Figure 1. Positional isomerization of pyridines through nitrogen relocation (IMAGE)
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a. Pyridine is the most common heterocycle found in drug molecules. Abiraterone, a pyridine-containing drug, illustrates how biological activity changes markedly depending on where a substituent sits on the ring. The reference point that defines this position is the nitrogen atom within the ring.
b. Two routes lead to a positional isomer. The upper route represents the conventional approach, in which the substituent itself is moved to a different position; the lower route is the strategy developed in this work, in which the substituent remains untouched, and the ring nitrogen is relocated instead. The two paths move different atoms yet converge on the same compound.
c. Nitrogen relocation applied to etoricoxib, an anti-inflammatory drug. An auxiliary nitrogen atom is first introduced at the pyridine nitrogen to form an intermediate; a new nitrogen is then inserted at the desired ring position while the original nitrogen is released as stable nitrogen gas (N2). The newly introduced nitrogen remains as a member of the ring, giving a positional isomer that differs only in the location of the nitrogen atom.
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