{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T21:56:23Z","timestamp":1793915783189,"version":"4.8.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X014118\/1"],"award-info":[{"award-number":["MR\/X014118\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X014118\/1"],"award-info":[{"award-number":["MR\/X014118\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X014118\/1"],"award-info":[{"award-number":["MR\/X014118\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X014118\/1"],"award-info":[{"award-number":["MR\/X014118\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X014118\/1"],"award-info":[{"award-number":["MR\/X014118\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X014118\/1"],"award-info":[{"award-number":["MR\/X014118\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"RCUK | Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/X028178\/1"],"award-info":[{"award-number":["EP\/X028178\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"RCUK | Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/V028995\/1"],"award-info":[{"award-number":["EP\/V028995\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat. Chem."],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Although naphthalene motifs are frequently encountered in drugs and lead compounds, their flat,\n                    <jats:italic>sp<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    -rich nature and susceptibility to cytochrome P450-mediated metabolism often limit their developability. Here we report the study of derivatizable aryl-fused bicyclo[3.1.1]heptanes (BCHeps) as\n                    <jats:italic>sp<\/jats:italic>\n                    <jats:sup>3<\/jats:sup>\n                    -rich bioisosteric replacements for naphthalene and other fused bicyclic (hetero)aromatics, including underrepresented \u03b2-naphthyl units. The BCHeps were efficiently accessed via an intramolecular crossed [2+2] photocycloaddition enabled by visible light energy transfer and subsequently diversified to provide a range of different scaffolds. Here we show that the incorporation of BCHep-based naphthyl isosteres into the AhR antagonist ezutromid preserves key geometric exit vectors while reducing the fraction of\n                    <jats:italic>sp<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    carbon atoms. Importantly, these analogues retain biological activity and display improved metabolic stability towards CYP1A-mediated metabolism. Solid-state structures, cellular assays and microsomal studies confirm that BCHep substitution mitigates reactive metabolite formation, validating aryl-fused BCHeps as true bioisosteric replacements for\n                    <jats:italic>meta<\/jats:italic>\n                    -substituted arenes and 2-naphthalenes.\n                  <\/jats:p>","DOI":"10.1038\/s41557-026-02129-2","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:04:12Z","timestamp":1778058252000},"page":"1075-1081","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synthesis of aryl-fused bicyclo[3.1.1]heptanes and validation as naphthyl bioisosteres"],"prefix":"10.1038","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4056-6909","authenticated-orcid":false,"given":"Aidan","family":"Kerckhoffs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7504-7439","authenticated-orcid":false,"given":"Maud","family":"Tregear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2465-3949","authenticated-orcid":false,"given":"Pol","family":"Hern\u00e1ndez-Llad\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3608-2031","authenticated-orcid":false,"given":"Massimiliano","family":"Runfola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1418-6560","authenticated-orcid":false,"given":"Holly","family":"Shearsmith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0375-3621","authenticated-orcid":false,"given":"Marc","family":"Panosetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Squire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Moir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1683-2066","authenticated-orcid":false,"given":"Kirsten E.","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Duarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8807-8520","authenticated-orcid":false,"given":"Kay E.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3610-9369","authenticated-orcid":false,"given":"Angela J.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"2129_CR1","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.ejmech.2018.10.018","volume":"161","author":"S Makar","year":"2019","unstructured":"Makar, S., Saha, T. & Singh, S. K. Naphthalene, a versatile platform in medicinal chemistry: sky-high perspective. Eur. J. Med. Chem. 161, 252\u2013276 (2019).","journal-title":"Eur. J. Med. Chem."},{"key":"2129_CR2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/annotation\/900a5247-7d03-4686-a544-5f7f64c0aac5","volume":"6","author":"K Davies","year":"2011","unstructured":"Davies, K. et al. Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse. PLoS ONE 6, 1\u201310 (2011).","journal-title":"PLoS ONE"},{"key":"2129_CR3","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1007\/s00044-023-03051-9","volume":"32","author":"A Saeed","year":"2023","unstructured":"Saeed, A. et al. Design, synthesis, biochemical and in silico characterization of novel naphthalene\u2013thiourea conjugates as potential and selective inhibitors of alkaline phosphatase. Med. Chem. Res. 32, 1077\u20131086 (2023).","journal-title":"Med. Chem. Res."},{"key":"2129_CR4","doi-asserted-by":"publisher","first-page":"6525","DOI":"10.1021\/ja01025a058","volume":"90","author":"D Jerina","year":"1968","unstructured":"Jerina, D. et al. The role of arene oxide\u2013oxepin systems in the metabolism of aromatic substrates. III. Formation of 1,2-naphthalene oxide from naphthalene by liver microsomes. J. Am. Chem. Soc. 90, 6525\u20136527 (1968).","journal-title":"J. Am. Chem. Soc."},{"key":"2129_CR5","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0009-2797(89)90031-8","volume":"71","author":"M Buonarati","year":"1989","unstructured":"Buonarati, M., Morin, D., Plopper, C. & Buckpitt, A. Glutathione depletion and cytotoxicity by naphthalene 1,2-oxide in isolated hepatocytes. Chem. Biol. Interact. 71, 147\u2013165 (1989).","journal-title":"Chem. Biol. Interact."},{"key":"2129_CR6","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1021\/bi00803a019","volume":"9","author":"D Jerina","year":"1970","unstructured":"Jerina, D. et al. 1,2-Naphthalene oxide as an intermediate in the microsomal hydroxylation of naphthalene. V. Biochem. 9, 147\u2013156 (1970).","journal-title":"V. Biochem."},{"key":"2129_CR7","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1124\/dmd.105.005785","volume":"34","author":"MC Taehyeon","year":"2006","unstructured":"Taehyeon, M. C., Randy, L. R. & Ernest, H. In vitro metabolism of naphthalene by human liver microsomal cytochrome P450 enzymes. Drug Metab. Dispos. 34, 176\u2013183 (2006).","journal-title":"Drug Metab. Dispos."},{"key":"2129_CR8","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.apsb.2012.02.001","volume":"2","author":"L Hu","year":"2012","unstructured":"Hu, L., Paul Fawcett, J. & Gu, J. Protein target discovery of drug and its reactive intermediate metabolite by using proteomic strategy. Acta Pharm. Sin. B 2, 126\u2013136 (2012).","journal-title":"Acta Pharm. Sin. B"},{"key":"2129_CR9","doi-asserted-by":"publisher","first-page":"8011","DOI":"10.1021\/acs.jmedchem.5b00824","volume":"58","author":"P Risch","year":"2015","unstructured":"Risch, P., Pfeifer, T., Segrestaa, J., Fretz, H. & Pothier, J. Verification of the major metabolic oxidation path for the naphthoyl group in chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) antagonist 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid (setipiprant\/ACT-129968). J. Med. Chem. 58, 8011\u20138035 (2015).","journal-title":"J. Med. Chem."},{"key":"2129_CR10","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1021\/acs.jmedchem.9b01547","volume":"63","author":"M Chatzopoulou","year":"2020","unstructured":"Chatzopoulou, M. et al. Isolation, structural identification, synthesis, and pharmacological profiling of 1,2-trans-dihydro-1,2-diol metabolites of the utrophin modulator ezutromid. J. Med. Chem. 63, 2547\u20132556 (2020).","journal-title":"J. Med. Chem."},{"key":"2129_CR11","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/S0090-9556(24)15022-2","volume":"27","author":"EMV Alison","year":"1999","unstructured":"Alison, E. M. V. et al. Multiple cytochrome P-450s involved in the metabolism of terbinafine suggest a limited potential for drug\u2013drug interactions. Drug Metab. Dispos. 27, 1029\u20131038 (1999).","journal-title":"Drug Metab. Dispos."},{"key":"2129_CR12","doi-asserted-by":"publisher","first-page":"3493","DOI":"10.3390\/molecules25153493","volume":"25","author":"MJ Buskes","year":"2020","unstructured":"Buskes, M. J. & Blanco, M. J. Impact of cross-coupling reactions in drug discovery and development. Molecules 25, 3493 (2020).","journal-title":"Molecules"},{"key":"2129_CR13","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1016\/j.bmcl.2008.02.006","volume":"18","author":"G Chandrasena","year":"2008","unstructured":"Chandrasena, G. et al. Identification and optimization of a novel series of [2.2.1]-oxabicyclo imide-based androgen receptor antagonists. Bioorg. Med. Chem. Lett. 18, 1910\u20131915 (2008).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2129_CR14","doi-asserted-by":"publisher","first-page":"9776","DOI":"10.1021\/jm5012808","volume":"57","author":"S Hadida","year":"2014","unstructured":"Hadida, S. et al. Discovery of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, ivacaftor), a potent and orally bioavailable CFTR potentiator. J. Med. Chem. 57, 9776\u20139795 (2014).","journal-title":"J. Med. Chem."},{"key":"2129_CR15","doi-asserted-by":"publisher","first-page":"7880","DOI":"10.1021\/acs.jmedchem.0c00807","volume":"63","author":"A Babbs","year":"2020","unstructured":"Babbs, A. et al. 2-Arylbenzo[d]oxazole phosphinate esters as second-generation modulators of utrophin for the treatment of duchenne muscular dystrophy. J. Med. Chem. 63, 7880\u20137891 (2020).","journal-title":"J. Med. Chem."},{"key":"2129_CR16","doi-asserted-by":"publisher","first-page":"8029","DOI":"10.1021\/acs.jmedchem.8b01133","volume":"61","author":"BG Richardson","year":"2018","unstructured":"Richardson, B. G. et al. Replacement of a naphthalene scaffold in kelch-like ECH-associated protein 1 (KEAP1)\/nuclear factor (erythroid-derived 2)-like 2 (NRF2) inhibitors. J. Med. Chem. 61, 8029\u20138047 (2018).","journal-title":"J. Med. Chem."},{"key":"2129_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28111-3","volume":"13","author":"Q Wang","year":"2022","unstructured":"Wang, Q. et al. Structural basis of the ligand binding and signaling mechanism of melatonin receptors. Nat. Commun. 13, 454 (2022).","journal-title":"Nat. Commun."},{"key":"2129_CR18","doi-asserted-by":"publisher","first-page":"7434","DOI":"10.1016\/j.bmc.2006.07.024","volume":"14","author":"S Chackal-Catoen","year":"2006","unstructured":"Chackal-Catoen, S. et al. Dicationic DNA-targeted antiprotozoal agents: naphthalene replacement of benzimidazole. Bioorg. Med. Chem. 14, 7434\u20137445 (2006).","journal-title":"Bioorg. Med. Chem."},{"key":"2129_CR19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1021\/jm00105a011","volume":"34","author":"P Nussbaumer","year":"1991","unstructured":"Nussbaumer, P., Petranyi, G. & Stuetz, A. Synthesis and structure-activity relationships of benzo[b]thienylallylamine antimycotics. J. Med. Chem. 34, 65\u201373 (1991).","journal-title":"J. Med. Chem."},{"key":"2129_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1590\/s2175-97902019000418124","volume":"56","author":"H Shirinzadeh","year":"2020","unstructured":"Shirinzadeh, H. et al. Bioisosteric modification on melatonin: synthesis of new naphthalene derivatives, in vitro antioxidant activity and cytotoxicity studies. Braz. J. Pharm. Sci. 56, 1\u201311 (2020).","journal-title":"Braz. J. Pharm. Sci."},{"key":"2129_CR21","doi-asserted-by":"publisher","first-page":"9287","DOI":"10.1021\/acs.jmedchem.5b01088","volume":"58","author":"FJR Rombouts","year":"2015","unstructured":"Rombouts, F. J. R., Tovar, F., Austin, N., Tresadern, G. & Trabanco, A. A. Benzazaborinines as novel bioisosteric replacements of naphthalene: propranolol as an example. J. Med. Chem. 58, 9287\u20139295 (2015).","journal-title":"J. Med. Chem."},{"key":"2129_CR22","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1016\/j.bmc.2018.02.026","volume":"26","author":"HS Sutherland","year":"2018","unstructured":"Sutherland, H. S. et al. Structure\u2013activity relationships for analogs of the tuberculosis drug bedaquiline with the naphthalene unit replaced by bicyclic heterocycles. Bioorg. Med. Chem. 26, 1797\u20131809 (2018).","journal-title":"Bioorg. Med. Chem."},{"key":"2129_CR23","doi-asserted-by":"publisher","first-page":"5061","DOI":"10.1021\/jm100112j","volume":"53","author":"C Bissantz","year":"2010","unstructured":"Bissantz, C., Kuhn, B. & Stahl, M. A medicinal chemist\u2019s guide to molecular interactions. J. Med. Chem. 53, 5061\u20135084 (2010).","journal-title":"J. Med. Chem."},{"key":"2129_CR24","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1016\/j.drudis.2020.07.017","volume":"25","author":"W Wei","year":"2020","unstructured":"Wei, W., Cherukupalli, S., Jing, L., Liu, X. & Zhan, P. Fsp3: a new parameter for drug-likeness. Drug Discov. Today 25, 1839\u20131845 (2020).","journal-title":"Drug Discov. Today"},{"key":"2129_CR25","doi-asserted-by":"publisher","first-page":"14046","DOI":"10.1021\/acs.jmedchem.1c01215","volume":"64","author":"MAM Subbaiah","year":"2021","unstructured":"Subbaiah, M. A. M. & Meanwell, N. A. Bioisosteres of the phenyl ring: recent strategic applications in lead optimization and drug design. J. Med. Chem. 64, 14046\u201314128 (2021).","journal-title":"J. Med. Chem."},{"key":"2129_CR26","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/s41586-020-2060-z","volume":"580","author":"X Zhang","year":"2020","unstructured":"Zhang, X. et al. Copper-mediated synthesis of drug-like bicyclopentanes. Nature 580, 220\u2013226 (2020).","journal-title":"Nature"},{"key":"2129_CR27","doi-asserted-by":"publisher","first-page":"3414","DOI":"10.1021\/jm300094u","volume":"55","author":"AF Stepan","year":"2012","unstructured":"Stepan, A. F. et al. Application of the bicyclo[1.1.1]pentane motif as a nonclassical phenyl ring bioisostere in the design of a potent and orally active \u03b3-secretase inhibitor. J. Med. Chem. 55, 3414\u20133424 (2012).","journal-title":"J. Med. Chem."},{"key":"2129_CR28","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/s41586-022-05290-z","volume":"611","author":"N Frank","year":"2022","unstructured":"Frank, N. et al. Synthesis of meta-substituted arene bioisosteres from [3.1.1]propellane. Nature 611, 721\u2013726 (2022).","journal-title":"Nature"},{"key":"2129_CR29","unstructured":"Josien, H. B. et al. Bridged and fused antidiabetic compounds. US Patent US20140038970A1 (2014)."},{"key":"2129_CR30","doi-asserted-by":"publisher","first-page":"9807","DOI":"10.1021\/jacs.7b05277","volume":"139","author":"J Zhao","year":"2017","unstructured":"Zhao, J. et al. Intramolecular crossed [2+2] photocycloaddition through visible light-induced energy transfer. J. Am. Chem. Soc. 139, 9807\u20139810 (2017).","journal-title":"J. Am. Chem. Soc."},{"key":"2129_CR31","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.chempr.2020.07.010","volume":"6","author":"F Glorius","year":"2020","unstructured":"Glorius, F. & Strieth-Kalthoff, F. Triplet energy transfer photocatalysis: unlocking the next level. Chem 6, 1888\u20131903 (2020).","journal-title":"Chem"},{"key":"2129_CR32","doi-asserted-by":"publisher","first-page":"20109","DOI":"10.1021\/jacs.2c09690","volume":"144","author":"ZC Girvin","year":"2022","unstructured":"Girvin, Z. C. et al. Asymmetric photochemical [2+2]-cycloaddition of acyclic vinylpyridines through ternary complex formation and an uncontrolled sensitization mechanism. J. Am. Chem. Soc. 144, 20109\u201320117 (2022).","journal-title":"J. Am. Chem. Soc."},{"key":"2129_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12844-9","volume":"10","author":"W Xu","year":"2019","unstructured":"Xu, W., Wang, W., Liu, T., Xie, J. & Zhu, C. Late-stage trifluoromethylthiolation of benzylic C\u2013H bonds. Nat. Commun. 10, 4867 (2019).","journal-title":"Nat. Commun."},{"key":"2129_CR34","doi-asserted-by":"publisher","first-page":"322","DOI":"10.2741\/e737","volume":"7","author":"K Chung","year":"2015","unstructured":"Chung, K. Occurrence, uses and carcinogenicity of arylamines. Front. Biosci. 7, 322\u2013345 (2015).","journal-title":"Front. Biosci."},{"key":"2129_CR35","doi-asserted-by":"crossref","unstructured":"Glorius, F. et al. Catalytic access to alkyl bromides, chlorides and iodides via visible light-promoted decarboxylative halogenation. Chem. Eur. J. 22, 9971\u20139974 (2016).","DOI":"10.1002\/chem.201602251"},{"key":"2129_CR36","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1002\/chem.201605640","volume":"23","author":"W-M Cheng","year":"2017","unstructured":"Cheng, W.-M., Shang, R., Fu, M.-C. & Fu, Y. Photoredox-catalysed decarboxylative alkylation of N-heteroarenes with N-(acyloxy)phthalimides. Chem. Eur. J. 23, 2537\u20132541 (2017).","journal-title":"Chem. Eur. J."},{"key":"2129_CR37","doi-asserted-by":"publisher","first-page":"14279","DOI":"10.1080\/07391102.2021.1997818","volume":"40","author":"S Khatun","year":"2022","unstructured":"Khatun, S., Singh, A., Bader, G. N. & Sofi, F. A. Imidazopyridine, a promising scaffold with potential medicinal applications and structural activity relationship (SAR): recent advances. J. Biomol. Struct. Dyn. 40, 14279\u201314302 (2022).","journal-title":"J. Biomol. Struct. Dyn."},{"key":"2129_CR38","doi-asserted-by":"publisher","first-page":"3241","DOI":"10.1021\/jm200135z","volume":"54","author":"DR Chancellor","year":"2011","unstructured":"Chancellor, D. R. et al. Discovery of 2-arylbenzoxazoles as upregulators of utrophin production for the treatment of Duchenne muscular dystrophy. J. Med. Chem. 54, 3241\u20133250 (2011).","journal-title":"J. Med. Chem."},{"key":"2129_CR39","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1080\/21678707.2018.1438261","volume":"6","author":"S Guiraud","year":"2018","unstructured":"Guiraud, S., Roblin, D. & Kay, D. E. The potential of utrophin modulators for the treatment of Duchenne muscular dystrophy. Expert Opin. Orphan Drugs 6, 179\u2013192 (2018).","journal-title":"Expert Opin. Orphan Drugs"},{"key":"2129_CR40","doi-asserted-by":"publisher","first-page":"2420","DOI":"10.1002\/anie.201912392","volume":"59","author":"IVL Wilkinson","year":"2020","unstructured":"Wilkinson, I. V. L. et al. Chemical proteomics and phenotypic profiling identifies the aryl hydrocarbon receptor as a molecular target of the utrophin modulator ezutromid. Angew. Chem. Int. Ed. 59, 2420\u20132428 (2020).","journal-title":"Angew. Chem. Int. Ed."},{"key":"2129_CR41","first-page":"1","volume":"36","author":"A Lu","year":"2011","unstructured":"Lu, A. et al. Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity. Eur. J. Drug Metab. Pharmacokinet. 36, 1\u201316 (2011).","journal-title":"Eur. J. Drug Metab. Pharmacokinet."}],"container-title":["Nature Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41557-026-02129-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41557-026-02129-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41557-026-02129-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T22:02:29Z","timestamp":1780610549000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41557-026-02129-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["2129"],"URL":"https:\/\/doi.org\/10.1038\/s41557-026-02129-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv-2024-t0t94","asserted-by":"object"}]},"ISSN":["1755-4330","1755-4349"],"issn-type":[{"value":"1755-4330","type":"print"},{"value":"1755-4349","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]},"assertion":[{"value":"26 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}