Table 3.

Pharmacokinetic- and toxicity-evaluated parameters of compounds reported in Table 1 ^a,b.

Compound		1	2	3	4	5	6	7	8	9	10
Absorption	Caco-2 permeability	−0.229	−0.229	0.738	−0.136	0.892	0.833	0.226	−0.193	0.244	0.781
	Human intestinal absorption	72.208	72.208	95.203	72.88	94.924	94.829	80.162	65.507	75.034	95.909
	Skin permeability	−2.735	−2.735	−3.318	−2.855	−2827	−2.777	−2.735	−2.915	−2.763	−3.461
Distribution	VDss (human)	0.444	0.444	−0.165	−1.026	0.129	−0.283	0.213	−0.386	−0.008	−0.147
	Fraction unbound (human)	0.736	0.736	0.335	0.425	0.408	0.094	0.705	0.151	0.367	0.323
	BBB permeability	−1.378	−1.378	−0.208	−1.425	−0.279	−0.172	−1.334	−0.941	−0.734	−0.67
	CNS permeability	−3.874	−3.874	−2.518	−2.913	−2.447	−2.607	−3.363	−3.062	−2.963	−3.207
Excretion	Total clearance	0.644	0.644	0.515	−0.058	0.498	0.582	0.647	0.226	0.552	1.141
	Renal OCT2 substrate c	No	No	No	No	No	No	No	No	No	No
Toxicity	Skin sensitization	No	No	No	No	No	No	No	No	No	No
	AMES toxicity	No	No	No	Yes	Yes	Yes	No	No	No	Yes
	Oral rat acute toxicity (LD50)	2.275	2.275	0.874	2.984	2.368	2.512	2.401	2.852	2.862	2.774
	Minnow toxicity	3.169	3.169	2.94	1.987	2.437	−0.023	4.045	−0.275	2.108	−0.42

^a All results were obtained from the pkCSM webserver [44]. ^b Semaphore flags: green = excellent, yellow = discrete, red = insufficient. ^c Unimportant, because the total clearance is high, with the exception of compound 4.