Exploring N-acyl-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-enes as 11β-HSD1 Inhibitors
Rosana Leiva,
Andrew McBride,
Margaret Binnie,
Scott P. Webster,
Santiago Vázquez
Affiliations
Rosana Leiva
Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de l’Alimentació, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Joan XXIII, 27-31, E-08028 Barcelona, Spain
Andrew McBride
Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh EH16 4TJ, UK
Margaret Binnie
Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh EH16 4TJ, UK
Scott P. Webster
Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh EH16 4TJ, UK
Santiago Vázquez
Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de l’Alimentació, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Joan XXIII, 27-31, E-08028 Barcelona, Spain
We recently found that a cyclohexanecarboxamide derived from 4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-ene displayed low nanomolar inhibition of 11β-HSD1. In continuation of our efforts to discover potent and selective 11β-HSD1 inhibitors, herein we explored several replacements for the cyclohexane ring. Some derivatives exhibited potent inhibitory activity against human 11β-HSD1, although with low selectivity over the isoenzyme 11β-HSD2, and poor microsomal stability.
