Opioid mimetics

Substitution of a dipeptide unit by a cychc dipeptide derivative within a peptide chain can induce certain conformational restraints that may alter the biological response via changing receptor selectivity. A facile procedure for synthesis of pyrazinone ring-containing opioid mimetics [21] has been elaborated, based on the cycHzation of readily available dipep-tidyl chloromethyl ketones [22] (Scheme 6). This method affords 2(IH)-pyrazinone derivatives containing substituents with desired functional groups at positions 3 and 6 in high yield. 

Schemes Synthesis of pyrazinone ring-containing opioid mimetics...

Opioid mimetics 272 Oxadiazoles, PEG-bound Bimgess reagent 139... 

Salvadori S, Attila M, Balboni G, Bianchi C, Bryant SD, Crescenzi O, Guerrini R, Picone D, Tancredi T, Temussi PA, Lazarus LH. 6 Opioid-mimetic antagonists prototypes for designing a new generation of ultraselective opioid peptides. Mol Med 1995 1 678-689. 

Application of the concept of conformational restriction to opioid peptides has produced fruitful results, insofar as peptide analogues and mimetics with interesting opioid activity profiles and high stability against enzymatic... 

The opioid alkaloids are classic examples of non-peptide ligands that have later been discovered to be mimetics of endogenous peptides. For example, morphine 5 (Figure 1.4.3) imitates the effect of flexible peptides, for example Met-enkephalin 4, at the common recognition site of the receptor for both compounds... 

Table 2.17 Nonpeptide Mimetics for Delta Opioid Receptors Based on Delta Opioid Peptides...

Table 29.2 Nonselective opioid receptor binding assay of enkephalin and endomorphin ji-turn mimetics...

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