Table 2.

Predicted pharmacokinetic and pharmacodynamic properties of the 14 hit 2,5-diphenyloxazole derivatives.

Parameter	Compound
	1	3	4	7	9	10	12	31	32	40	42	44	47	48	Chloroquine	Artemisinin	Desired value
Molecular Weight (g/mol)	269.26	395.37	269.26	253.26	337.33	285.26	453.4	297.31	387.44	285.32	270.24	286.31	269.26	401.42	319.87	282.336	≤500
No. H-bond acceptors	5	8	5	4	6	6	10	5	5	4	6	5	5	8	2	5	≤10
No. H-bond donors	3	0	3	2	0	4	0	1	0	3	3	3	3	0	1	0	≤5
No. rotatable bond (rotors)	2	8	2	2	6	2	10	4	7	2	2	2	2	8	8	0	≤10
Topological polar surface area (TPSA, Å2)	86.72	104.93	86.72	66.49	78.63	106.95	131.27	64.72	53.72	101.82	99.61	114.71	86.72	81.41	28.16	53.99	≤140
Lipophilicity Log P octanol/water partition coefficient	2.25	3.14	2.3	2.65	3.3	1.89	3.12	2.98	4.52	2.89	1.9	2.48	2.27	3.34	4.15	2.5	≤5
Water solubility Log S (ESOL) solubility class	−3.64 soluble	−4.04 moderately soluble	−3.64 soluble	−3.80 soluble	−4.04 moderately soluble	−3.49 soluble	−4.05 moderately soluble	−4.04 moderately soluble	−5.56 moderately soluble	−4.13 moderately soluble	−3.28 soluble	−3.76 soluble	−3.64 soluble	−4.43 mederately soluble	−4.55 moderately soluble	−3.42 soluble	Insoluble < −10 < Poorly < −6 < Moderately < −4< Soluble < −2 Very <0< Highly
Metabolism
CYP2D6 substrate	No	No	No	No	No	No	No	No	No	No	No	No	No	No	Yes	No
CYP3A4 substrate	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
CYP1A2 inhibitor	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	No
CYP2C19 inhibitor	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes	no	No	No
CYP2C9 inhibitor	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	No
CYP2D6 inhibitor	No	No	No	No	No	No	No	No	No	No	No	No	No	No	Yes	No
CYP3A4 inhibitor	Yes	No	Yes	No	No	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	No	No
Intestinal absorption (% absorbed)	90.247	92.839	90.158	91.24	97.454	84.212	100	94.32	97.685	89.598	80.473	89.912	90.636	97.545	89.95	97.543	≥30%
Total clearance (log ml/min/kg)	0.348	0.749	0.437	0.617	0.851	0.593	1.207	0.57	0.672	0.303	0.007	0.264	0.406	0.838	1.092	0.98
BBB permeant	No	No	No	Yes	No	No	No	Yes	Yes	No	No	No	No	No	Yes	Yes
LD50 oral rat acute toxicity (mol/kg)	2.358	2.628	2.492	2.409	2.703	2.475	3.149	2.333	2.515	2.328	2.26	2.297	2.375	2.515	2.85	2.459
Hepatoxicity	No	Yes	No	No	Yes	No	Yes	No	Yes	No	No	No	No	Yes	Yes	No
AMES toxicity (act as a carcinogen)	No	No	No	No	No	No	No	No	No	No	No	No	No	No	Yes	Yes
Max tolerated dose in human (log ml/min/kg)	0.271	0.555	0.268	0.293	0.671	0.752	0.741	0.136	0.78	0.295	0.315	0.323	0.214	0.833	−0.167	0.065	≥0.477 high tolerance
Drug likeness
Lipinski (Pfizer)	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Ghose	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Veber (GSK)	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Egan (Pharmacia)	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Abbott Bioavailability Score	0.55	0.55	0.55	0.55	0.55	0.55	0.55	0.55	0.55	0.55	0.55	0.55	0.55	0.55	0.55	0.55
Synthesis accessibility score	2.92	3.48	2.92	2.9	3.27	2.99	3.74	3.12	3.67	2.84	2.71	2.82	2.79	3.75	2.75	6.13	from 1 (very easy) to 10 (very difficult)