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http://hdl.handle.net/2445/128385
Title: | Novel 11β-HSD1 inhibitors: C-1 versus C-2 substitution and effect of the introduction of an oxygen atom in the adamantane scaffold |
Author: | Leiva Martínez, Rosana Seira Castán, Constantí McBride, Andrew Binnie, Margaret Luque Garriga, F. Xavier Bidon-Chanal Badia, Axel Webster, Scott P. Vázquez Cruz, Santiago |
Keywords: | Biologia Farmacologia Medicaments antivírics Síntesi orgànica Investigació farmacèutica Cromatografia Isomerització Reaccions químiques Biology Pharmacology Antiviral agents Organic synthesis Pharmaceutical research Chromatography Isomerization Chemical reactions |
Issue Date: | 5-Aug-2015 |
Publisher: | Elsevier Ltd |
Abstract: | 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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1016/j.bmcl.2015.07.097 |
It is part of: | Bioorganic & Medicinal Chemistry Letters, 2015, vol. 25, num. 19, p. 4250-4253 |
URI: | http://hdl.handle.net/2445/128385 |
Related resource: | https://doi.org/10.1016/j.bmcl.2015.07.097 |
ISSN: | 0960-894X |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia) |
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