{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:48:33Z","timestamp":1792003713333,"version":"4.4.0"},"reference-count":63,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["124020500044 and the"],"award-info":[{"award-number":["124020500044 and the"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017638","name":"Ministry of Health of the Russian Federation","doi-asserted-by":"publisher","award":["124021500036\u20106"],"award-info":[{"award-number":["124021500036\u20106"]}],"id":[{"id":"10.13039\/501100017638","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":[[2026,10,14]]},"abstract":"<jats:p>\n                    Small molecules that simultaneously suppress nitric oxide (NO) and interleukin\u20116 (IL\u20116) offer a strategy to alleviate pathological inflammation. Building on our previous work with aryl\u2011substituted azaheterocycles, we synthesized 33 new pyrimidine and azolopyrimidine derivatives bearing amino, amide, hydroxyl, or halide groups to enhance hydrogen\u2011bonding capacity and improve inhibitory activity against both mediators. Screening in C57BL\/6J mouse peritoneal macrophages identified nine compounds that markedly inhibited NO production at 50\u2009\u00b5M. Two leads\u2014triazolo[1,5\u2011a]pyrimidine 12bc and dihydropyrimidine carboxamide 7a\u2014emerged as potent dual inhibitors. Compound 7a showed IC\n                    <jats:sub>50<\/jats:sub>\n                    values of\u00a00.47\u202f\u00b5M (NO) and 0.1\u2009\u00b5M (IL\u20116); 12bc gave 8.66\u2009\u00b5M (NO) and 0.85\u2009\u00b5M (IL\u20116), both with acceptable cytotoxicity. In human PBMC\u2011derived monocytes, both compounds dose\u2011dependently suppressed LPS\u2011induced IL\u20116 secretion; 12bc was slightly more potent, reducing IL\u20116 to near\u2011baseline at 100\u2009\u00b5M, comparable to dexamethasone. In an LPS\/ATP pyroptosis model, they protected monocytes from inflammatory death, with 12bc nearly restoring normal cell morphology. Docking studies into mouse iNOS and IL\u20116 suggested plausible binding modes and structure\u2013activity relationships. These (azolo)pyrimidine scaffolds represent promising leads for safe, dual\u2011acting anti\u2011inflammatory agents.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70485","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:28:56Z","timestamp":1791181736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel (Azolo)Pyrimidine Derivatives as Dual Modulators of NO and IL\u20106 in Murine Macrophages and Human Monocytes"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3304-6553","authenticated-orcid":false,"given":"Irina G.","family":"Ovchinnikova","sequence":"first","affiliation":[{"name":"I. Ya. Postovsky Institute of Organic Synthesis Ural Branch of the Russian Academy of Sciences  Ekaterinburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9355-283X","authenticated-orcid":false,"given":"Olga V.","family":"Fedorova","sequence":"additional","affiliation":[{"name":"I. Ya. Postovsky Institute of Organic Synthesis Ural Branch of the Russian Academy of Sciences  Ekaterinburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4610-3617","authenticated-orcid":false,"given":"Nikolay A.","family":"Rasputin","sequence":"additional","affiliation":[{"name":"I. Ya. Postovsky Institute of Organic Synthesis Ural Branch of the Russian Academy of Sciences  Ekaterinburg Russia"},{"name":"Technology Scaling and Implementation Laboratory Ural Federal University Named after the First President of Russia B. N. Yeltsin  Ekaterinburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8814-5180","authenticated-orcid":false,"given":"Grigory A.","family":"Kim","sequence":"additional","affiliation":[{"name":"I. Ya. Postovsky Institute of Organic Synthesis Ural Branch of the Russian Academy of Sciences  Ekaterinburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6298-3733","authenticated-orcid":false,"given":"Elena S.","family":"Filatova","sequence":"additional","affiliation":[{"name":"I. Ya. Postovsky Institute of Organic Synthesis Ural Branch of the Russian Academy of Sciences  Ekaterinburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina K.","family":"Titova","sequence":"additional","affiliation":[{"name":"I. Ya. Postovsky Institute of Organic Synthesis Ural Branch of the Russian Academy of Sciences  Ekaterinburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9645-3324","authenticated-orcid":false,"given":"Denis A.","family":"Babkov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Bioinformatics Scientific Center for Innovative Drugs Volgograd State Medical University  Volgograd Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V.","family":"Sokolova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Bioinformatics Scientific Center for Innovative Drugs Volgograd State Medical University  Volgograd Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey V.","family":"Lukyanov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Bioinformatics Scientific Center for Innovative Drugs Volgograd State Medical University  Volgograd Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1593-4549","authenticated-orcid":false,"given":"Roman D.","family":"Danilov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Bioinformatics Scientific Center for Innovative Drugs Volgograd State Medical University  Volgograd Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennady L.","family":"Rusinov","sequence":"additional","affiliation":[{"name":"I. Ya. Postovsky Institute of Organic Synthesis Ural Branch of the Russian Academy of Sciences  Ekaterinburg Russia"},{"name":"Department of Technology &amp; Organic Synthesis Ural Federal University Named After the First President of Russia B. N. Yeltsin  Ekaterinburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Spasov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Bioinformatics Scientific Center for Innovative Drugs Volgograd State Medical University  Volgograd Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egor V.","family":"Verbitskiy","sequence":"additional","affiliation":[{"name":"I. Ya. Postovsky Institute of Organic Synthesis Ural Branch of the Russian Academy of Sciences  Ekaterinburg Russia"},{"name":"Department of Organic and Biomolecular Chemistry Ural Federal University Named after the First President of Russia B. N. Yeltsin  Ekaterinburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery N.","family":"Charushin","sequence":"additional","affiliation":[{"name":"I. Ya. Postovsky Institute of Organic Synthesis Ural Branch of the Russian Academy of Sciences  Ekaterinburg Russia"},{"name":"Department of Organic and Biomolecular Chemistry Ural Federal University Named after the First President of Russia B. N. Yeltsin  Ekaterinburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00626"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1289194"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873\u20103468.14033"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.03.006"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.35.22201"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1411569"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2020.115327"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6305"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm401144z"},{"key":"e_1_2_10_11_1","volume-title":"Reactive Oxygen Species, Handbook of Experimental Pharmacology","author":"Dao V. T.","year":"2020"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.1c00276"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25158486"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.181"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2023.04.007"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042\u20107158.2010.01236.x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2022.2103735"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1070\/RC2010v079n08ABEH004116"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.4226"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044\u2010020\u201002609\u20101"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.10.073"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1070\/RCR4586"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0RA10657G"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115848"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105272"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2024.1387923"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201700175"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.4.1506"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm061319i"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01146"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2019.1618291"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202400238"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.5c00683"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28020741"},{"key":"e_1_2_10_35_1","unstructured":"Supporting Information (containing experimental procedures characterization data copies of NMR spectra additional biological assay results and molecular docking analys."},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202101076"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2018.51.6.064"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.3.1184.1184"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117634"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.323"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1001\u2010907"},{"key":"e_1_2_10_42_1","doi-asserted-by":"crossref","unstructured":"PDB ID: 1DWW Murine Inducible Nitric Oxide Synthase Oxygenase Dimer N\u2010Hydroxyarginine and Dihydrobiopterin. Classification: Oxidoreductase\/Transferase Organism(s): Mus Musculus Expression System: Escherichia Coli https:\/\/doi.org\/10.2210\/pdb1DWW\/pdb.","DOI":"10.2210\/pdb1dww\/pdb"},{"key":"e_1_2_10_43_1","doi-asserted-by":"crossref","unstructured":"PDB ID: 2L3Y Solution Structure of Mouse IL\u20106 Interleukin\u20106 Organism(s): Mus Musculus Expression System: Escherichia Coli https:\/\/doi.org\/10.2210\/pdb2L3Y\/pdb.","DOI":"10.2210\/pdb2l3y\/pdb"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.405597"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi992409a"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570180816666190222154457"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.115"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181251298"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0079\u20106107(84)90007\u20105"},{"key":"e_1_2_10_50_1","unstructured":"E.Martz Help Index & Glossary for Protein Explorer http:\/\/www.umass.edu\/microbio\/chime\/pe_beta\/pe\/protexpl\/igloss.htm."},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.01.034"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083901"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.026"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)65605\u20102"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0266632"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.5.989"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242115581"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1401s83"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889808042726"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053229614024218"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053273314026370"},{"key":"e_1_2_10_62_1","unstructured":"Deposition numbers 2486381 (for 12ba) 2486380 (for12bc) and 2486360 (for12bf) contain the supplementary crystallographic data for this paper These Data Are provided Free of Charge by the Joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures Service."},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70485","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.70485","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70485","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:08:36Z","timestamp":1792001316000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.70485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,4]]},"references-count":63,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,10,14]]}},"alternative-id":["10.1002\/cmdc.70485"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.70485","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,4]]},"assertion":[{"value":"2026-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70485"}}