Table 2. In Vitro ADME Parameters for Novel M4K Series Compounds.
| Compound | Microsomal Stability Assayb |
Caco-2 Permeability
Assayc,d |
c Log D @ pH 7 | |||
|---|---|---|---|---|---|---|
| MLM (%) | HLM (%) | Papp_AB (10–6 cm/s) | Papp_BA (10–6 cm/s) | Efflux Ratio | ||
| M4K2009 | 65a | 71a | 5.4a | 1.5a | 0.3a | 2.9 |
| M4K2286 (8) | 9.5 | 37.4 | 4.0 | 2.5 | 0.6 | 3.7 |
| M4K2277 (14) | 0.9 | 34.8 | 8.3 | 9.0 | 1.1 | 3.1 |
| M4K2207 (21) | 75.7 | 62.3 | 4.2 | 9.4 | 2.2 | 2.0 |
| M4K2303 (22) | 4.3 | 29.7 | 16.5 | 13.6 | 0.8 | 2.9 |
| M4K2308 (32) | 70.9 | 66.5 | 5.3 | 11.6 | 2.2 | 2.5 |
| M4K2281 (33) | 10.3 | 21.2 | 13.9 | 11.5 | 0.8 | 3.4 |
| M4K2304 (41) | 98.6 | 73.2 | 0.8e,f | 4.2e | 5.0 | 2.3 |
| M4K2306 (42) | 65.0 | 58.3 | 1.5e,f | 2.5e | 1.6 | 3.2 |
a
Literature values.10
b
Stability classification: stable (>70%), moderately stable (20–70%), unstable (<20%) compound remaining.
c
Permeability classification: low (Papp < 1), medium (Papp 1–3) or high (Papp > 3) × 10–6 cm/s.
d
Efflux ratio (BA/AB) classification: negative (ratio <2), minor/moderate (ratio 2–7) or high (ratio >7).
e
Average of duplicate measurements.
f
Poor post-assay recovery in A to B chambers possibly due to low aqueous solubility, high lipophilicity, nonspecific binding to plastics or cells, and/or poor intracellular stability of the test article.