New N,N-dimethylcarbamate inhibitors of acetylcholinesterase: design synthesis and biological evaluation

Figures & data

Chart 1. Main AChEIs approved for the treatment of AD.

Chart 2. Synthesized carbamates 1–14.

Scheme 1. Synthetic routes to carbamates 1–14.

Table 1. AChE inhibition activity of synthesized carbamates 1–14 and alcohol 15d. The data represent the inhibition percentage at different inhibitor concentration (see experimental).

				Inhibition %
Compound	R	R^1	n	at 50 μM	at 25 μM	at 12.5 μM
1	H	CON(CH3)2	1	57	–	–
2	H	CON(CH3)2	2	41	36	–
3	H	CON(CH3)2	3	60	–	–
4	H	CON(CH3)2	4	85	–	–
5	CH3	CON(CH3)2	1	–	8	–
6	CH3	CON(CH3)2	2	–	27	–
7	CH3	CON(CH3)2	3	26	–	–
8	CH3	CON(CH3)2	4	69	–	–
9	F	CON(CH3)2	1	–	–	25
10	F	CON(CH3)2	2	13	–	–
11	F	CON(CH3)2	4	12	–	–
12	CF3	CON(CH3)2	1	31	–	–
13	CF3	CON(CH3)2	2	7	–	–
14	CF3	CON(CH3)2	4	31	–	–
15d	H	H	4	32

Figure 1. Best binding pose of compound 4 (light blue colored) in the active site of TcAChE (1EVE). The selected amino acids are orange colored.