Structure, reactivity, and biological activity of O-(diethyl phosphoryl)oximes and O-(methylcarbamoyl)oximes of substituted acetophenones and .alpha.-substituted benzaldehydes

Abstract

a n d R. 0. M y e r s A series of 0-(diethyl phosphoryl) and 0-(methyl-carbamoy1)oximes of substituted acetophenones and a-substituted benzaldehydes were evaluated for anticholinesterase activity, toxicity to insects, and for chemical reactivity. Multiple regression analysis was used to correlate reactivity and biological data with free energy parameters. Excellent correlation was obtained between electronic effects, reactivity and anticholinesterase activity for the ring-substituted acetophenone 0-(diethyl phosphory1)oximes and 0-(methylcarbamoy1)oximes. With the a-substituted benzaldehyde 0-(methylcarbamoy1)oximes. the addition of Hansch's K constant to the regression equation was necessary to provide correlation with anticholinesterase activity. An unusual example of the Beckmann rearrangement was discovered and the high reactivity of substituted acetophenone @(diethyl phosphory1)oximes containing electrondonating substituents is explained in terms of this rearrangement.ince the report by Hackley er a/. (1959) describing the potent anticholinesterase activity and toxicity of 0-(iso-

Synthesis and Quantitative of Structure-Activity Relationships of Phosphoramidates and Phosphorodiamidates Incorporating Amino Acid Esters

“…It was reported that the hydrophobicity parameter (n) improved the correlation of anticholinesterase activity with the electronic parameters and played an important role in the inhibition process. 24 The above results showed the importance of both the reactivity of these compounds and their steric interaction with the AChE active site in controlling the enzyme inhibition as presented below. …”

Synthesis and bioactivity ofO-ethyl phosphorodiamidates derived from quinazolin-4-ones and either amino acid esters or fatty amines

“…According to equation 1, the toxicity of the compound is directly proportional to the electron withdrawing ability of aryl substituents, which explains the high toxicity of compounds containing a nitro group. This field effect can be attributed to the enhancement of the electrophilicity of the neighboring carbonyl carbon that can participate in interaction with acetylcholinesterase enzyme of the mosquito larvae; it was reported by Fukuto et al [15] that there is an excellent correlation between toxicity (LC 50 ) to mosquito larvae and anticholinesterase activity of some organophosphates and carbamoyloximes. Equation 1 also indicates that the toxicity of the compound is reduced by increasing the steric effect of ␣-alkyl groups of amino acid moieties and enhanced by the electron donating ability of the same groups.…”

“…In the amino acid ester derivatives (6)(7)(8)(9)(10)(11)(12)(13)(14), the proton signals of the two ethyl groups are overlapped. However, in fatty amine derivatives (15)(16)(17)(18)(19)(20)(21)(22), the methylene proton signal of the O-ethyl phosphorodiamidates did not interfere with other signals and appeared as a doublet of quartets with coupling constants J H-P ϳ20 Hz and J H-H ϳ6 Hz. Other features of the spectra of the fatty amine derivatives are similar to those of the amino acid derivatives listed in Table 2 except for the presence of a multiplet of the N-CH 2 protons at d ϳ2.9 ppm and a large multiplet at d ϳ1.02 ppm for other aliphatic protons.…”

“…It was found that some formulated organophosphorus pesticides such as chlorpyrifos and sumithion achieved a mosquito larvae mortality level of 90-100% after a period of 48-85 days posttreatment [13]. It was also reported that 4-substituted 3,5-xylenyl diethyl phosphates [14], substituted acetophenone and benzaldehyde O-(diethyl phosphoryl) oxime [15], and some phosphoramidothionates and thiolates [16] have larvicidal activity (LC 50 ) toward mosquito larvae in the ranges 0.62-10, 0.02-10 and 0.7-10 ppm, respectively.…”

Synthesis and anticholinesterasic activity of some .alpha.-thiosubstituted O-(methylcarbamoyl)oximes

“…The compounds described in this work belong to the group of the a-substituted O-(methylcarbamoy1)acetophenoximes studied by Fukuto et al (1969) and Jones et al (1972). Mrlina and Calmon (1980a,b) characterized the mechanism of hydrolysis for this group and discussed the anticholinesterasic activity versus physicochemical parameters.…”