Table 9 Pharmacokinetics of compounds 13 and 21

Absorption

Caco2 permeability

0.823

1.035

Intestinal absorption (human)

91.939

86.102

Skin Permeability

 − 2.738

 − 2.735

Distribution

Volume of distributions

1.411

0.932

Fraction unbound (human)

0.183

0.082

BBB permeability

 − 0.024

 − 0.001

CNS permeability

 − 2.192

 − 2.168

Metabolism

CYP2D6 substrate

Yes

Yes

CYP3A4 substrate

Yes

Yes

Excretion

Total Clearance

0.623

0.906

Renal OCT2 substrate

Yes

Yes

Toxicity

AMES toxicity

Yes

Yes

Oral rat acute toxicity (LD50)

2.919

2.723

Minnow toxicity

 − 0.674

0.257