An in Silico Method for Predicting Ames Activities of Primary Aromatic Amines by Calculating the Stabilities of Nitrenium Ions was written by Bentzien, Joerg;Hickey, Eugene R.;Kemper, Raymond A.;Brewer, Mark L.;Dyekjaer, Jane D.;East, Stephen P.;Whittaker, Mark. And the article was included in Journal of Chemical Information and Modeling in 2010.Synthetic Route of C7H6N2S This article mentions the following:
In this paper, the authors describe an in silico first principal approach to predict the mutagenic potential of primary aromatic amines. This approach is based on the so-called “nitrenium hypothesis”, which was developed by Ford et al. in the early 1990s. This hypothesis asserts that the mutagenic effect for this class of mols. is mediated through the transient formation of a nitrenium ion and that the stability of this cation is correlated with the mutagenic potential. Here the authors use quantum mech. calculations at different levels of theory (semiempirical AM1, ab initio HF/3-21G, HF/6-311G(d,p), and DFT/B3LYP/6-311G(d,p)) to compute the stability of nitrenium ions. When applied to a test set of 257 primary aromatic amines, the authors show that this method can correctly differentiate between Ames active and inactive compounds, and furthermore that it is able to rationalize and predict SAR trends within structurally related chem. series. For this test set, the AM1 nitrenium stability calculations are found to provide a good balance between speed and accuracy, resulting in an overall accuracy of 85%, and sensitivity and specificity of 91% and 72%, resp. The nitrenium-based predictions are also compared to the com. software packages DEREK, MULTICASE, and the MOE-Toxicophore descriptor. One advantage of the approach presented here is that the calculation of relative stabilities results in a continuous spectrum of activities and not a simple yes/no answer. This allows the authors to observe and rationalize subtle trends due to the different electrostatic properties of the organic mols. The authors’ results strongly indicate that nitrenium ion stability calculations should be used as a complementary approach to assist the medicinal chemist in prioritizing and selecting nonmutagenic primary aromatic amines during preclin. drug discovery programs. In the experiment, the researchers used many compounds, for example, Benzo[d]isothiazol-5-amine (cas: 53473-85-1Synthetic Route of C7H6N2S).
Benzo[d]isothiazol-5-amine (cas: 53473-85-1) belongs to isothiazole derivatives. Isothiazole is more toxic than pyridine. But the more substituted isothiazoles are usually far less toxic. Various penicillins and cephalosporins having an isothiazole ring system have shown considerable antibacterial efficacy against Gram-positive and Gram-negative bacteria.Synthetic Route of C7H6N2S
Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com