Table 3. Reverse Amide SAR.

entry	R	rat mGlu1 pIC50 (±SEM)a	rat mGlu1 IC50 (nM)	rat % Glu Max (±SEM)ab	human mGlu1 pIC50 (±SEM)a	human mGlu1 IC50 (nM)	human % Glu Max (±SEM)ab
23	N-phenyl	5.92 ± 0.10	1190	4.8 ± 1.7	<4.5	>30 000
24	N-methyl-N-phenyl	<4.5	>30 000		<4.5	>30 000
25	N-2-fluorophenyl	6.64 ± 0.10	230	2.5 ± 0.7	<4.5	>30 000
26	N-2-chlorophenyl	5.93 ± 0.18	1180	2.2 ± 0.6	<4.5	>30 000
27	N-2-methylphenyl	<5.0c	>10 000	21.1 ± 7.7	<4.5	>30 000
28	N-3-fluorophenyl	6.11 ± 0.17	768	9.5 ± 3.3	<4.5	>30 000
29	N-3-chlorophenyl	6.35 ± 0.03	443	58.9 ± 12.3	<4.5	>30 000
30	N-3-methylphenyl	5.74 ± 0.25	1830	1.1 ± 0.8	<5.0c	>10 000	69.9 ± 2.7
31	N-4-fluorophenyl	5.96 ± 0.01	1100	31.8 ± 3.1	<4.5	>30 000
32	N-isopropyl	<5.0c	>10 000	19.3 ± 8.2	<4.5	>30 000
33	N-cyclohexyl	5.80 ± 0.02	1570	5.4 ± 0.4	<4.5	>30 000
34	N-(trans)-4-methylcyclohexyl	<4.5	>30 000		<4.5	>30 000
35	N-cycloheptyl	<5.0c	>10 000	20.7 ± 5.6	<4.5	>30 000
36	(R)-N-1-cyclohexylethyl	<5.0c	>10 000	62.0 ± 5.2	<4.5	>30 000
37	(S)-N-1-cyclohexylethyl	<5.0c	>10 000	16.9 ± 7.8	<4.5	>30 000
38	N-3,3-dimethylbutyl	6.13 ± 0.05	735	3.1 ± 0.4	<5.0c	>10 000	70.0 ± 3.1

^aValues are average of n ≥ 3.

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

^cCRC does not plateau.