Minor structural modifications to the bicyclo-[3.1.0]-hexane core of 8 to give H and 12 were reported to have at least a 25-fold increase in ED50 values over 8. These compounds inhibited forskolin-stimulated accumulation of cAMP in mGluR2-expressing CHO cells as an indicator of their effects (27,28).

In contrast, analogs in which the keto group on the bicyclo-[3.1.0]-hexane core is replaced with a urea moiety appears to convert these types of molecules to an mGluR3 agonist. It is reported that selectivity of 13 is at least 53-fold for mGluR3 versus mGluR2 receptors, Ki = 9.54 nM vs Ki = 511.5 nM, respectively (29).

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