A diketopiperazine (DKP), also known as a dioxopiperazine or piperazinedione, is a class of organic molecules in which the two nitrogen atoms of a piperazine 6-membered ring are part of amide linkages. There are three regioisomers possible, differing in the locations of the two carbonyl groups around the ring. While these isomers share a piperazine core, optimal strategies for their synthesis differ. The 2,3-diketopiperazines may be viewed as oxamides obtained from ethylenediamine. 2,5-Diketopiperazines are cyclodipeptides often obtainable via condensation of two α-amino acids. 2,6-Diketopiperazines may be viewed as cyclized imide derivatives derived from iminodiacetic acids. Of these three isomeric diketopiperazines, the 2,5-derivatives have attracted the greatest interest.
As a result of the structural similarities of DKPs to peptides,. their appearance in biologically active natural products has inspired medicinal chemists to use DKPs to circumvent the poor physical and metabolic properties of peptides in the course of drug discovery.
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