185012-05-9Relevant articles and documents
Syntheses and properties of 1-methyl-3-phenylaminobenzimidazolium salts, models of DNA adducts of N7-arylaminodeoxyguanosinium salt
Kaiya,Fujiwara,Kohda
, p. 993 - 1001 (2007/10/03)
When arylaminating carcinogens are administered to cells, they mainly generate the C8-arylamino-2'-deoxyguanosine adduct in DNA. A mechanism for this was proposed in which N7-arylaminated 2'-deoxyguanosine acts as an intermediate; however, it remained unclear whether this is actually the case. To elucidate the mechanisms involved in the generation of this adduct, a series of 5-substituted 1-methylbenzimidazole derivatives were used as models of the imidazole moiety of 2'-deoxyguanosine. Syntheses of a series of 5-substituted (CH3, H, F, CF3, or NO2) 1-methyl-3-phenylaminobenzimidazolium salts (7) and their related compounds were carried out, and the chemical characteristics of these products were examined. Heating compound 7 at 80 °C for 48 h in H2O/MeOH provided 5-substituted 1-methyl-2-oxo-2,3-dihydrobenzimidazoles but only when this compound contained a CF3 or NO2 substituent. Compound 7 decomposed in alkaline media, and its rate of decomposition increased when this compound had a stronger electron-withdrawing substituent. The product obtained under these conditions was 4-substituted N1-methyl-2-phenylazoaniline. On the other hand, when 1-methyl-3-(4-nitrophenylamino)benzimidazolium salt was treated under the same conditions as described above, it generated a demethylated product, 1-(4-nitrophenylamino)benzimidazole, when heated in H2O/MeOH and N1-formyl-N1-methyl-2-phenylazoaniline when treated in alkaline media. When the chemical characteristics of 3-phenylamino and 3-amino groups were compared using 3-substituted 1-methyl-5-(trifluoromethyl)benzimidazoles, the 3-phenylamino derivative was found to be more reactive.
