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Exploring N-acyl-4-azatetracyclo[5.3.2.0 2,6 .0 8,10 ]dodec-11-enes as 11β-HSD1 Inhibitors.
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.
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