1,2,4-Oxadiazole derivatives of phenylalanine: potential inhibitors of substance P endopeptidase

Article abstract of DOI:10.1016/0223-5234(93)90115-U

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.Keywords: 1,2,4-oxadiazoles / substance P endopeptidase / Phe-Phe mimetics / amide bioisostere / NK₁-receptor affinity