Table 3. In Silico Physicochemical, Pharmacokinetic, and Drug-likeness Parameters of 3b, 3c, and 3f.

type of parameter	parameter	3b	3c and 3f
physicochemical properties	M.W. (g/mol)a	254.26	270.72
	N° rotatable bonds	2	2
	N° H-bond acceptors	4	3
	N° H-bond donors	2	2
	molar refractivity	72.14	77.19
	TPSA (Å2)b	63.83	63.83
lipophilicity	log Po/w (iLOGP)	2.35	2.07
	log Po/w (XLOGP3)	3.18	3.71
	log Po/w (WLOGP)	2.95	3.05
	log Po/w (MLOGP)	3.19	3.31
	log Po/w (SILICOS-IT)	2.33	2.55
	consensus log Po/w	2.80	2.94
water solubility	log S (ESOL)	–3.91	–4.35
	solubility	123 μM (soluble)	45 μM (moderately soluble)
	log S (Ali)	–4.19	–4.74
	solubility	64.3 μM (moderately soluble)	18.1 μM (moderately soluble)
pharmacokinetic properties	GI absorptionc	high	high
	BBB permeantd	yes	yes
	P-gp substratee	no	no
	CYP1A2 inhibitor	yes	yes
	CYP2C19 inhibitor	yes	yes
	CYP2C9 inhibitor	no	no
	CYP2D6 inhibitor	no	no
	CYP3A4 inhibitor	no	no
	log Kp (skin permeation)	–5.59 cm/s	–5.32 cm/s
drug-likeness	Lipinski	fit; 0 violation	fit; 0 violation
	Ghose	fit	fit
	Veber	fit	fit
	Egan	fit	fit
	Muegge	fit	fit
	bioavailability score	0.55	0.55
medicinal chemistry	PAINS	0 alert	0 alert
	Brenk	1 alerts: hydrazine	1 alert: hydrazine
	lead-likeness	fit	do not fit; 1 violation: XLOGP3 > 3.5

^aMW: molecular weight.

^bTPSA: topological polar surface area.

^cG.I.; gastrointestinal.

^dBBB: blood–brain barrier.

^eP-gp: P-glycoprotein. Drug-likeness maps are found in Figure S3.