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. Author manuscript; available in PMC: 2012 Mar 14.
Published in final edited form as: ACS Comb Sci. 2011 Feb 21;13(2):159–165. doi: 10.1021/co1000508

Table 2.

SAR Evaluation of Amide Aromatic Ring

graphic file with name nihms275479t6.jpg
Cmpd n R hEC50 (µM)a % PHCCCa Yieldc (%)
9 1 2,4-dimethoxyphenyl >10 69.5 ± 7.7 61
20a 1 2-methoxyphenyl >10 63.9 ± 3.6 64
20b 1 4-methoxyphenyl Inactiveb 14.8 ± 0.8 20d
20c 1 2,4-difluorophenyl Inactiveb 17.7 ± 1.6 3d
20d 1 2-fluorophenyl Inactiveb 13.2 ± 0.4 2d
20e 1 4-pyridyl Inactiveb 13.9 ± 1.2 2d
20f 1 Cyclohexyl Inactiveb 15.5 ± 1.3 12d
20g 1 Isopropyl Inactiveb 15.0 ± 0.8 19d
20h 1 2,3-dihydrobenzo[b][1,4]dioxin-6-yl Inactiveb 17.6 ± 1.0 12d
20i 0 2,4-dimethoxyphenyl Inactiveb 13.5 ± 0.7 80
20j 3 2,4-dimethoxyphenyl
(±)-PHCCC		 Inactiveb
3.1 ± 0.3		 14.8 ± 1.3 70
a

EC50 and GluMax, are the average of at least three independent determinations performed in triplicate (Mean ± SEM shown in table). PHCCC is run as a control compound each day, and the maximal response generated in mGlu4 CHO cells in the presence of mGlu4 PAMs varies slightly in each experiment. Therefore, efficacy data were further normalized to the relative PHCCC response obtained in each day’s run.

b

Inactive compounds are defined as %GluMax did not surpass 2X the EC20 value for that day’s run.

c

All yields were obtained by reverse phase preparative HPLC unless otherwise stated and were optimized for purity (>95%) not yield.

d

Yields obtained by mass directed HPLC17