Synthesis and inhibitory properties of some carbamates on carbonic anhydrase and acetylcholine esterase

Figures & data

Figure 1. Some selected carbamate drugs.

Scheme 1. The synthesis of acid 7 and carbamates 10–12 (i) TFA, Et₃SiH, 75 °C, 4 h (ii) NaOH, MeOH-H₂O, 25 °C, 4 h (iii) NEt₃, DPPA, 80 °C, 4 h, then BnOH, 80 °C, 30 h.

Figure 2. Carbamates 13 and 14, sulfamoyl carbamates 15 and 16.

Table 1. Human carbonic anhydrase isoenzymes (hCA I and II) and acetylcholine esterase (AChE) inhibition profile of carbamate derivatives (10–16).

	IC50 (nM)							Ki (nM)
Compounds	hCA I	r^2	hCA II	r^2	AChE	r^2	hCA I	hCA II	AChE
10	53.32	0.9844	7.24	0.9787	72.05	0.9725	5.61 ± 1.52	7.39 ± 2.66	0.261 ± 0.099
11	54.54	0.9802	89.79	0.9641	7.91	0.9622	5.41 ± 1.59	7.66 ± 2.73	0.286 ± 0.085
12	49.65	0.9808	157.00	0.9617	7.92	0.9679	5.51 ± 1.30	7.48 ± 2.23	0.291 ± 0.105
13	30.58	0.9845	44.69	0.9728	20.39	0.9737	4.91 ± 1.68	6.93 ± 2.49	0.265 ± 0.083
14	69.73	0.9861	6.98	0.9530	7.70	0.9693	5.89 ± 1.65	7.39 ± 2.74	0.264 ± 0.095
15	19.41	0.9865	13.43	0.9630	24.53	0.9709	4.49 ± 1.32	4.94 ± 1.76	0.209 ± 0.069
16	23.50	0.9874	21.89	0.9745	9.66	0.9676	4.59 ± 1.35	5.78 ± 1.78	0.240 ± 0.097
AZA*	8.26	0.9654	8.93	0.9676	-	-	281.33 ± 55.33	9.07 ± 2.68	-
TAC**	-	-	-	-	57.52	0.9721	-	-	0.398 ± 0.103

*Acetazolamide (AZA) was used as a standard inhibitor for CA I and II.

**Tacrine (TAC) was used as a standard inhibitor for AChE.