ArticleJournal of medicinal chemistry2017
Structure-Activity Relationship Studies of Pyrimido[5,4-b]indoles as Selective Toll-Like Receptor 4 Ligands.
Article in Journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- Discovery of 9H-pyrimido[4,5-b]indole derivatives as dual RET/TRKA inhibitors.Bioorganic & medicinal chemistry · 2024Article
- Small molecule modulators of immune pattern recognition receptors.RSC chemical biology · 2023Review
- A Triple High Throughput Screening for Extracellular Vesicle Inducing Agents With Immunostimulatory Activity.Frontiers in pharmacology · 2022Article
- Immunomodulatory Response of Toll-like Receptor Ligand-Peptide Conjugates in Food Allergy.ACS chemical biology · 2021Article
- Structure-activity relationship studies in substituted sulfamoyl benzamidothiazoles that prolong NF-κB activation.Bioorganic & medicinal chemistry · 2021Article
- Receptor-Ligand Kinetics Influence the Mechanism of Action of Covalently Linked TLR Ligands.ACS chemical biology · 2021Article
- Nanomedicine-mediated alteration of the pharmacokinetic profile of small molecule cancer immunotherapeutics.Acta pharmacologica Sinica · 2020Review
- Homeostatic and pathogenic roles of GM3 ganglioside molecular species in TLR4 signaling in obesity.The EMBO journal · 2020Article
- A Novel Synthetic Dual Agonistic Liposomal TLR4/7 Adjuvant Promotes Broad Immune Responses in an Influenza Vaccine With Minimal Reactogenicity.Frontiers in immunology · 2020Article
- Recent Advances and Perspectives in Small-molecule TLR Ligands and Their Modulators.ACS medicinal chemistry letters · 2018Article
- Toll-like Receptor Agonist Conjugation: A Chemical Perspective.Bioconjugate chemistry · 2018Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Previous high throughput screening studies led to the discovery of two novel, nonlipid-like chemotypes as Toll-like receptor 4 (TLR4) agonists. One of these chemotypes, the pyrimido[5,4-b]indoles, was explored for structure-activity relationship trends relative to production of TLR4 dependent cytokines/chemokines, resulting in a semioptimized lead (compound 1) that provided a starting point for further optimization studies. In this report, compounds belonging to three areas of structural modification were evaluated for biological activity using murine and human TLR4 reporter cells, primary murine bone marrow derived dendritic cells, and human peripheral blood mononuclear cells. The compounds bearing certain aryl groups at the C8 position, such as phenyl (36) and β-naphthyl (39), had potencies significantly greater than compound 1. Compound 36 displayed human TLR4 agonist activity at submicromolar concentrations. The computational analysis suggests that the improved potency of these C8-aryl derivatives may be the result of additional binding interactions at the interface of the TLR4/myeloid differentiation protein-2 (MD-2) complex.
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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.