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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 2.

mGlu3 NAM and mGlu5 SAR of Western 2-Pyridyl Ethers 41–51

graphic file with name nihms-766653-f0008.jpg
no. 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
41 3-F 5.96 ± 0.02 1100 2.22 ± 0.84 PAM 5.37 ± 0.06 4300 78.5 ± 6.1
42 3-CF3 5.53 ± 0.02 2940 2.11 ± 0.96 <4.5 >30000
43 3-OMe 5.17 ± 0.02 6760 –1.14 ± 2.54 <4.5 >30000
44 4-Me 5.68 ± 0.01 2090 0.86 ± 0.47 NAMd <5.0 >10000 46.9 ± 5.9
45 4-CF3 5.78 ± 0.01 1670 1.62 ± 0.42 NAMd <5.0 >10000 12.9 ± 2.9
46 4-OMe 5.43 ± 0.00 3690 –0.18 ± 1.39 NAMd <5.0 >10000 54.7 ± 5.8
47 5-F 6.27 ± 0.02 539 1.71 ± 0.55 NAMd <5.0 >10000 46.5 ± 3.4
48 5-Cl 6.22 ± 0.04 605 1.84 ± 0.51 PAM 5.53 ± 0.06 2920 81.4 ± 2.7
49 6-Me 5.62 ± 0.02 2370 1.12 ± 1.08 NAM 5.65 ± 0.07 2250 2.47 ± 0.17
50 6-CF3 5.63 ± 0.02 2360 2.06 ± 0.79 <4.5 >30000
51 6-OMe 5.80 ± 0.02 1590 1.94 ± 0.62 PAMd <5.0 >10000 31.2 ± 3.1
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.

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