INHIBITION OF THE HILL REACTION BY METHYLTHIO-4,6-BIS(MONOALKYLAMINO)-1,3,5-TRIAZINES - A QSAR STUDY

The inhibitory activity in the Hill reaction for a series of 29 methyl thio-3,6-bis(monoalkylamino)-1,3,5-triazines has been modeled using mo lecular connectivity indices as structural descriptors. From the gener ated QSAR model it can be inferred that the inhibitory potency of the triazine derivatives is predominantly controlled by the size of alkyla mino substituents. The additional structural feature that favorably af fects the activity is the degree of branching on the a-carbon atom of the larger alkylamino moiety. The obtained model resembles that for lu oromethylthio-4,6-bis(monoalkylamino)-triazines, which suggests that t he 2-methylthio and 2-difluoromethylthio derivatives are oriented in a similar way in the receptor cavity. By applying dominant component an alysis (the recently proposed method for removing the redundant inform ation 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. (C) 1997 Elsevier Science B.V.