Tabel 3.

ADMET profile of the three (5b, 5c, 5d) most active compounds and diclofenac sodium.

Parameter	5b	5c	5d	Diclofenac Sodium
Molecular properties
Molecular Weight	255.704	237.258	237.258	318.135
LogP	4.662	3.7142	3.7142	3.9062
Rotatable Bonds	2	2	2	4
Acceptors	2	3	3	3
Donors	0	1	1	1
Surface Area	109.814	104.305	104.305	144.12
Absorption
Water solubility	−4.694	−3.174	−3.264	−4.497
Caco2 permeability	1.043	1.323	1.301	1.121
Intestinal absorption (human)	95.242	94.292	94.444	94.028
Skin Permeability	−2.592	−2.733	−2.736	−2.846
P-glycoprotein substrate	No	No	No	No
P-glycoprotein I inhibitor	No	No	No	No
P-glycoprotein II inhibitor	Yes	Yes	Yes	No
Distribution
VDss (human)	0.221	0.019	−0.111	0.224
Fraction unbound (human)	0.183	0.174	0.161	0.102
BBB permeability	0.184	0.016	0.355	0.254
CNS permeability	−1.365	−1.366	−1.437	−1.115
Metabolism
CYP2D6 substrate	No	No	No	No
CYP3A4 substrate	Yes	No	No	No
CYP1A2 inhibitior	Yes	Yes	Yes	Yes
CYP2C19 inhibitior	Yes	Yes	Yes	Yes
CYP2C9 inhibitior	Yes	Yes	Yes	Yes
CYP2D6 inhibitior	No	No	No	No
CYP3A4 inhibitior	No	No	No	Yes
Excretion
Total Clearance	0.23	0.357	0.343	1.116
Renal OCT2 substrate	No	No	No	No
Toxicity
AMES toxicity	No	Yes	Yes	No
Max. tolerated dose (human)	0.577	0.724	0.697	No
hERG I inhibitor	No	No	No	0.521
hERG II inhibitor	Yes	Yes	Yes	No
Oral Rat Acute Toxicity (LD50)	2.231	2.213	2.096	2.620
Oral Rat Chronic Toxicity (LOAEL)	0.885	1.708	1.768	0.966
Hepatotoxicity	No	No	No	No
Skin Sensitization	No	No	No	No
T.Pyriformis toxicity	0.493	0.466	0.469	1.397
Minnow toxicity	−0.606	0.466	0.605	−2.43