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. Author manuscript; available in PMC: 2016 Sep 24.
Published in final edited form as: J Med Chem. 2015 Sep 10;58(18):7485–7500. doi: 10.1021/acs.jmedchem.5b01005

Table 7.

mGlu3 NAM and mGlu5 SAR of Additional 5-Chloropyridin-2-yl Ether Analogues 102–110

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no. series R mGlu3 pIC50 (± SEM)a mGlu3 IC50 (nM)a % Glu Max (± SEM)a,b mGlu5 activityc mGlu5 pEC50 (± SEM)c mGlu5 EC50 (nM)c % Glu Max (± SEM)b,c
102 I 3-F 6.44 ± 0.03 362 1.64 ± 0.36 PAMd <5.0 >10000 32.4 ± 4.4
103 I 3-CN 6.17 ± 0.06 677 1.35 ± 0.55 <4.5 >30000
104 I 5-F 6.59 ± 0.09 260 2.44 ± 0.32 PAMd <5.0 >10000 47.9 ± 5.1
105 I 6-F 6.53 ± 0.08 294 1.75 ± 0.19 NAMd <5.0 >10000 24.8 ± 5.5
106 II 2-F 6.41 ± 0.05 392 1.71 ± 0.41 <4.5 >30000
107 II 4-F 6.32 ± 0.03 482 1.45 ± 0.22 <4.5 >30000
108 II 5-F 6.32 ± 0.03 481 1.85 ± 0.32 <4.5 >30000
109 II 5-CN 6.22 ± 0.01 605 1.08 ± 0.50 <4.5 >30000
110 II 6-F 6.39 ± 0.06 408 1.45 ± 0.29 PAMd <5.0 >10000 30.6 ± 2.4
a

Calcium mobilization mGlu3 assay; values are average of n ≥ 3.

b

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

c

Calcium mobilization mGlu5 assay; values are average of n ≥ 3.

d

Weak activity; CRC does not plateau.