Comparative Study of the Synthesis and Structural and Physicochemical Properties of Diketopiperazines vs Aza-diketopiperazines

Aza-diketopiperazines
(aza-DKPs) represent an underprivileged motif
obtained by scaffold hopping of 2,5-diketopiperazines (2,5-DKPs).
Herein, we compare the synthesis and the structural and physicochemical
properties of aza-DKP 4 vs 2,5-DKP 7. Thus,
X-ray and 1H NMR studies show that aza-DKP 4 is a rigid and nonflat scaffold like the 2,5-DKP 7.
Moreover, the replacement of one Cα-stereogenic center
by a nitrogen atom results in a significant improvement of both the
water solubility and the microsomal stability.