Dual Binding Site and Selective Acetylcholinesterase Inhibitors Derived from Integrated Pharmacophore Models and Sequential Virtual Screening

Table 7

The binding scores, ADMET properties, and predicted AChE inhibitory IC₅₀ (nM) values of the top ranking conformers of the representative hits.

Number	ZINC codes	CNS	PSA	𝐴log𝑃	log𝐷	%HOA	Solu.	Derek*	IC50 (nM); AChE	IC50 (nM); BChE	GOLD; docking
1	ZINC04897936	2	18.77	4.78	3.60	100	−5.42	HERG	17.76	15197.5	58.43
2	ZINC04723800	0	70.71	4.35	4.35	100	−6.15	Nothing	22.56	16502.8	79.50
3	ZINC02375403	0	43.08	4.70	4.72	100	−6.45	Nothing	25.12	15648.3	73.16
4	ZINC03647721	2	19.32	4.88	3.77	100	−5.48	HERG	27.80	14942.8	66.23
5	ZINC09722585	0	47.10	4.02	4.02	100	−4.30	Nothing	28.02	15216.4	72.85
6	ZINC07982657	0	57.79	4.35	4.35	100	−5.29	Nothing	32.40	16209.0	72.27
7	ZINC04894394	1	40.68	4.28	4.16	100	−4.89	HERG	40.57	11729.1	70.81
8	ZINC09378344	0	43.04	4.31	4.32	100	−5.41	Nothing	48.08	15387.3	71.29
9	ZINC03437946	0	68.60	3.82	3.82	100	−4.79	Skin	49.23	15111.7	72.77
10	ZINC01038818	0	80.38	3.66	3.66	100	−5.74	Nothing	50.66	14830.6	74.69
11	ZINC09722179	0	42.58	4.30	4.30	100	−4.39	Nothing	53.62	14938.7	71.56
12	ZINC04677214	1	31.96	4.78	4.02	100	−5.56	HERG	57.70	14837.7	59.01
13	ZINC13006125	0	82.30	3.70	3.70	100	−4.44	Skin	62.18	14811.3	71.13
14	ZINC04678622	0	33.12	4.76	4.95	100	−5.73	Nothing	66.28	20416.1	70.05
15	ZINC11042835	0	62.81	4.34	4.34	100	−5.25	Nothing	66.42	14922.5	62.19
16	ZINC13007174	0	53.53	4.70	4.70	100	−5.41	Nothing	69.02	14835.2	68.24
17	ZINC09568866	0	73.19	4.74	4.74	100	−5.84	Nothing	79.39	14974.8	77.15
18	ZINC03326611	0	68.44	4.03	4.03	100	−4.42	Nothing	82.54	15048.3	69.16

∗HERG: HERG channel inhibition, Nothing: no toxicity, and Skin: skin sensitization.