Table 6. mGlu5 Potency and Protein Binding in the Thiazolotriazole Series.
entry | R1 | R2 | R3 | R4 | mGlu5 IC50 (nM) | fub | pIC50 eff |
---|---|---|---|---|---|---|---|
82 | H | H | H | phenyl | >30 000 | ||
83 | H | Me | H | phenyl | >30 000 | ||
84 | H | H | Me | phenyl | 10 000 | ||
85 | H | Me | Me | phenyl | 63 | 6.8 | 6.0 |
86 | H | Me | Me | cyclohexyl | 3200 | ||
87 | H | Me | Me | 3-chlorophenyl | 40 | 0.9 | 5.4 |
88 | H | Me | Me | 3-fluorophenyl | 50 | 1.7 | 5.5 |
89 | H | Me | Me | 3-pyridyl | 316 | 28 | 5.9 |
90 | cyclopropyl | Me | Me | phenyl | 13 | ||
91 | thiophen-2-yl | Me | Me | phenyl | 7.9 | <0.1 | <5.0 |