Syntheses and spectroscopic characterization of some phosphoramidates as reversible inhibitors of human acetylcholinesterase and determination of their potency

Figures & data

Figure 1 The plot of V_I/V₀ against log ([I] × 10⁶) for inhibitors (Me₂N)P(O)(Cl)(p-NHC₆H₄NO₂), 1, and (Me₂N)P(O)(p-NHC₆H₄NO₂)₂, 2. V_I and V₀ are the enzyme activity (OD min^{− 1}) and [I] is the inhibitor concentration (μM).

Figure 2 The plot of V_I/V₀ against log ([I] × 10⁶) for inhibitors: 1-(p-CH₃C₆H₄O)P(O)(p-NHC₆H₄NO₂)₂, 3, 2-(p-CH₃C₆H₄O)₂P(O)(p-NHC₆H₄NO₂), 4. V_I and V₀ are the enzyme activity (OD min^{− 1}) and [I] is the inhibitor concentration (μM).

Scheme 1 The mechanism of human acetylcholinesterase inhibition by compounds 3 and 4.

Table I.  The spectral and enzymatic data for compounds 1–6.

Compound	δ31P (ppm)	^3JPNCH (Hz)	^7JP–H (Hz)	^nJP–C (Hz), (n=2–5)	νP = O (cm^− 1)	νPN (cm^− 1)	IC50 (mM)	Km × 10^5 (mol L^− 1)	Vmax × 10^6 (mol L^− 1min^− 1)	Ref.
1	− 0.9	s, 0	–	s, 0	1221	907 (ar) 724 (al)	^aNI	101.12	9.98	^b
2	2.17	s, 0	–	s, 0	1300	902 (ar) 746 (al)	^aNI	103.08	10.01	^b
3	− 19.09	–	s, 0	s, 0	1198	990	0.143	23.19	9.16	^b
4	− 17.64	–	s, 0	s, 0	1203	949	0.581	10.79	9.97	^b
5	–	d., 10	–	–	1250	980	–	–	–	27
6	–	–	–	–	1255	980	–	–	–	27

^a Non-Inhibitor.

^b This work.