Design, Synthesis, and Acetylcholinesterase Inhibition Assay of Novel 9-(1-(Substituted-benzyl)piperidin-4-yl)-2-chloro-9H-purin-6-amine Derivatives

Table 1

Cholinesterase inhibition activity of 9-(1-(substituted-benzyl)piperidin-4-yl)-2-chloro-9H-purin-6-amine derivatives^a.

Compd.	Ar	R1	Cholinesterase inhibition % at 100 𝜇M
7a1	3,4-Dimethoxyphenyl	3-Chlorobenzyl	11.03
7a2	3,4-Dimethoxyphenyl	3-bromobenzyl	0.24
7a3	3,4-Dimethoxyphenyl	4-Cyanobenzyl	0.47
7a4	3,4-Dimethoxyphenyl	4-Nitrobenzyl	3.84
7a5	3,4-Dimethoxyphenyl	3-Fluorobenzyl	3.48
7a6	3,4-Dimethoxyphenyl	Pyridine-4-yl-methyl	NA^b
7a7	3,4-Dimethoxyphenyl	Benzyl	14.57
7a8	3,4-Dimethoxyphenyl	4-Bromobenzyl	NA
7a9	3,4-Dimethoxyphenyl	3-Cyanobenzyl	6.10
7a10; 7a11	3,4-Dimethoxyphenyl; 3,4-Dimethoxyphenyl	4-Methoxybenzyl; 2,6-Dicholobenzyl	NA; NA
7a12	3,4-Dimethoxyphenyl	2,4,6-Trimethylbenzyl	NA
7a13	3,4-Dimethoxyphenyl	2-Fluorobenzyl	4.02
7b1	Benzo[d][1,3]dioxol-5-yl	3-Chlorobenzyl	NA
7b2	Benzo[d][1,3]dioxol-5-yl	3-Bromobenzyl	0.09
7b3	Benzo[d][1,3]dioxol-5-yl	4-Cyanobenzyl	NA
7b4	Benzo[d][1,3]dioxol-5-yl	4-Nitrobenzyl	NA
7b5	Benzo[d][1,3]dioxol-5-yl	3-Fluorobenzyl	0.14
7b6	Benzo[d][1,3]dioxol-5-yl	Pyridine-4-yl-methyl	NA
7b7	Benzo[d][1,3]dioxol-5-yl	Benzyl	7.55
7b8	Benzo[d][1,3]dioxol-5-yl	4-Bromobenzyl	7.29
7b9	Benzo[d][1,3]dioxol-5-yl	3-Cyanobenzyl	15.42
7b10	Benzo[d][1,3]dioxol-5-yl	4-Methoxybenzyl	11.21
7b11	Benzo[d][1,3]dioxol-5-yl	2,6-Dicholobenzyl	3.80
7b12	Benzo[d][1,3]dioxol-5-yl	2,4,6-Trimethylbenzyl	1.51
7b13	Benzo[d][1,3]dioxol-5-yl	2-Fluorobenzyl	6.14
Donepezil			80.07

aSee the experimental section for assay details. bNot active.