Opioid agonists and antagonists. Peptides containing N-terminal allyl groups and/or a thiomethylene linkage in place of a peptide bond

Peptides containing N-allyl or N, N-diallyl groups at the N-terminus have been synthesized as potential opioid antagonists. A number of analogues with an amide bond replaced by a thiomethylene group have also been prepared. In brain binding assays and in guinea-pig ileum and mouse vas deferens preparations, the analogues generally displayed low affinity for μ- and δ-receptors as well as agonist activities in in vitro tests. N,N-Diallyl-Phe-D-Ala-Phe-Gly- NH2 (28) was found to be a moderately potent but highly selective antagonist at δ opiate receptors.