Synthesis and Determination of the pKa Values of a Series of Bis(anilino)furazano[3,4-b]pyrazines

Mitochondrial uncouplers such as bis(anilino)furazano[3,4-b]pyrazines are potentially useful as metabolic probes and as pharmaceutical treatments for obesity. The ongoing development of such molecules would be facilitated by an ability to predict and control the pK(a) value of the dissociable proton(s). In this work, new analogues based on the aforementioned scaffold were prepared utilising a novel method for incorporating the aniline substituents. The pK(a) values of these species were measured using a bracketing indicator method. The pK(a) values correlated well with, and showed a strong dependence on, the electronic nature of the substituent (including for those at the ortho position). The second deprotonation of these species was also evaluated, with a similar trend noted.