{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:59:43Z","timestamp":1780639183750,"version":"3.54.1"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic & Medicinal Chemistry"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.bmc.2025.118418","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T04:06:09Z","timestamp":1758773169000},"page":"118418","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Structure-based design, synthesis, and evaluation of tetrahydrotriazolothiazepine derivatives as novel 11\u03b2-hydroxysteroid dehydrogenase type 1 inhibitors"],"prefix":"10.1016","volume":"132","author":[{"given":"Yukinobu","family":"Numata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Shinozuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Honzumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinami","family":"Kanayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Aoyagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Ofune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanae","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Imamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chizuko","family":"Yahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Obuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Moritomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2025.118418_bb0005","first-page":"55","article-title":"How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions","volume":"21","author":"Sapolsky","year":"2000","journal-title":"Endocr Rev"},{"key":"10.1016\/j.bmc.2025.118418_bb0010","doi-asserted-by":"crossref","first-page":"5593","DOI":"10.1210\/jc.2003-030871","article-title":"Diagnosis and complications of Cushing\u2019s syndrome: a consensus statement","volume":"88","author":"Arnaldi","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.bmc.2025.118418_bb0015","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/ddr.20124","article-title":"Glucocorticoids in type 2 diabetes mellitus and the metabolic syndrome","volume":"67","author":"Welles","year":"2006","journal-title":"Drug Dev Res"},{"key":"10.1016\/j.bmc.2025.118418_rf0020","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.drudis.2007.06.001","article-title":"Inhibition of 11\u03b2-hydroxysteroid dehydrogenase type 1 as a promising therapeutic target","volume":"12","author":"Wamil","year":"2007","journal-title":"Drug Discov Today"},{"key":"10.1016\/j.bmc.2025.118418_rf0025","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1210\/er.2012-1050","article-title":"11\u03b2-hydroxysteroid dehydrogenase 1: translational and therapeutic aspects","volume":"34","author":"Gathercole","year":"2013","journal-title":"Endocr Rev"},{"key":"10.1016\/j.bmc.2025.118418_bb0025","doi-asserted-by":"crossref","first-page":"14924","DOI":"10.1073\/pnas.94.26.14924","article-title":"11\u03b2-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress","volume":"94","author":"Kotelevtsev","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.bmc.2025.118418_bb0030","doi-asserted-by":"crossref","first-page":"931","DOI":"10.2337\/diabetes.53.4.931","article-title":"Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11\u03b2-hydroxysteroid dehydrogenase type 1-deficient mice","volume":"53","author":"Morton","year":"2004","journal-title":"Diabetes"},{"key":"10.1016\/j.bmc.2025.118418_bb0035","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1126\/science.1066285","article-title":"A transgenic model of visceral obesity and the metabolic syndrome","volume":"294","author":"Masuzaki","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.bmc.2025.118418_bb0040","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2022.128782","article-title":"Discovery of 1\u2032-(1-phenylcyclopropane-carbonyl)-3H-spiro[isobenzofuran-1,3\u2032-pyrrolidin]-3-one as a novel steroid mimetic scaffold for the potent and tissue-specific inhibition of 11\u03b2-HSD1 using a scaffold-hopping approach","volume":"69","author":"Zhang","year":"2022","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmc.2025.118418_bb0045","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/joim.13741","article-title":"11\u03b2-hydroxysteroid dehydrogenase and the brain: not (yet) lost in translation","volume":"295","author":"Seckl","year":"2024","journal-title":"J Intern Med"},{"key":"10.1016\/j.bmc.2025.118418_bb0050","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/ijd.16967","article-title":"Role of corticosteroids in skin physiology and therapeutic potential of an 11\u03b2-HSD1 inhibitor: a review","volume":"63","author":"Hall","year":"2024","journal-title":"Int J Dermatol"},{"key":"10.1016\/j.bmc.2025.118418_bb0055","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s12272-025-01534-4","article-title":"A novel 11\u03b2-HSD1 inhibitor ameliorates liver fibrosis by inhibiting the notch signaling pathway and increasing NK cell population","volume":"48","author":"Kim","year":"2025","journal-title":"Arch Pharm Res"},{"key":"10.1016\/j.bmc.2025.118418_bb0060","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2019.113632","article-title":"Protective effect of a novel selective 11\u03b2-HSD1 inhibitor on eye ischemia-reperfusion induced glaucoma","volume":"169","author":"Choi","year":"2019","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.bmc.2025.118418_bb0065","doi-asserted-by":"crossref","first-page":"3628","DOI":"10.7150\/ijbs.82933","article-title":"11\u03b2-hydroxysteroid dehydrogenase type 1 facilitates osteoporosis by turning on osteoclastogenesis through hippo signaling","volume":"19","author":"Li","year":"2023","journal-title":"Int J Biol Sci"},{"key":"10.1016\/j.bmc.2025.118418_rf0075","doi-asserted-by":"crossref","first-page":"4466","DOI":"10.1021\/jm4014746","article-title":"Medicinal chemistry of inhibitors of 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1)","volume":"57","author":"Scott","year":"2014","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2025.118418_rf0080","doi-asserted-by":"crossref","first-page":"367","DOI":"10.4155\/fmc.10.282","article-title":"Crystal structures of 11\u03b2-hydroxysteroid dehydrogenase type 1 and their use in drug discovery","volume":"3","author":"Thomas","year":"2011","journal-title":"Future Med Chem"},{"key":"10.1016\/j.bmc.2025.118418_bb0075","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.2174\/156802611795860988","article-title":"Small molecule 11\u03b2-hydroxysteroid dehydrogenase type 1 inhibitors","volume":"11","author":"Sun","year":"2011","journal-title":"Curr Top Med Chem"},{"key":"10.1016\/j.bmc.2025.118418_bb0080","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.1016\/j.bmcl.2005.06.040","article-title":"Adamantyl triazoles as selective inhibitors of 11\u03b2-hydroxysteroid dehydrogenase type 1","volume":"15","author":"Olson","year":"2005","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmc.2025.118418_bb0085","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1016\/j.bmcl.2008.04.014","article-title":"Phenylcyclobutyl triazoles as selective inhibitors of 11\u03b2-hydroxysteroid dehydrogenase type I","volume":"18","author":"Zhu","year":"2008","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmc.2025.118418_bb0090","doi-asserted-by":"crossref","first-page":"4481","DOI":"10.1021\/jm100242d","article-title":"Discovery of a potent, orally active 11\u03b2-hydroxysteroid dehydrogenase type 1 inhibitor for clinical study: identification of (S)-2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221)","volume":"53","author":"V\u00e9niant","year":"2010","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2025.118418_bb0095","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1016\/j.bmcl.2009.05.011","article-title":"N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11\u03b2-hydroxysteroid dehydrogenase type 1: discovery of PF-915275","volume":"19","author":"Siu","year":"2009","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmc.2025.118418_bb0100","doi-asserted-by":"crossref","first-page":"5958","DOI":"10.1016\/j.bmcl.2006.08.129","article-title":"Adamantane 11-\u03b2-HSD-1 inhibitors: application of an isocyanide multicomponent reaction","volume":"16","author":"Sorensen","year":"2006","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmc.2025.118418_bb0105","doi-asserted-by":"crossref","first-page":"5266","DOI":"10.1016\/j.bmcl.2005.08.052","article-title":"Discovery of 4-heteroarylbicyclo[2.2.2]octyltriazoles as potent and selective inhibitors of 11\u03b2-HSD1: novel therapeutic agents for the treatment of metabolic syndrome","volume":"15","author":"Gu","year":"2005","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmc.2025.118418_bb0110","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1016\/j.bmcl.2011.01.018","article-title":"Bicyclo[2.2.2]octyltriazole inhibitors of 11\u03b2-hydoxysteroid dehydrogenase type 1. Pharmacological agents for the treatment of metabolic syndrome","volume":"21","author":"Maletic","year":"2011","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmc.2025.118418_bb0115","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.1016\/j.bmcl.2008.04.013","article-title":"4-Methyl-5-phenyl triazoles as selective inhibitors of 11\u03b2-hydroxysteroid dehydrogenase type I","volume":"18","author":"Zhu","year":"2008","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmc.2025.118418_bb0120","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1016\/j.bmcl.2011.01.125","article-title":"Substituted phenyl triazoles as selective inhibitors of 11\u03b2-hydroxysteroid dehydrogenase type 1","volume":"21","author":"Sun","year":"2011","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmc.2025.118418_bb0125","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1084\/jem.20050119","article-title":"11\u03b2-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice","volume":"202","author":"Hermanowski-Vosatka","year":"2005","journal-title":"J Exp Med"},{"key":"10.1016\/j.bmc.2025.118418_bb0130","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1021\/acsmedchemlett.8b00307","article-title":"Discovery of clinical candidate BMS-823778 as an inhibitor of human 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD-1)","volume":"9","author":"Li","year":"2018","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.bmc.2025.118418_bb0135","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1021\/ci800324m","article-title":"Identifying and characterizing binding sites and assessing druggability","volume":"49","author":"Halgren","year":"2009","journal-title":"J Chem Inf Model"},{"key":"10.1016\/j.bmc.2025.118418_bb0140","doi-asserted-by":"crossref","first-page":"7953","DOI":"10.1021\/jm801073z","article-title":"Further studies with the 2-amino-1,3-thiazol-4(5H)-one class of 11\u03b2-hydroxysteroid dehydrogenase type 1 inhibitors: reducing pregnane X receptor activity and exploring activity in a monkey pharmacodynamic model","volume":"51","author":"Fotsch","year":"2008","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2025.118418_bb0145","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1080\/00498250601050412","article-title":"Attenuating pregnane X receptor (PXR) activation: a molecular modelling approach","volume":"37","author":"Gao","year":"2007","journal-title":"Xenobiotica"},{"key":"10.1016\/j.bmc.2025.118418_bb0150","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1016\/j.bmcl.2010.03.032","article-title":"The development and SAR of pyrrolidine carboxamide 11\u03b2-HSD1 inhibitors","volume":"20","author":"Cheng","year":"2010","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmc.2025.118418_bb0155","doi-asserted-by":"crossref","first-page":"6440","DOI":"10.1021\/jacs.5b03428","article-title":"Bond-weakening catalysis: Conjugate aminations enabled by the soft homolysis of strong N\u2013H bonds","volume":"133","author":"Tarantino","year":"2015","journal-title":"J Am Chem Soc"},{"key":"10.1016\/j.bmc.2025.118418_bb0160","doi-asserted-by":"crossref","first-page":"14200","DOI":"10.1021\/ja205405n","article-title":"Intramolecular aryne-ene reaction: synthetic and mechanistic studies","volume":"133","author":"Candito","year":"2011","journal-title":"J Am Chem Soc"},{"key":"10.1016\/j.bmc.2025.118418_bb0165","doi-asserted-by":"crossref","first-page":"4608","DOI":"10.1016\/j.tet.2015.05.026","article-title":"Formal synthesis of degraded sterol (+)-aplykurodinone-1","volume":"71","author":"Singh","year":"2015","journal-title":"Tetrahedron"},{"key":"10.1016\/j.bmc.2025.118418_bb0170","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","article-title":"Processing of X-ray diffraction data collected in oscillation mode","volume":"276","author":"Otwinowski","year":"1997","journal-title":"Methods Enzymol"},{"key":"10.1016\/j.bmc.2025.118418_bb0175","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1107\/S0021889807021206","article-title":"Phaser crystallographic software","volume":"40","author":"McCoy","year":"2007","journal-title":"J Appl Cryst"},{"key":"10.1016\/j.bmc.2025.118418_bb0180","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1107\/S0907444996012255","article-title":"Refinement of macromolecular structures by the maximum-likelihood method","volume":"53","author":"Murshudov","year":"1997","journal-title":"Acta Crystallogr Sect D: Biol Crystallogr"},{"key":"10.1016\/j.bmc.2025.118418_bb0185","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1107\/S2059798319011471","article-title":"Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix","volume":"75","author":"Liebschner","year":"2019","journal-title":"Acta Crystallogr, Sect D: Struct Biol"},{"key":"10.1016\/j.bmc.2025.118418_bb0190","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr Sect D: Biol Crystallogr"}],"container-title":["Bioorganic & Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089625003591?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089625003591?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:01:32Z","timestamp":1780635692000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0968089625003591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":40,"alternative-id":["S0968089625003591"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2025.118418","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Structure-based design, synthesis, and evaluation of tetrahydrotriazolothiazepine derivatives as novel 11\u03b2-hydroxysteroid dehydrogenase type 1 inhibitors","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2025.118418","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118418"}}