Exploring N-acyl-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-enes as 11β-HSD1 Inhibitors

Molecules

Margaret Binnie¹  Scott P. Webster¹  Andrew McBride¹  Santiago Vázquez²  Rosana Leiva² 

[1] Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh EH16 4TJ, UK;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;

关键词: drug discovery;    enzyme inhibitors;    polycyclic hydrocarbons;    SAR investigation;    11β-HSD1;   

DOI  :  10.3390/molecules23030536

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown