Table 3 Predicted physicochemical parameters and ADMET properties of SMs (1–4, 6)

Physicochemical properties

MW^a (g/mol)

111.10

207.23

145.16

372.42

265.30

Rotatable bonds

1

0

1

4

5

HBA^b

2

3

1

2

5

HBD^c

2

1

1

4

2

Fraction Csp3

0.00

0.55

0.00

0.18

0.50

TPSA^d

53.09

43.77

32.86

89.78

67.79

Lipophilicity Log P_o/w

iLOGP

0.70

1.79

1.12

1.91

2.34

XLOGP3

0.85

−0.20

1.93

2.93

0.90

MLOGP

−0.36

0.95

0.88

1.43

0.71

Absorption

Water solubility (mol/L)

−2.059

−2.457

−1.948

−3.212

−1.417

Caco2 permeability (10⁻⁶ cm/s)

1.127

1.2

1.622

0.88

0.471

Intestinal absorption (human) (% absorbed)

88.64

86.19

93.376

94.30

74.969

Skin permeability (log/kp)

−2.735

−3.803

−2.352

−2.736

−2.824

P-glycoprotein substrate

No

No

No

Yes

No

Distribution

VDs (human)

−1.027

0.243

0.02

−0.011

0.391

BBB permeability (log BB)

−0.389

−0.158

0.413

−0.596

−0.24

CNS permeability (log PS)

−2.946

−2.996

−1.666

−2.301

−2.871

Metabolism

CYP1A2 inhibitor

No

No

Yes

Yes

No

CYP2C19 inhibitor

No

No

No

Yes

No

CYP2C9 inhibitor

No

No

No

Yes

No

CYP2D6 inhibitor

No

No

No

No

No

CYP3A4 inhibitor

No

No

No

Yes

No

Excretion

Total clearance (log ml/min/kg)

0.662

0.441

0.449

0.734

0.956

Renal OCT2 substrate

No

No

Yes

No

No

Toxicity

Max tolerated dose (log /mg/kg/day)

0.778

0.673

0.397

0.198

-0–115

hERG I inhibitor

No

No

No

No

No

hERG II inhibitor

No

No

No

Yes

No

Oral Rat Acute toxicity LD50, (mol/kg)

2.206

1.975

2.307

2.763

2.681

Hepatotoxicity

No

No

No

No

No

Skin sensatisation

No

No

Yes

No

No

T. Pyriforms toxicity (log ug/L)

0.247

0.168

0.255

0.297

0.269

Minnow toxicity (log mM)

2.812

1.95

0.716

1.275

1.471