Table 1.

SAR of 6,6 fused ring heterocycles

Compound	Structurea	mGlu5 IC50 (nM)b	% Glu Maxc	Synthetic Conditions
3		9.5 ± 1.6	1.2 ± 0.3	i
5		182 ± 114	1.8 ± 0.2	ii
6		133 ± 63	2.6 ± 0.6	iii
7		>30,000	–	ii
8		1190 ± 61	20.1 ± 4.1	i
9		6000 ± 663	12.4 ± 1.6	i
10		>30,000	–	i
11		>10,000d	54.0 ± 6.4	i
12		>30,000	–	ii
13		>10,000d	66.6	ii

^aR = 3-cyano-5-fluorophenyl

^bCalcium mobilization mGlu5 assay; values are average of n ≥ 3

^cAmplitude of response in the presence of 30 μM test compound as a percentage of maximal response (100 μM glutamate); values are average of n ≥ 3

^dCRC does not plateau