Table 2.

SAR of 5,6 fused ring heterocycles

Compound	Structurea	mGlu5 IC50 (nM)b	% Glu Maxc	Synthetic Conditions
14		>30,000	–	i
15		2460 ± 226	26.3 ± 14.4	iii
16		>10,000d	46.5 ± 7.8	i
17		>30,000	–	i
18		61 ± 7	0.63 ± 0.12	i
19		>30,000	–	iii
20		>30,000	–	iii
21		>10,000d	60.4 ± 2.5	iii
22		>30,000	–	from 21e
23		1520 ± 296	4.8 ± 2.3	from 21e

^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

^eReaction of 21 with K₂CO₃ and MeI in DMF afforded a separable mixture of 22 and 23