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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 1.

mGlu3 NAM and mGlu5 SAR of Western Phenyl Ethers 18, 22–39

graphic file with name nihms-766653-f0007.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
18 H 6.57 ± 0.15 267 2.21 ± 0.80 PAM 7.34 ± 0.02 46 87.7 ± 1.4
22 2-F 6.28 ± 0.20 530 2.90 ± 1.05 PAM 6.71 ± 0.04 195 89.3 ± 3.0
23 3-F 6.11 ± 0.03 773 1.19 ± 0.75 PAM 7.14 ± 0.02 73 86.1 ± 2.9
24 4-F 6.34 ± 0.04 462 2.09 ± 0.57 PAM 7.03 ± 0.05 92 87.0 ± 1.0
25 2,4-di-F 6.38 ± 0.22 417 1.70 ± 0.35 PAM 6.51 ± 0.05 307 82.3 ± 2.7
26 2-Me 6.14 ± 0.14 721 1.56 ± 0.37 PAM 5.83 ± 0.04 1500 83.7 ± 2.5
27 3-Me 5.84 ± 0.05 1440 2.35 ± 0.18 NAMd <5.0 >10000 39.7 ± 7.7
28 4-Me 5.92 ± 0.02 1190 1.72 ± 0.55 PAM 5.97 ± 0.04 1080 92.5 ± 2.6
29 2-Cl 6.27 ± 0.18 532 1.63 ± 0.33 PAM 6.38 ± 0.01 419 84.4 ± 2.1
30 3-Cl 5.79 ± 0.02 1620 1.96 ± 0.11 NAMd <5.0 >10000 32.8 ± 6.1
31 4-Cl 5.93 ± 0.01 1170 1.86 ± 0.52 PAM 6.22 ± 0.04 604 81.8 ± 0.3
32 2-OMe 5.59 ± 0.18 2540 2.32 ± 1.39 PAMd <5.0 >10000 63.7 ± 3.1
33 3-OMe 5.89 ± 0.02 1290 1.78 ± 0.53 PAM 5.74 ± 0.04 1840 32.4 ± 3.0
34 4-OMe 5.98 ± 0.02 1040 1.76 ± 0.39 PAM 5.87 ± 0.16 1340 40.2 ± 4.8
35 4-CF3 5.73 ± 0.01 1850 4.13 ± 0.09 <4.5 >30000
36 4-Et 6.08 ± 0.05 830 2.29 ± 0.84 PAM 5.49 ± 0.03 3210 50.8 ± 3.7
37 4-CN 6.11 ± 0.12 784 2.53 ± 0.70 PAM 5.71 ± 0.06 1940 38.6 ± 4.8
38 4-OEt 5.94 ± 0.06 1160 3.39 ± 0.87 <4.5 >30000
39 4-OCF3 5.39 ± 0.04 4070 2.66 ± 0.34 <4.5 >30000
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; concentration response curve (CRC) does not plateau.

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