{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["DeYoung EG"],"funding":["National Institute of Allergy and Infectious Diseases","NIAID NIH HHS","NCI NIH HHS","National Institute of General Medical Sciences","NIGMS NIH HHS","Heidelberg Pharma AG"],"pagination":["1358-1368"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10577892"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(10)"],"pubmed_abstract":["TLR7 agonists have significant therapeutic potential in a variety of oncology and autoimmune applications. We recently reported a potent TLR7 selective agonist <b>1</b> that could be delivered by antibody-drug conjugate (ADC) technology to elicit potent anticancer activity. Herein we report synthetic chemistry and structure-activity relationship studies to develop TLR7 agonists with improved potency for next-generation ADC efforts. We found that the addition of hydrophobic acyl tails to parent compound <b>1</b> generally resulted in retained or improved TLR7 agonist activity without sacrificing the permeability or the selectivity over TLR8. In contrast, the addition of a simple alkyl tail at the same position resulted in a dramatic loss in potency. Molecular modeling was performed to provi"],"journal":["ACS medicinal chemistry letters"],"pubmed_title":["Synthesis and Optimization of 1-Substituted Imidazo[4,5-<i>c</i>]quinoline TLR7 Agonists."],"pmcid":["PMC10577892"],"funding_grant_id":["R01GM140026","R01 GM140026","R15 AI149755","R15 CA227747","1R15AI149755-01"],"pubmed_authors":["Tumey LN","Handel JP","Gillen Miller JT","DeYoung EG","Reddy MM","Fang S","Howe JM","Wheeler DR"],"additional_accession":[]},"is_claimable":false,"name":"Synthesis and Optimization of 1-Substituted Imidazo[4,5-<i>c</i>]quinoline TLR7 Agonists.","description":"TLR7 agonists have significant therapeutic potential in a variety of oncology and autoimmune applications. We recently reported a potent TLR7 selective agonist <b>1</b> that could be delivered by antibody-drug conjugate (ADC) technology to elicit potent anticancer activity. Herein we report synthetic chemistry and structure-activity relationship studies to develop TLR7 agonists with improved potency for next-generation ADC efforts. We found that the addition of hydrophobic acyl tails to parent compound <b>1</b> generally resulted in retained or improved TLR7 agonist activity without sacrificing the permeability or the selectivity over TLR8. In contrast, the addition of a simple alkyl tail at the same position resulted in a dramatic loss in potency. Molecular modeling was performed to provi","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Oct","modification":"2026-06-03T03:48:16.091Z","creation":"2025-04-06T13:21:03.977Z"},"accession":"S-EPMC10577892","cross_references":{"pubmed":["37849530"],"doi":["10.1021/acsmedchemlett.3c00260"]}}