Table 12. mGlu5 Potency, Solubility, and Intrinsic Clearance in the Nicotinamide Series.
entry | R1 | R2 | mGlu5 IC50 (nM) | solubility at pH 6.8 (mg/mL) | rat ClINT (μL/min/mg) | human ClINT (μL/min/mg) |
---|---|---|---|---|---|---|
181 | H | H | 87 | 150 | 48 | 33 |
(R)-182 | H | R-ethyl | 40 | 95 | 643 | 322 |
(S)-182 | H | S-ethyl | 40 | <3 | 687 | 174 |
(R)-183 | R-ethyl | H | 32 | 58 | 87 | 89 |
(S)-183 | S-ethyl | H | 390 | 56 | 190 | 216 |