Table 1.
Structures and mAChR activities of analogs 5, 14a–o.
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Compound | R | hM4 IC50 (μM)a [% ACh Min ±SEM] | hM4 pIC50 (±SEM)a |
5 | 4-Et | 0.38 [5.3±0.7] | 6.46±0.09 |
14a | H | 0.65 [2.7±0.3] | 6.21±0.09 |
14b | 4-Me | 0.31 [3.3±0.2] | 6.52±0.08 |
14c | 2-naphthyl | 0.71 [6.8±2.2] | 6.16±0.06 |
14d | 3,4-methylenedioxy | 0.51 [4.1±0.3] | 6.30±0.09 |
14e | 4-F | 0.24 [3.5±0.2] | 6.64±0.02 |
14f | 3-F | 0.31 [3.2±0.3] | 6.52±0.06 |
14g | 2-F | 0.13 [3.2±0.5] | 6.91±0.08 |
14h | 4-Cl | 0.14 [3.0±0.2] | 6.88±0.07 |
14i | 4-OMe | 0.46 [5.3±1.0] | 6.30±0.06 |
14j | 2,3-diF | 0.19 [3.1±0.1] | 6.77±0.15 |
14k | 2,4-diF | 0.10 | 7.00±0.08 |
14l | 2,5-diF | 0.08 [3.1±0.2] | 7.11±0.11 |
14m | 2,6-diF | 2.72 [7.0±0.9] | 5.57±0.05 |
14n | 2-F, 4-Cl | 0.15 [3.1±0.3] | 6.93±0.06 |
14o | 2,4-diCl | 0.27 [3.0±0.1] | 6.58±0.09 |
Mean of three independent determinations in a calcium mobilization assay using recombinant hM4-expressing Chinese hamster ovary cells co-transfected with chimeric Gqi5 in the presence of an ACh EC80.