Table 4. In Vitro and In Vivo ADME Profile of Lead Compounds.
| MDCK
(10–6 cm/s) |
Hepatocytes
(μL/min/106 cells) |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Entry | Caco2 A to B Papp (10–6 cm/s) | AB/BA | Efflux ratio | Rat | Human | HLM (μL/min/mg) | PSA | Bioavailability (%)/CL (mL/min/kg)/Vss (L/kg)a | Kp,uu | MPO scoreb |
| 27 | 97.1 | 3.44/22.4 | 6.51 | 14.8 | 1.81 | 5.01 | 78 | 57/74/4.3 | 0.11 | 5.0 |
| 25 | 51.6 | 0.740/25.6 | 34.6 | 5.13 | 2.48 | <3.00 | 97 | 96/3.0/1.5 | 0.014 | 4.5 |
| 29 | 64.1 | 3.60/14.2 | 3.94 | 5.99 | 4.27 | 12.2 | 78 | 100/60/4.6 | 0.10 | 4.7 |
| 31 | 73.9 | 2.04/37.9 | 18.6 | 4.81 | 1.29 | <3.00 | 88 | 91/13/1.6 | 0.022 | 5.2 |
a
Averaged data from 2 male Han Wistar rats per dose group (see Supporting Information for further details).
b
Score for the CNS MPO algorithm as defined by Wager et al.