Table 8 Pharmacokinetics and physicochemical properties prediction of pyrazole compounds

Physicochemical Properties

MW

420.16

397.1

447.12

552.19

385.15

327.11

Metabolism

CYP1A2-inh

0.344

0.867

0.677

0.169

0.943

0.931

Vol

446.047

400.215

455.569

570.244

395.769

335.091

CYP1A2-sub

0.097

0.07

0.059

0.077

0.925

0.052

Dense

0.942

0.992

0.981

0.968

0.973

0.976

CYP2C19-inh

0.714

0.951

0.851

0.517

0.578

0.886

nHA

6

6

6

9

7

6

CYP2C19-sub

0.071

0.064

0.06

0.064

0.346

0.048

nHD

1

1

1

1

1

2

CYP2C9-inh

0.954

0.95

0.966

0.876

0.673

0.894

TPSA

79.94

86.83

86.83

114.21

79.59

90.26

CYP2C9-sub

0.849

0.442

0.112

0.77

0.079

0.965

nRot

7

5

5

8

4

3

CYP2D6-inh

0.03

0.483

0.093

0

0.001

0.594

nRing

4

4

5

6

4

4

CYP2D6-sub

0.539

0.094

0.063

0.422

0.094

0.219

MaxRing

6

6

9

10

6

6

CYP3A4-inh

0.579

0.619

0.591

0.18

0.135

0.707

nHet

6

7

7

9

7

6

CYP3A4-sub

0.763

0.533

0.721

0.704

0.46

0.194

fChar

0

0

0

0

0

0

Excretion

CL (Clearance)

7.504

5.581

4.283

1.622

5.135

4.876

nRig

26

26

31

38

26

24

T12

0.086

0.178

0.058

0.044

0.044

0.282

Flex

0.269

0.192

0.161

0.211

0.154

0.125

Toxicity

hERG Blockers

0.057

0.02

0.008

0.064

0.027

0.03

nStereo

0

0

0

0

0

0

H–HT

0.847

0.988

0.991

0.96

0.746

0.975

Solubility

LogS

−6.972

−5.685

−6.75

−9.21

−4.963

−5.236

DILI

0.992

0.997

0.997

0.993

0.996

0.997

LogD

4.276

4.087

4.587

4.438

3.008

3.026

AMES Toxicity

0.256

0.065

0.16

0.239

0.066

0.11

LogP

5.083

4.065

5.193

7.171

3.486

2.93

Rat Oral Acute Toxicity

0.271

0.38

0.187

0.042

0.227

0.023

ESOL Log S

−2.45

−2.99

−2.18

−2.75

−3.12

−2.44

FDAMDD

0.92

0.934

0.908

0.921

0.961

0.836

Ali Log S

−6.111

−6.210

−7.400

−7.321

−6.210

−6.210

Skin Sensitization

0.054

0.044

0.031

0.326

0.041

0.097

Silicon-IT class

Soluble

Soluble

Soluble

Soluble

Soluble

Soluble

Carcinogenicity

0.302

0.057

0.592

0.797

0.177

0.046

Drug-likeness

Lipinski Rule

Accepted

Accepted

Accepted

Rejected

Accepted

Accepted

Eye Corrosion

0.003

0.003

0.003

0.003

0.003

0.003

Pfizer Rule

Accepted

Accepted

Accepted

Accepted

Accepted

Accepted

Eye Irritation

0.279

0.175

0.489

0.227

0.019

0.68

Golden Triangle

Accepted

Accepted

Accepted

Rejected

Accepted

Accepted

Respiratory Toxicity

0.146

0.804

0.298

0.057

0.801

0.954

Absorption

Pgp-inh

0.996

0.841

0.966

0.998

0.951

0.857

Toxicophoric rules

N-G Carcinogenicity

0

0

0

0

0

0

Pgp-sub

0

0

0

0.002

0

0

LD50_oral

0

0

0

0

0

0

HIA

0.022

0.645

0.047

0.014

0.007

0.015

Genotoxic Carcinogenicity

1

0

0

6

1

0

F (20%)

0.006

0.025

0.007

0.447

0.002

0.002

Sure ChEMBL

0

0

0

1

0

0

F (30%)

0.006

0.01

0.006

0.993

0.003

0.001

Non-Biodegradable

0

0

0

1

2

0

Caco-2

−5.025

−4.844

−4.962

−4.852

−4.659

−5.407

Skin Sensitization

5

1

1

1

1

0

MDCK

8.21E-06

1.63E-05

1.13E-05

1.30E-05

2.27E-05

1.08E-05

Aquatic Toxicity Rule

4

3

3

1

3

0

Distribution

BBB

0.131

0.284

0.26

0.002

0.51

0.262

Medicinal Chemistry

Toxicophores

4

4

4

6

4

2

PPB

99.93%

98.67%

99.88%

107.22%

97.59%

98.63%

QED

0.348

0.418

0.307

0.098

0.552

0.606

VDss

0.603

0.418

0.515

1.222

0.579

0.416

Synth

2.141

3.009

2.823

2.759

2.774

2.532

Fu

0.82%

0.68%

0.53%

0.53%

1.47%

1.54%

Fsp3

0.038

0

0

0.03

0.091

0