Table 5.
Mouse liver microsomal (MLM) stability of selected novel EP2 antagonistsa
| Compd. | MLM T1/2 (minutes) |
|---|---|
| 3a | <2 |
| 8c | 2.9 |
| 8d | 13 |
| 8g | 2.9 |
| 14a | 6.5 |
| 20b | 8 |
| 20c | 17 |
| 20e | 12 |
| 20f | 96 |
| 20h | 16 |
| 20o | 17 |
| 24a | 17 |
| 24c | 26 |
| 24e | 15 |
| 24i | 56 |
The compounds at 1μM were incubated in 0.125 mg/mL liver microsomes that are activated with addition of NADPH (final concentration 1 mM) and quenched the reaction at 0, 5, 15, 30, 60 and 120 min using ice-cold acetonitrile. The % compound remaining was measured using LC-MS/MS from which half-life was calculated. The work was done at CRO laboratories.