Table 8. ADMET Properties Predicted for Compounds 4a–l.
| entry | human intestinal absorption (HIA, %)a | in vitro Caco-2 cell permeability (nm/sec)b | in vitro MDCK cell permeability (nm/sec)c | in vitro skin permeability (logKp, cm/hour)d | in vitro plasma protein binding (%)e | in vivo blood–brain barrier penetration (C.brain/C.blood)f | toxicityg |
|---|---|---|---|---|---|---|---|
| 4a | 86.3824 | 1.3408 | 26.8358 | –3.7287 | 82.6676 | 0.2629 | negative |
| 4b | 75.6539 | 0.4007 | 21.2933 | –4.1593 | 83.0199 | 0.1383 | negative |
| 4c | 64.2959 | 0.3780 | 32.3669 | –3.6705 | 99.0693 | 0.1129 | negative |
| 4d | 65.52749 | 0.3749 | 10.6479 | –4.4693 | 73.3206 | 0.3142 | negative |
| 4e | 44.9103 | 0.3733 | 1.5565 | –3.5385 | 84.2593 | 0.0980 | negative |
| 4f | 28.6676 | 0.3736 | 0.8129 | –3.8568 | 81.0702 | 0.0685 | negative |
| 4g | 20.0169 | 0.3695 | 0.7395 | –3.5409 | 99.7054 | 0.0593 | negative |
| 4h | 20.8803 | 0.3673 | 1.2663 | –4.1431 | 67.6284 | 0.3162 | negative |
| 4i | 92.1140 | 18.2471 | 69.1110 | –2.9966 | 100.0000 | 0.4244 | negative |
| 4j | 85.3032 | 5.3632 | 52.2455 | –3.3667 | 100.0000 | 0.2141 | negative |
| 4k | 76.8665 | 1.4893 | 10.7085 | –3.1303 | 100.0000 | 0.1683 | negative |
| 4l | 76.0095 | 1.1041 | 82.9175 | –3.8803 | 97.1879 | 0.1495 | negative |
a
HIA is the sum of bioavailability and absorption evaluated from the ratio of excretion or cumulative excretion in urine, bile, and feces.
b
Caco-2 cells are derived from human colon adenocarcinoma and possess multiple drug transport pathways through the intestinal epithelium.
c
MDCK cell system is used as a tool for rapid permeability screening.
d
The in vitro skin permeability infers the transdermal drug delivery property.
e
The percent of drug binds to plasma protein.
f
Blood–brain barrier (BBB) = [brain]/[blood].
g
In vitro Ames test by metabolic and non-metabolic activated TA100 and TA1535 strains collected from rat liver homogenate.