{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:16:20Z","timestamp":1777860980539,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100019550","name":"Scheme for Promotion of Academic and Research Collaboration","doi-asserted-by":"publisher","award":["SPARC\/2018\u20102019\/P385\/SL"],"award-info":[{"award-number":["SPARC\/2018\u20102019\/P385\/SL"]}],"id":[{"id":"10.13039\/501100019550","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,4,28]]},"abstract":"<jats:p>\n                    Multiple heterocyclic scaffolds have been found to exhibit agonist or antagonist activity at toll\u2010like receptors (TLRs) with varying degrees of selectivity for the subtypes. TLR7 and 8 agonists are potentially valuable vaccine adjuvants while antagonists show useful activity against autoimmune diseases and cancer. A pyrazolo[1,5\u2010\n                    <jats:italic>c<\/jats:italic>\n                    ]quinazoline based compound\n                    <jats:bold>23<\/jats:bold>\n                    , an unexplored scaffold in the domain of TLR7\/8, was synthesized by analogy with lead agonists and antagonists from the literature. Compound\n                    <jats:bold>23<\/jats:bold>\n                    exhibited moderate agonist activity for both TLR7 and TLR8. The effect of structural modifications at the C1, C8, C9, and C10 position of the pyrazolo[1,5\u2010\n                    <jats:italic>c<\/jats:italic>\n                    ]quinazoline scaffold on hTLR7\/8 activity was investigated by synthesizing a focused library of compounds. Although none of the compounds had agonist activity, three compounds were found to be dual TLR7\/8 antagonists. These findings add to the existing structure\u2010activity relationship\u00a0knowledge of the tricyclic TLR7\/8 modulators that will aid subsequent discovery and optimization of new drug candidates.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202501053","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:55Z","timestamp":1776816055000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design and Synthesis of New Pyrazolo[1,5\u2010\n                    <i>c<\/i>\n                    ]quinazolin\u20105\u2010amines as Potential TLR7\/8 Modulators"],"prefix":"10.1002","volume":"21","author":[{"given":"Kushvinder","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Chemistry and Centre of Advanced Studies in Chemistry Panjab University  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshikazu","family":"Honda\u2010Okubo","sequence":"additional","affiliation":[{"name":"Vaxine Pty Ltd  Warradale Australia"},{"name":"Australian Respiratory and Sleep Medicine Institute  Bedford Park Australia"},{"name":"National Interdisciplinary Centre of Vaccine Immunotherapeutics and Antimicrobials (NICOVIA) Panjab University  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradeep K.","family":"Das","sequence":"additional","affiliation":[{"name":"Institute of Life Science  Bhubaneswar India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anshuman","family":"Dixit","sequence":"additional","affiliation":[{"name":"Institute of Life Science  Bhubaneswar India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamal Nain","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Centre of Advanced Studies in Chemistry Panjab University  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-6076","authenticated-orcid":false,"given":"David A.","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences Monash University  Parkville Victoria Australia"},{"name":"School of Pharmacy University of Nottingham  Nottingham United\u00a0Kingdom"},{"name":"Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science La Trobe University  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-5245","authenticated-orcid":false,"given":"Nikolai","family":"Petrovsky","sequence":"additional","affiliation":[{"name":"Vaxine Pty Ltd  Warradale Australia"},{"name":"Australian Respiratory and Sleep Medicine Institute  Bedford Park Australia"},{"name":"National Interdisciplinary Centre of Vaccine Immunotherapeutics and Antimicrobials (NICOVIA) Panjab University  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1241-9146","authenticated-orcid":false,"given":"Deepak B.","family":"Salunke","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Centre of Advanced Studies in Chemistry Panjab University  Chandigarh India"},{"name":"National Interdisciplinary Centre of Vaccine Immunotherapeutics and Antimicrobials (NICOVIA) Panjab University  Chandigarh India"},{"name":"Department of Medicinal Chemistry National Institute of Pharmaceutical Education and Research  Mohali India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30942-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2019.1710409"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13020142"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00878"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-022-00436-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01504"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2022.102172"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2022.5371"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2019.02.029"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00923-13"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpp\/rgab063"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2021.105021"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni758"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12791"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00508"},{"key":"e_1_2_9_17_1","first-page":"103","article-title":"Design and Synthesis of Toll like Receptor of Inhibitors Optimizing the Potential Drugs for Autoimmune Diseases","volume":"17","author":"Mathew J.","year":"2020","journal-title":"International Journal of Pharmacy and Pharmaceutical Research Human"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175962"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i19.5808"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1MD00031D"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00300"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100358c"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.02.100"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-014-1127-5"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.06.030"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.3.1259"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2ob26705e"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm500744f"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm400694d"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00411"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00011"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19025-z"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.10.031"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8CC05845H"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja111060q"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.4438"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo990362t"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201900376"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.langmuir.1c01143"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.7b04198"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm051256o"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab294"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202501053","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202501053","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202501053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:37:18Z","timestamp":1777516638000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202501053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":41,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,4,28]]}},"alternative-id":["10.1002\/cmdc.202501053"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202501053","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]},"assertion":[{"value":"2025-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202501053"}}