Inhibition of the Hill reaction by 2-methylthio-4,6-bis (monoalkylamino)-1,3,5-triazines A QSAR study

Abstract

The inhibitory activity in the Hill reaction for a series of 29 2-methylthio-4,6-bis(monoalkylamino)-1,3,5-triazines has been modeled using molecular connectivity indices as structural descriptors. From the generated QSAR model it can be inferred that the inhibitory potency of the triazine derivatives is predominantly controlled by the size of alkylamino substituents. The additional structural feature that favorably affects the activity is the degree of branching on the α-carbon atom of the larger alkylamino moiety. The obtained model resembles that for 2-difluoromethylthio-4,6-bis(monoalkylamino)-triazines, which suggests that the 2-methylthio and 2-difluoromethylthio derivatives are oriented in a similar way in the receptor cavity. By applying dominant component analysis (the recently proposed method for removing the redundant information from the correlated variables), it was found that the determined quantitative relationships between activity and the nonorthogonalized structural descriptors for 2-methylthio derivatives can be expressed in a simpler form.