1,2,4-OXADIAZOLE DERIVATIVES OF PHENYLALANINE - POTENTIAL INHIBITORS OF SUBSTANCE-P ENDOPEPTIDASE

The synthesis and the biological activity of a series of benzyl or aryl substituted 1,2,4-oxadiazole derivatives of phenyl-alanine are described. A base-promoted intermolecular cyclization reaction was performed using racemic tert-butyloxycarbonyl-protected phenylalanine methyl ester and an amidoxime. After deprotection of the amino function the compounds were evaluated for their affinity to rat brain NK1-receptors and as inhibitors of a specific substance P cleaving enzyme, substance P endopeptidase (SPE), isolated from human cerebrospinal fluid. The results indicate that several compounds are weak inhibitors of SPE. However, all compounds lacked appreciable NK1-receptor affinity.