{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T12:13:16Z","timestamp":1783512796971,"version":"3.55.0"},"reference-count":46,"publisher":"Royal Society of Chemistry (RSC)","issue":"26","license":[{"start":{"date-parts":[[2027,6,12]],"date-time":"2027-06-12T00:00:00Z","timestamp":1812758400000},"content-version":"am","delay-in-days":527,"URL":"http:\/\/rsc.li\/journals-terms-of-use"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 113-2113-M-002-018-MY2"],"award-info":[{"award-number":["NSTC 113-2113-M-002-018-MY2"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 113-2628-M-002-014-MY4"],"award-info":[{"award-number":["NSTC 113-2628-M-002-014-MY4"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 114-2113-M-003-016"],"award-info":[{"award-number":["NSTC 114-2113-M-003-016"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006477","name":"National Taiwan University","doi-asserted-by":"publisher","award":["NTU-CDP-113L7769"],"award-info":[{"award-number":["NTU-CDP-113L7769"]}],"id":[{"id":"10.13039\/501100006477","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019393","name":"Center for Emerging Material and Advanced Devices, National Taiwan University","doi-asserted-by":"publisher","award":["NTU-CC-113L894202"],"award-info":[{"award-number":["NTU-CC-113L894202"]}],"id":[{"id":"10.13039\/501100019393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019393","name":"Center for Emerging Material and Advanced Devices, National Taiwan University","doi-asserted-by":"publisher","award":["NTU-CC-113L895203"],"award-info":[{"award-number":["NTU-CC-113L895203"]}],"id":[{"id":"10.13039\/501100019393","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":["Org. Biomol. Chem."],"abstract":"<jats:p>Substituted bicyclo[2.2.2]oct-2-enes serve as accessible non-classical benzene isosteres, supported by structural and biological studies.<\/jats:p>","DOI":"10.1039\/d6ob00798h","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:43:26Z","timestamp":1781225006000},"page":"5488-5493","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, synthesis, and evaluation of trisubstituted bicyclo[2.2.2]oct-2-enes as non-classical isosteres of trisubstituted benzenes"],"prefix":"10.1039","volume":"24","author":[{"given":"Chih-Wei","family":"Hsu","sequence":"first","affiliation":[{"name":"Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Jie","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jin","family":"Jheng","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hui","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Taiwan Normal University, No. 162, Sec. 1, Heping E. Road, Taipei 11677, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Meng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Taiwan Normal University, No. 162, Sec. 1, Heping E. Road, Taipei 11677, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2842-3377","authenticated-orcid":false,"given":"Sung-Fang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Taiwan Normal University, No. 162, Sec. 1, Heping E. Road, Taipei 11677, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7033-7229","authenticated-orcid":false,"given":"John","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan"},{"name":"Center for Emerging Materials and Advanced Devices, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1207-9399","authenticated-orcid":false,"given":"Woo-Jin","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan"},{"name":"Center for Emerging Materials and Advanced Devices, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"292","published-online":{"date-parts":[[2026]]},"reference":[{"key":"D6OB00798H\/cit1a\/1","doi-asserted-by":"crossref","first-page":"5845","DOI":"10.1021\/jm4017625","volume":"57","author":"Taylor","year":"2014","journal-title":"J. Med. Chem."},{"key":"D6OB00798H\/cit1b\/1","doi-asserted-by":"crossref","first-page":"8699","DOI":"10.1021\/acs.jmedchem.2c00473","volume":"65","author":"Shearer","year":"2022","journal-title":"J. Med. Chem."},{"key":"D6OB00798H\/cit1c\/1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/B978-012373944-5.00331-X","volume-title":"Encyclopedia of Microbiology","author":"Espinel-Ingroff","year":"2009","unstructured":"A.Espinel-Ingroff , in  Encyclopedia of Microbiology , ed.  M. Schaechter ,  Academic Press ,  San Diego, CA , 3rd edn,  2009 , pp.  205\u2013222"},{"key":"D6OB00798H\/cit2a\/1","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.drudis.2009.07.014","volume":"14","author":"Ritchie","year":"2009","journal-title":"Drug Discovery Today"},{"key":"D6OB00798H\/cit2b\/1","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.drudis.2010.11.014","volume":"16","author":"Ritchie","year":"2011","journal-title":"Drug Discovery Today"},{"key":"D6OB00798H\/cit3\/1","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.1021\/jm901241e","volume":"52","author":"Lovering","year":"2009","journal-title":"J. Med. Chem."},{"key":"D6OB00798H\/cit4a\/1","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1039\/C8OB02812E","volume":"17","author":"Mykhailiuk","year":"2019","journal-title":"Org. Biomol. Chem."},{"key":"D6OB00798H\/cit4b\/1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.3762\/bjoc.20.78","volume":"20","author":"Diepers","year":"2024","journal-title":"Beilstein J. Org. Chem."},{"key":"D6OB00798H\/cit4c\/1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/s41570-024-00623-0","volume":"8","author":"Tsien","year":"2024","journal-title":"Nat. Rev. Chem."},{"key":"D6OB00798H\/cit4d\/1","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1055\/a-2360-8218","author":"Nagasawa","year":"2025","journal-title":"Synthesis"},{"key":"D6OB00798H\/cit5a\/1","doi-asserted-by":"crossref","first-page":"27030","DOI":"10.1021\/jacs.5c09523","volume":"147","author":"Zhou","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"D6OB00798H\/cit5b\/1","doi-asserted-by":"crossref","first-page":"50468","DOI":"10.1021\/acsomega.5c07982","volume":"10","author":"D\u00e1vila","year":"2025","journal-title":"ACS Omega"},{"key":"D6OB00798H\/cit6a\/1","doi-asserted-by":"crossref","first-page":"20515","DOI":"10.1002\/anie.202004183","volume":"59","author":"Denisenko","year":"2020","journal-title":"Angew. Chem., Int. Ed."},{"key":"D6OB00798H\/cit6b\/1","doi-asserted-by":"crossref","first-page":"e2108881118","DOI":"10.1073\/pnas.2108881118","volume":"118","author":"Zhao","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"D6OB00798H\/cit6c\/1","doi-asserted-by":"crossref","first-page":"14092","DOI":"10.1039\/D3SC05121H","volume":"14","author":"Denisenko","year":"2023","journal-title":"Chem. Sci."},{"key":"D6OB00798H\/cit6d\/1","doi-asserted-by":"crossref","first-page":"e202303548","DOI":"10.1002\/chem.202303548","volume":"30","author":"Fujiwara","year":"2024","journal-title":"Chem. \u2013 Eur. J."},{"key":"D6OB00798H\/cit7\/1","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1039\/C7MD00381A","volume":"8","author":"de Freitas","year":"2017","journal-title":"Med. Chem. Commun."},{"key":"D6OB00798H\/cit8\/1","doi-asserted-by":"crossref","first-page":"34427","DOI":"10.1021\/jacs.4c10968","volume":"146","author":"Li","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"D6OB00798H\/cit9a\/1","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1021\/cr00095a003","volume":"89","author":"Griffin","year":"1989","journal-title":"Chem. Rev."},{"key":"D6OB00798H\/cit9b\/1","doi-asserted-by":"crossref","first-page":"6719","DOI":"10.1021\/cr500523x","volume":"115","author":"Biegasiewicz","year":"2015","journal-title":"Chem. Rev."},{"key":"D6OB00798H\/cit10a\/1","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/s41586-023-06021-8","volume":"618","author":"Wiesenfeldt","year":"2023","journal-title":"Nature"},{"key":"D6OB00798H\/cit10b\/1","doi-asserted-by":"crossref","first-page":"7971","DOI":"10.1039\/D3CC02164E","volume":"59","author":"Kazi","year":"2023","journal-title":"Chem. Commun."},{"key":"D6OB00798H\/cit11a\/1","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.1021\/ja00714a075","volume":"92","author":"Cassar","year":"1970","journal-title":"J. Am. Chem. Soc."},{"key":"D6OB00798H\/cit11b\/1","doi-asserted-by":"crossref","first-page":"6366","DOI":"10.1021\/ja00724a061","volume":"92","author":"Eaton","year":"1970","journal-title":"J. Am. Chem. Soc."},{"key":"D6OB00798H\/cit12a\/1","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1002\/hlca.19790620830","volume":"62","author":"Grob","year":"1979","journal-title":"Helv. Chim. Acta"},{"key":"D6OB00798H\/cit12b\/1","doi-asserted-by":"crossref","first-page":"14010","DOI":"10.1002\/chem.201901208","volume":"25","author":"Ling","year":"2019","journal-title":"Chem. \u2013 Eur. J."},{"key":"D6OB00798H\/cit13\/1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.pestbp.2012.07.010","volume":"104","author":"Berdugo","year":"2012","journal-title":"Pestic. Biochem. Physiol."},{"key":"D6OB00798H\/cit15\/1","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1021\/acs.orglett.9b00765","volume":"21","author":"Zhang","year":"2019","journal-title":"Org. Lett."},{"key":"D6OB00798H\/cit16\/1","doi-asserted-by":"crossref","first-page":"8503","DOI":"10.1021\/acs.orglett.2c03396","volume":"24","author":"Vidal","year":"2022","journal-title":"Org. Lett."},{"key":"D6OB00798H\/cit17\/1","doi-asserted-by":"crossref","first-page":"5096","DOI":"10.1021\/acscatal.3c00305","volume":"13","author":"Liu","year":"2023","journal-title":"ACS Catal."},{"key":"D6OB00798H\/cit18\/1","doi-asserted-by":"crossref","first-page":"2195001","DOI":"10.1080\/01443615.2023.2195001","volume":"43","author":"Regidor","year":"2023","journal-title":"J. Obstet. Gynaecol."},{"key":"D6OB00798H\/cit19\/1","doi-asserted-by":"crossref","first-page":"14069","DOI":"10.1002\/chem.201001814","volume":"16","author":"Axenov","year":"2010","journal-title":"Chem. \u2013 Eur. J."},{"key":"D6OB00798H\/cit20\/1","doi-asserted-by":"crossref","first-page":"14901","DOI":"10.1002\/anie.201906815","volume":"58","author":"Hofstra","year":"2019","journal-title":"Angew. Chem., Int. Ed."},{"key":"D6OB00798H\/cit21\/1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1021\/ml1000307","volume":"1","author":"Pan","year":"2010","journal-title":"ACS Med. Chem. Lett."},{"key":"D6OB00798H\/cit22\/1","doi-asserted-by":"crossref","first-page":"8015","DOI":"10.1016\/j.tet.2016.10.038","volume":"72","author":"Shklyaruck","year":"2016","journal-title":"Tetrahedron"},{"key":"D6OB00798H\/cit23\/1","doi-asserted-by":"crossref","first-page":"5541","DOI":"10.1021\/acs.orglett.2c02023","volume":"24","author":"Ma","year":"2022","journal-title":"Org. Lett."},{"key":"D6OB00798H\/cit24\/1","doi-asserted-by":"crossref","first-page":"e693","DOI":"10.1002\/iid3.693","volume":"10","author":"Cai","year":"2022","journal-title":"Immun., Inflammation Dis."},{"key":"D6OB00798H\/cit25\/1","first-page":"e70019","volume":"15","author":"Neese","year":"2025","journal-title":"Wiley Interdiscip. Rev.: Comput. Mol. Sci."},{"key":"D6OB00798H\/cit26a\/1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1103\/PhysRevB.37.785","volume":"37","author":"Lee","year":"1988","journal-title":"Phys. Rev. B:Condens. Matter Mater. Phys."},{"key":"D6OB00798H\/cit26b\/1","doi-asserted-by":"crossref","first-page":"5648","DOI":"10.1063\/1.464913","volume":"98","author":"Becke","year":"1993","journal-title":"J. Chem. Phys."},{"key":"D6OB00798H\/cit26c\/1","doi-asserted-by":"crossref","first-page":"154122","DOI":"10.1063\/1.5090222","volume":"150","author":"Caldeweyher","year":"2019","journal-title":"J. Chem. Phys."},{"key":"D6OB00798H\/cit26d\/1","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1039\/b508541a","volume":"7","author":"Weigend","year":"2005","journal-title":"Phys. Chem. Chem. Phys."},{"key":"D6OB00798H\/cit29\/1","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1021\/jm101356p","volume":"54","author":"Ishikawa","year":"2011","journal-title":"J. Med. Chem."},{"key":"D6OB00798H\/cit30\/1","unstructured":"The replacement of the benzene ring with bicyclo[2.2.2]octane results in lower solubility. See"},{"key":"D6OB00798H\/cit30\/2","doi-asserted-by":"crossref","first-page":"5608","DOI":"10.1038\/s41467-023-41298-3","volume":"14","author":"Levterov","year":"2023","journal-title":"Nat. Commun."},{"key":"D6OB00798H\/cit31\/1","unstructured":"Representative images of colonies formed by HeLa cells in a colony formation assay can be found in the SI"}],"container-title":["Organic &amp; Biomolecular Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/pubs.rsc.org\/en\/content\/articlepdf\/2026\/OB\/D6OB00798H","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T11:14:24Z","timestamp":1783509264000},"score":1,"resource":{"primary":{"URL":"https:\/\/xlink.rsc.org\/?DOI=D6OB00798H"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":46,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2026,7,8]]}},"URL":"https:\/\/doi.org\/10.1039\/d6ob00798h","relation":{},"ISSN":["1477-0520","1477-0539"],"issn-type":[{"value":"1477-0520","type":"print"},{"value":"1477-0539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]}}}