Table 2.

Calculated physicochemical and ADME-Tox properties of the synthesized compounds 5–10 in addition to griseofulvin (1) and compound 3.

ADME-Tox	1	3	5	6	7	8	9	10
Solubility (log⁡S)	−3.96	−5.52	−1.31 [pH = 6.8]	−3.25	−3.03 [pH = 6.8]	−3.85 [pH = 6.8]	−4.39	−4.13 [pH = 6.8]
			−4.81 [pH = 1.2]		−1.48 [pH = 1.2]	−1.99 [pH = 1.2]		−2.59 [pH = 1.2]
F (%)a	30–70% (0.637)	30–70% (0.637)	<30% (0.589)	30–70% (0.541)	30–70% (0.541)	30–70% (0.541)	30–70% (0.541)	30–70% (0.541)
HIA (%)b	100%	100%	100%	100%	78%	100%	100%	100%
Pe (cm/s)c	7.91 × 10−4	7.36 × 10−4	5.95 × 10−4	6.59 × 10−4	0.46 × 10−4	7.15 × 10−4	7 × 10−4	3.33 × 10−4
log⁡BBd (log⁡PS)e	0.1	0.03	−0.55	−0.32	0.02	0.01	−0.28	−0.06
	(−1.4)	(−1.2)	(−2.6)	(−2.4)	(−3.5)	(−1.5)	(−1.7)	(−2.8)
pKa	—	—	2.80	—	9.50	3.60	—	9.50
LD50 mouse (mg kg−1, oral)	1000	1100	1300	810	560	850	1100	700
LD50 mouse (mg kg−1, intraperitoneal)	180	190	470	440	200	440	460	240
LD50 mouse (mg kg−1, intravenous)	100	62	96	10	25	130	54	21
LD50 mouse (mg kg−1, subcutaneous)	330	140	820	470	67	110	340	62
log⁡Pf	2.51	3.79	3.96	2.02	1.93	3.35	3.67	3.55
TPSA (Å2)g	8.06	8.06	112.88	121.47	128.25	108.34	121.47	128.25
MWh	352.77	428.86	501.91	409.82	408.84	48.89	485.92	484.94
NOHDi	0	0	1	3	4	1	3	4
NOHAj	6	6	9	9	9	9	9	9
NORBk	3	5	8	4	5	5	6	7

^aHuman oral bioavailability (probability). ^bHuman intestinal absorption. ^cPermeability (human jejunum). ^dExtent of blood brain barrier penetration. ^eRate of brain penetration. ^fCalculated lipophilicity. ^gTopological polar surface area. ^hMolecular weight. ⁱNumber of hydrogen bond donors. ^jNumber of hydrogen bond acceptors. ^kNumber of rotatable bonds.