Table 2. Metabolic Stability, cLogBB, and CNS MPO Values for Relevant C8 Analoguesa.
| compound | stability (2 h, microsomes) (%) | stability (2 h, no microsomes) (%) | cLogBB | CNS MPO |
|---|---|---|---|---|
| propranolol | 68 ± 2 | 102 ± 3 | ND | ND |
| TMZ | 87 ± 6 | 86 ± 4 | –1.58 | 4.9 |
| 4 (Me-TMZ) | 86 ± 1 | 93 ± 1 | –1.34 | 5.7 |
| 5 (DiMe-TMZ) | 81 ± 2 | 92 ± 3 | –1.18 | 6.0 |
| 6 | 81 ± 1 | 95 ± 2 | –1.07 | 6.0 |
| 7 | 1 ± 1 | 98 ± 3 | –0.78 | 5.6 |
| 17 (K-TMZ) | 70 ± 1 | 77 ± 3 | –1.08 | 6.0 |
| 19 | 91 ± 3 | 91 ± 1 | –0.72 | 6.0 |
| 23 | 44 ± 2 | 103 ± 5 | –0.56 | 5.7 |
| 27 (Ox-TMZ) | 71 ± 1 | 95 ± 4 | –1.19 | 5.9 |
a
The metabolic stability was assessed in mouse liver microsomes. Compounds were incubated with microsomes for 2 h before the percentage remaining was quantified relative to t0. Experiments assessing stability in the absence of microsomes were identical but replaced liver microsomes with PBS. Error is SEM, n ≥ 2. Internal standard = N3-propyl TMZ. CNS MPO = central nervous system multiparameter optimization score.