ArticleJournal of medicinal chemistry2010
Structure-activity relationships in human toll-like receptor 7-active imidazoquinoline analogues.
Article in Journal of medicinal chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 147 citations in OpenAlex.
- Chemical adaptation: bridging synthetic chemistry with drug development.Science China. Life sciences · 2026Review
- Review
- Efflux-Enhanced Imidazoquinolines To Exploit Chemoresistance.ACS omega · 2025Article
- Design and Synthesis of Polyphenolic Imidazo[4,5-ACS pharmacology & translational science · 2024Article
- Modularized viromimetic polymer nanoparticle vaccines (VPNVaxs) to elicit durable and effective humoral immune responses.National science review · 2024Article
- Article
- Peptide-Decorated Degradable Polycarbonate Nanogels for Eliciting Antigen-Specific Immune Responses.International journal of molecular sciences · 2023Article
- Efficient Self-Immolative RAFT End Group Modification for Macromolecular Immunodrug Delivery.Biomacromolecules · 2023Article
- Synthesis and immunopharmacological evaluation of novel TLR7 agonistic triazole tethered imidazoquinolines.RSC advances · 2023Article
- Influenza breakthrough infection in vaccinated mice is characterized by non-pathological lung eosinophilia.Frontiers in immunology · 2023Article
- Imidazoquinolines with improved pharmacokinetic properties induce a high IFNα to TNFα ratioFrontiers in immunology · 2023Article
- Silver-Catalyzed Cascade Cyclization of Amino-Molecules (Basel, Switzerland) · 2022Article
- High-Titer Neutralizing Antibodies against the SARS-CoV-2 Delta Variant Induced by Alhydroxyquim-II-Adjuvanted Trimeric Spike Antigens.Microbiology spectrum · 2022Article
- Molecular dynamics simulations reveal the selectivity mechanism of structurally similar agonists to TLR7 and TLR8.PloS one · 2022Article
- Acquired Drug Resistance Enhances Imidazoquinoline Efflux by P-Glycoprotein.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Improving the Adjuvanticity of Small Molecule Immune Potentiators Using Covalently Linked NF-κB Modulators.ACS medicinal chemistry letters · 2021Article
- Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants.Advanced drug delivery reviews · 2021Review
- Structural evolution of toll-like receptor 7/8 agonists from imidazoquinolines to imidazoles.RSC medicinal chemistry · 2021Review
- Squaric Ester-Based, pH-Degradable Nanogels: Modular Nanocarriers for Safe, Systemic Administration of Toll-like Receptor 7/8 Agonistic Immune Modulators.Journal of the American Chemical Society · 2021Article
- Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Engagement of toll-like receptors serve to link innate immune responses with adaptive immunity and can be exploited as powerful vaccine adjuvants for eliciting both primary and anamnestic immune responses. TLR7 agonists are highly immunostimulatory without inducing dominant proinflammatory cytokine responses. A structure-activity study was conducted on the TLR7-agonistic imidazoquinolines, starting with 1-(4-amino-2-((ethylamino)methyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol as a lead. Modifications of the secondary amine of the C2 ethylaminomethylene side chain are poorly tolerated. The 4-amino group must be retained for activity. Replacement of the imidazole ring of the scaffold with triazole or cyclic urea led to complete loss of activity. A systematic exploration of N(1)-benzyl-C2-alkyl substituents showed a very distinct relationship between alkyl length and TLR7-agonistic potency with the optimal compound bearing a C2-n-butyl group. Transposition of the N(1) and C2 substituents led to the identification of an extremely active TLR7-agonistic compound with an EC(50) value of 8.6 nM. The relative potencies in human TLR7-based primary reporter gene assays were paralleled by interferon-alpha induction activities in whole human blood models.
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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.