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cc-by-nc-nd (c) Elsevier Ltd, 2015
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/128385

Novel 11β-HSD1 inhibitors: C-1 versus C-2 substitution and effect of the introduction of an oxygen atom in the adamantane scaffold

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The adamantane scaffold is found in several marketed drugs and in many investigational 11b-HSD1 inhibitors. Interestingly, all the clinically approved adamantane derivatives are C-1 substituted. We demonstrate that, in a series of paired adamantane isomers, substitution of the adamantane in C-2 is preferred over the substitution at C-1 and is necessary for potency at human 11b-HSD1. Furthermore, the introduction of an oxygen atom in the hydrocarbon scaffold of adamantane is deleterious to 11b-HSD1 inhibition. Molecular modeling studies provide a basis to rationalize these features.

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LEIVA MARTÍNEZ, Rosana, SEIRA CASTÁN, Constantí, MCBRIDE, Andrew, BINNIE, Margaret, LUQUE GARRIGA, F. xavier, BIDON-CHANAL BADIA, Axel, WEBSTER, Scott p., VÁZQUEZ CRUZ, Santiago. Novel 11β-HSD1 inhibitors: C-1 versus C-2 substitution and effect of the introduction of an oxygen atom in the adamantane scaffold. _Bioorganic & Medicinal Chemistry Letters_. 2015. Vol. 25, núm. 19, pàgs. 4250-4253. [consulta: 27 de gener de 2026]. ISSN: 0960-894X. [Disponible a: https://hdl.handle.net/2445/128385]

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