{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T04:29:20Z","timestamp":1786768160220,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-13-20056"],"award-info":[{"award-number":["25-13-20056"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["25-13-20056"],"award-info":[{"award-number":["25-13-20056"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A light-promoted C\u2013H\/C\u2013H coupling of imidazo[1,2-a]pyridines with 5-(hetero)aryl-1,2,5-oxadiazolo[3,4-b]pyrazines was developed using a heterogeneous oxidative photocatalytic system based on molecular oxygen, nanosized TiO2, and light irradiation. The method provides direct access to C3-heteroarylated imidazo[1,2-a]pyridines under metal-free conditions and expands the synthetic utility of electron-deficient oxadiazolopyrazine partners in the construction of biheteroaryl scaffolds. The synthesized compounds were evaluated computationally using a fully connected convolutional correlation neural network based on multiple-docking energy spectra, which prioritized the series as potential COX-1 and COX-2 ligands. To test this prioritization experimentally, all 18 compounds were screened in fluorometric COX-1 and COX-2 inhibitor assays at 1 \u00b5M. Compound 3f emerged as a strong preliminary COX-1 hit at 1 \u00b5M (86.64 \u00b1 5.18% inhibition), whereas 3h and 3l showed weaker COX-1 inhibition. No compound showed high or moderate COX-2 inhibition at the screening concentration; only weak COX-2 inhibitory signals were observed for several derivatives. Thus, the combined synthetic, computational, and enzymatic data identify compound 3f as the main COX-1-skewed hit in this series and provide a basis for further dose\u2013response, selectivity, and cell-based anti-inflammatory studies. It should also be noted that the COX-1 inhibition assay used ovine COX-1, whereas the computational models were built on human COX-1 and COX-2 structures; this species difference is an additional reason to treat the in silico\u2013experimental comparison as approximate.<\/jats:p>","DOI":"10.3390\/molecules31162830","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:01:35Z","timestamp":1786640495000},"page":"2830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Light-Promoted C\u2013H\/C\u2013H Coupling of Imidazo[1,2-a]pyridines with 5-(Hetero)aryl-1,2,5-oxadiazolo[3,4-b]pyrazines over TiO2 and Experimental\/In Silico Evaluation of COX-1 and COX-2 Inhibitory Activity"],"prefix":"10.3390","volume":"31","author":[{"given":"Maria A.","family":"Trestsova","sequence":"first","affiliation":[{"name":"Department of Organic and Biomolecular Chemistry, Ural Federal University, 28 Mira Street, 620002 Ekaterinburg, Russia"},{"name":"Institute of Organic Synthesis of the Russian Academy of Sciences, 22 S. Kovalevskoy Street, 620066 Ekaterinburg, Russia"},{"name":"Russian-Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin prosp., 454080 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria A.","family":"Andreeva","sequence":"additional","affiliation":[{"name":"Department of Organic and Biomolecular Chemistry, Ural Federal University, 28 Mira Street, 620002 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8782-1308","authenticated-orcid":false,"given":"Mikhail A.","family":"Kiskin","sequence":"additional","affiliation":[{"name":"Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, 31 Leninsky prosp., 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2431-8358","authenticated-orcid":false,"given":"Maria V.","family":"Komelkova","sequence":"additional","affiliation":[{"name":"Russian-Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin prosp., 454080 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8188-5052","authenticated-orcid":false,"given":"Pavel M.","family":"Vassiliev","sequence":"additional","affiliation":[{"name":"Russian-Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin prosp., 454080 Chelyabinsk, Russia"},{"name":"Scientific Center for Innovative Medicines, Volgograd State Medical University, 1 Pavshikh Bortsov Square, 400131 Volgograd, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena. S.","family":"Taran","sequence":"additional","affiliation":[{"name":"Russian-Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin prosp., 454080 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7001-6396","authenticated-orcid":false,"given":"Ludmila A.","family":"Yolshina","sequence":"additional","affiliation":[{"name":"Institute of High-Temperature Electrochemistry, Ural Branch of the Russian Academy of Sciences, 20 Akademicheskaya Street, 620066 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3313-8220","authenticated-orcid":false,"given":"Alexander G.","family":"Kvashnichev","sequence":"additional","affiliation":[{"name":"Institute of High-Temperature Electrochemistry, Ural Branch of the Russian Academy of Sciences, 20 Akademicheskaya Street, 620066 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika A.","family":"Isaeva","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, 106 Pervomaiskaya Street, 620049 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4692-9176","authenticated-orcid":false,"given":"Irina A.","family":"Utepova","sequence":"additional","affiliation":[{"name":"Department of Organic and Biomolecular Chemistry, Ural Federal University, 28 Mira Street, 620002 Ekaterinburg, Russia"},{"name":"Institute of Organic Synthesis of the Russian Academy of Sciences, 22 S. 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