Methylanilines, demethylation

Galliani G, Nali M, Rindone B, et al. The rate of N-demethylation of N, N-dimethylanilines and N-methylanilines by rat-liver microsomes is related to their first ionization potential, their lipophilicity and to a steric bulk factor. Xenobiotica 1986 16(6) 511—517. 

Animals. Degrades to iV-methylaniline which is subsequently demethylated, acetylated and hydroxylated to 4-aminophenol and its sulfate and glucuronide conjugates... 

Evidence in favor of the electron-transfer mechanism has also come from studies on substrates such as Ai-ethyl-7V-methylaniline which show a demethylation/... 

Oxidative demethylation of A -alkyl-JV-methylanilines with nitrone [258] proceeds via intermediates having a N-O-N subunit. A [2.3]sigmatropic rearrangement leads to the decomposition. 

With regard to reproduction, demethylchlordimeform was more active than chlordimeform in decreasing fecundity and egg hatch in spider mites 4-chloro-2-methylaniline also possessed some activity against egg hatch only, while the formanilide was inactive ( 9). Thus it seemed that with chlordimeform the demethyl metabolite played a major role in its effects on spider mite reproduction. However, the results with amitraz and U-44193 were more difficult to interpret. Their common metabolites, BTS-27271, 2,4-dimethylformanilide, and 2,4-dimethylaniline all significantly decreased fecundity and egg hatch, yet U-44193 was one of the most active inhibitors of these processes in mites, and amitraz had no significant effect. Examination of metabolism data (28) revealed that in twospotted spider mites exposed to U-44193 or amitraz, levels of parent compounds were low (<1.0%), but levels of BTS-27271 were several fold higher in mites exposed to... 

Photo-induced demethylation of 4-nitro-iV,A-dimethylaniline,to give 4-nitro-N-methylaniline, has been observed upon excitation in the presence of an external acceptor in benzene or the methoxide ion in methanol. A quantum chemical study of the photodissociation of the alkyl C-N bond in AT-substituted anilines, PhNH-R (R = Me, PhCH2, Ph2CH, Ph3C), has also been carried out. " ... 

Horseradish peroxidase (HRP), which demethylates A, A -dialkylanilines in the presence of H2O2 and O2 [133], oxidizes iV -cyclopropyl, A -methylaniline to A -methylaniline and a product that arises via radical ring opening of the cyclopropyl group (Fig. 4.19). In contrast, the... 

Reactions.—Cleavage of prenyl and allyl ethers has been discussed earlier in this Report. Some aliphatic ethers can be cleaved by thallium(iii) nitrate in acetic anhydride.New reagents for the demethylation of aryl methyl ethers include the stable, crystalline, and easily handled complexes of boron halides BBr3 and BCI3 with dimethyl sulphide,and the salt obtained from treatment of N-methylaniline with sodium hydride in HMPA. The latter system cleaves methyl aryl ethers more readily than benzyl aryl ethers. 

There may be species differences in the induction of drug metabolism in extra-hepatic tissues. For example, treatment of rabbits with phenobarbital significantly increases the hydroxylation and N-demethylation of N-methylaniline and the microsomal protein and cytochrome P-4S0 content of liver and kidney microsomes, but not in lung and small intestine. However, treatment of rats with phenobarbital, 3,4-benzpyrene, or DDT does not significantly affect the levels of cytochrome P-4S0 or drug metabolism in kidney microsomes. 

SKF 525-A inhibits the in vitro metabolism of several barbiturates, meperidine, aminopyrine, and codeine, the formation of morphine glucuronide, and the hydrolysis of procaine and ethylglycinexylidide. However, SKF 525-A has no significant effect on the microsomal N-demethylation of monomethyl-4-aminoantipyrine, N-methylaniline or 3-methyl-4-monomethylaminoazobenzene, the O-dealkylation of phenacetin, the hydroxylation of acetanilide, or the sulphoxidation of chlorpro-mazine. 

---