ArticleJournal of medicinal chemistry2012
Design, synthesis, and structure-activity relationships of highly potent 5-HT₃ receptor ligands.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- 5-HTCurrent neuropharmacology · 2021Pooled it
- Indole-containing pharmaceuticals: targets, pharmacological activities, and SAR studies.RSC medicinal chemistry · 2024Review
- Structure-Guided Design ofInternational journal of molecular sciences · 2023Article
- Mono- and Diamination of 4,6-Dichloropyrimidine, 2,6-Dichloropyrazine and 1,3-Dichloroisoquinoline with Adamantane-Containing Amines.Molecules (Basel, Switzerland) · 2021Article
- Discovery of fragments inducing conformational effects in dynamic proteins using a second-harmonic generation biosensor.RSC advances · 2021Article
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Article
- Histone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti-MedChemComm · 2017Article
- A fluorescent approach for identifying P2X1 ligands.Neuropharmacology · 2015Article
- The binding characteristics and orientation of a novel radioligand with distinct properties at 5-HT3A and 5-HT3AB receptors.Neuropharmacology · 2014Article
- A single channel mutation alters agonist efficacy at 5-HT3A and 5-HT3AB receptors.British journal of pharmacology · 2013Article
- Discriminating between 5-HT₃A and 5-HT₃AB receptors.British journal of pharmacology · 2013Review
- Structure-activity relationships of quinoxaline-based 5-HT3A and 5-HT3AB receptor-selective ligands.ChemMedChem · 2013Article
- Identification, design and bio-evaluation of novel Hsp90 inhibitors by ligand-based virtual screening.PloS one · 2013Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The 5-HT₃ receptor, a pentameric ligand-gated ion channel (pLGIC), is an important therapeutic target. During a recent fragment screen, 6-chloro-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine (1) was identified as a 5-HT₃ hit fragment. Here we describe the synthesis and structure-activity relationships (SAR) of a series of (iso)quinoline and quinazoline compounds that were synthesized and screened for 5-HT₃ R affinity using a [³H]granisetron displacement assay. These studies resulted in the discovery of several high affinity ligands of which compound 22 showed the highest affinity (pK(i) > 10) for the 5-HT₃ receptor. The observed SAR is in agreement with established pharmacophore models for 5-HT₃ ligands and is used for ligand-receptor binding mode prediction using homology modeling and in silico docking approaches.
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