · 2023Article
- Dopamine DJournal of medicinal chemistry · 2023Article
- Identification of Novel Dopamine DMolecules (Basel, Switzerland) · 2022Article
- Dopamine and Dopamine-Related Ligands Can Bind Not Only to Dopamine Receptors.Life (Basel, Switzerland) · 2022Review
- Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis fromRSC medicinal chemistry · 2021Article
- Chiral Cyclic Aliphatic Linkers as Building Blocks for Selective Dopamine DJournal of medicinal chemistry · 2021Article
- Structure Activity Relationships for a Series of Eticlopride-Based Dopamine DJournal of medicinal chemistry · 2021Article
- Cell specific photoswitchable agonist for reversible control of endogenous dopamine receptors.Nature communications · 2021Article
- Chirality of Novel Bitopic Agonists Determines Unique Pharmacology at the Dopamine D3 Receptor.Biomolecules · 2021Article
- Discovery, Optimization, and Characterization of ML417: A Novel and Highly Selective DJournal of medicinal chemistry · 2020Article
- 2016 Philip S. Portoghese Medicinal Chemistry Lectureship: Designing Bivalent or Bitopic Molecules for G-Protein Coupled Receptors. The Whole Is Greater Than the Sum of Its Parts.Journal of medicinal chemistry · 2020Article
- Molecular Determinants of the Intrinsic Efficacy of the Antipsychotic Aripiprazole.ACS chemical biology · 2019Article
- The Significance of Chirality in Drug Design and Synthesis of Bitopic Ligands as DJournal of medicinal chemistry · 2019Article
- Dopamine DJournal of medicinal chemistry · 2019Article
- Novel and Potent Dopamine DACS pharmacology & translational science · 2019Article
- Advances and challenges in the search for DCellular signalling · 2018Review
- β-Hydroxy-tetrahydroquinolines from Quinolines Using Chloroborane: Synthesis of the Peptidomimetic FISLE-412.Chemistry (Weinheim an der Bergstrasse, Germany) · 2017Article
- Novel Bivalent Ligands Based on the Sumanirole Pharmacophore Reveal Dopamine DJournal of medicinal chemistry · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
Novel 1-, 5-, and 8-substituted analogues of sumanirole (1), a dopamine D2/D3 receptor (D2R/D3R) agonist, were synthesized. Binding affinities at both D2R and D3R were higher when determined in competition with the agonist radioligand [(3)H]7-hydroxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT) than with the antagonist radioligand [(3)H]N-methylspiperone. Although 1 was confirmed as a D2R-preferential agonist, its selectivity in binding and functional studies was lower than previously reported. All analogues were determined to be D2R/D3R agonists in both GoBRET and mitogenesis functional assays. Loss of efficacy was detected for the N-1-substituted analogues at D3R. In contrast, the N-5-alkyl-substituted analogues, and notably the n-butyl-arylamides (22b and 22c), all showed improved affinity at D2R over 1 with neither a loss of efficacy nor an increase in selectivity. Computational modeling provided a structural basis for the D2R selectivity of 1, illustrating how subtle differences in the highly homologous orthosteric binding site (OBS) differentially affect D2R/D3R affinity and functional efficacy.
Indexed as
Identifiers
What OpenQuestion holds
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.