TABLE 1

Empirical potency (EC50) versus operational model parameters describing the functional affinity (KB), global cooperativity (αβ), and direct agonism (τB) of thienopyridine allosteric ligands for modulating acetylcholine-mediated ERK1/2 phosphorylation at the M4 mAChR

Adapted from Huynh et al. (2013).

Embedded Image
CompoundRpEC50 (EC50, μM)pKB (KB, μM)Logαβ (αβ)LogτB (τB)
1a4-OCH36.89 (0.13)5.95 (1.14)0.68 (4.77)0.22 (1.68)
1b3-OCH36.25 (0.56)4.95 (11.4)1.37 (23.4)0.34 (2.18)
1c2-OCH3NANANANA
1d3,4-(OCH3)2NANANANA
1e3,5-(OCH3)2NANANANA
1f3,4,5-(OCH3)3NANANANA
1g2-F6.90 (0.13)5.93 (1.17)1.10 (12.4)0.36 (2.30)
1h3-F6.51 (0.31)5.21 (6.24)1.63 (42.2)0.76 (5.71)
1i4-F6.66 (0.22)5.60 (2.52)1.12 (13.2)0.44 (2.77)
1j2,3-F26.98 (0.11)5.76 (1.72)1.15 (14.3)0.45 (2.80)
1k2,5-F26.88 (0.13)5.77 (1.69)0.76 (5.70)0.15 (1.43)
1l2,4,5-F36.24 (0.58)5.63 (2.32)0.70 (4.96)−0.27 (0.54)
1m2,3,5-F36.85 (0.14)5.89 (1.29)0.81 (6.41)0.03 (1.08)
1n3-F-4-OCH37.00 (0.10)5.59 (2.58)1.53 (34.0)0.48 (3.04)
1o2-F-4-OCH36.46 (0.35)5.74 (1.82)0.49 (3.11)−1.12 (0.08)
1p2,3-F2-4-OCH36.62 (0.24)5.73 (1.88)0.83 (6.69)0.41 (2.59)
1q2,5-F2-4-OCH3NANANANA
  • NA, not applicable.