Table 5.

Predicted absorption-distribution-metabolism- excretion (ADME) parameters and drug-like properties of compound 36 and the newly designed inhibitors (N1–3).

Properties	Parameters	Compounds
		36	N1	N2	N3
Physicochemical	MWa (g/mol)	532.66	482.58	481.59	482.57
Properties	Rotatable bonds	7	11	10	10
	HBA	8	8	7	8
	HBD	2	3	2	2
	TPSAb	142.61	133.91	121.88	116.09
Lipophilicity	iLOGP	3.82	3.29	3.38	3.60
	XLOGP3	4.17	0.04	0.92	1.57
	WLOGP	4.33	0.63	1.72	2.32
	MLOGP	2.06	0.44	1.42	1.82
	Silicos IT logP	3.51	2.08	3.09	3.33
	Consensus logP	3.58	1.30	2.11	2.53
Water Solubility	ESOL Class	MSc	Sd	S	S
	Ali Class	PSe	S	S	S
	Silicos IT Class	PS	MS	MS	MS
Pharmacokinetics	GIf absorption	low	high	high	high
	BBBg permeat	No	No	No	No
	CYP1A2 inhibitor	No	No	No	No
	CYP2C19 inhibitor	Yes	No	No	No
	CYP2C9 inhibitor	Yes	No	No	No
	CYP2D6 inhibitor	Yes	No	Yes	Yes
	CYP3A4 inhibitor	Yes	No	Yes	Yes
Druglikeness	Lipinski violations	1	0	0	0
	Ghose violations	2	2	2	2
	Egan violations	1	1	0	0
	Muegge violations	1	1	0	0
	Bioavailability Score	0.55	0.55	0.55	0.56
Medicinal Chemistry	PAINSh alerts	0	0	0	0
	Brenk alerts	0	1	0	0
	Leadlikeness violations	2	2	1	2
	Synthetic accessibility	4.68	4.68	4.12	4.10

^aMolecular weight.

^bTotal polar surface area.

^cModerately soluble.

^dSoluble.

^ePoorly soluble.

^fGastrointestinal.

^gBlood–brain barrier.

^hPan assay interference compounds.