Aromatic amines, structure-activity relationships

Benigni, R., Giuliani, A., Franke, R., and Gruska, A., Quantitative structure-activity relationships of mutagenic and carcinogenic aromatic amines, Chem. Rev., 100, 3697-3714, 2000. 

Benigni, R. and Passerini, L., Carcinogenicity of the aromatic amines from structure-activity relationships to mechanisms of action and risk assessment, Mutation Res. Rev., 511, 191-206, 2002. 

G. Kalopissis, Mutat. Res., 246, 45 (1991). Structure-Activity Relationships of Aromatic Amines in the Ames Salmonella typhimurium Assay. 

Each local anesthetic molecule has three general areas a lipophilic portion containing an aromatic ring, an intermediate chain and a hydrophilic amine functionality. The structure-activity relationships for local anesthetics can be described in terms of structural modifications to each of these three areas. Depending on the structure of the intermediate chain, local anesthetics are classified as either esters or amides. 

Franke R, Gruska A, Giuliani A, Benigni R. Prediction of rodent carcinogenicity of aromatic amines A quantitative structure-activity relationships model. Carcinogenesis 2001 22 1561-71. 

Sabbioni G. Hemoglobin binding of aromatic amines molecular dosimetry and quantitative structure-activity relationships for jV-oxidation. Environ Health Per-spect 1993 99 213-6. 

The aromatic amines phenothiazine, phenoxa-cine, and iminostUbene (formula [276]) proved to be about two orders of magnitude more effective than common phenolic antioxidants in their protective activity against oxidative nerve cell death (Moosmann et al. 2001). This remarkable efficacy could be directly correlated to calculated properties of the compound by means of a novel, quantitative structure-activity relationship model. 

Predictive Capability, Several empirical structure-activity relationships for oxidation by RO2 (polyani relation), HO (Hammett sigma-rho relations), and 02 have been developed. A large data base is available to estimate reliably the rate constants for new chemicals within a factor of 3-5. Precise evaluation of rate constants for highly susceptible compounds such as phenols, aromatic amines, alkyl sulfides, and electron-rich olefins and dienes is needed. Oxidation of saturated alkyl compounds including alkanes, haloalkanes, esters, and ketones is slow in water and air. Most chemicals excepting the above-mentioned compounds are readily oxidized by HO radicals. 

Hatch FT, Colvin ME. Quantitative structure-activity (QSAR) relationships of mutagenic aromatic and heterocyclic amines. Mutat Res 1997 376 87-96. 

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