Anticholinesterase activity of some major intermediates in carbacylamidophosphate synthesis: Preparation, spectral characterization and inhibitory potency determination

Figures & data

Table I.  The spectral and enzymatic data for compounds 1–4 where R is[C(O) NHP(O)Cl2].

Compound	νP(O) cm^− 1	νC(O) cm^− 1	νP–Cl cm^− 1	δ^31P ppm	IC50*μM	log(Po/w)	πx	ki (min^− 1)	Ki mM
CCl3R 1	1181	1736	590	8.08	5280 ± 120	− 0.09	1.17	0.056	9.74
CHCl2R 2	1194	1710	580	8.20	88 ± 22	− 0.48	0.78	0.31	0.036
CH2ClR 3	1125	1721	585	6.62	432 ± 35	− 0.87	0.39	0.169	0.206
CF3R 4	1180	1748	593	7.42	1030 ± 24	− 1.77	− 0.51	0.058	0.376

Scheme 1 Structures of compounds 1–4.

Figure 1 The plot of V_i/V_o against Log [I] × 10⁵ for inhibitor from 1 to 4: V_i and V_o are activity of enzyme in the presence and absence of inhibitor, respectively and [I] is inhibitor concentration (mol/lit), *means ± SE (n = 4).

Figure 2 Plots of ln (V_i/V_o) versus time (min) for inhibitors 1–4.

Scheme 2 Proposed mechanism for hAChE inhibition by compounds 1, 2, 3 and 4 following hydrolytic activation to RP(O)(OH)Cl, where R = CCl₃1, CHCl₂ 2, CH₂Cl 3, CF₃ 4.