Table 4. In silico ADME profiling of 3a–4x.

Compound	Absorption a				Distribution a
	Human intestinal absorption (HIA) (percentage)	In vitro Caco-2 cell permeability (nm s–1)	In vitro MDCK cell permeability (nm s–1)	In vitro skin permeability (log Kp, cm h–1)	In vitro plasma protein binding (percentage)	In vivo blood–brain barrier penetration (Cbrain/Cblood)
3a	98.05	21.25	5.33	–3.07	41.75	1.94
3b	98.02	9.30	58.36	–3.20	83.67	2.00
3c	98.00	20.72	45.82	–2.93	86.28	2.45
3d	98.00	21.50	21.61	–2.82	91.90	2.46
3e	98.01	22.03	7.14	–2.70	95.48	0.41
3f	98.06	22.88	0.41	–2.45	100.0	0.21
4a	99.01	21.06	80.91	–4.26	74.12	0.26
4b	99.01	20.55	5.15	–4.22	66.53	0.21
4c	98.95	21.62	0.05	–4.07	74.90	0.23
4d	98.85	22.24	0.04	–3.94	87.20	0.23
4e	98.73	21.28	0.09	–3.80	86.20	0.12
4f	98.42	24.17	149.0	–3.46	90.84	0.01
4g	98.62	21.18	2.65	–4.29	87.74	0.30
4h	98.46	21.22	0.74	–4.26	80.64	0.34
4i	98.30	21.56	0.05	–4.13	85.64	0.42
4j	98.14	21.95	0.04	–3.99	93.90	0.26
4k	98.00	22.52	0.06	–3.85	91.41	0.09
4l	97.76	24.44	73.79	–3.53	93.76	0.01
4m	99.01	21.16	3.09	–4.44	77.61	0.20
4n	99.00	20.40	3.46	–4.41	72.34	0.24
4o	98.94	21.48	0.06	–4.30	80.03	0.31
4p	98.84	22.09	0.04	–4.19	88.11	0.23
4q	98.72	21.70	0.07	–4.07	87.68	0.11
4r	98.41	25.00	72.17	–3.80	91.07	0.01
4s	98.09	21.23	0.15	–4.21	89.18	0.33
4t	97.95	21.40	0.06	–4.17	82.93	0.37
4u	97.83	21.68	0.02	–4.02	87.08	0.44
4v	97.73	22.07	0.03	–3.88	94.90	0.27
4w	97.65	22.64	0.02	–3.72	92.74	0.09
4x	97.56	24.33	0.46	–3.38	94.73	0.01

^aPredicted properties related to ADME using PreADMET using the web-based application PreADMET (http://preadmet.bmdrc.org).