Synthesis of enkephalin analogs. Part VI. N,N-disubstituted derivatives.

Abstract

Synthesis of four new N,N-disubstituted derivatives of enkephalin analogs: All2Tyr-DMet-Gly-Phe-epsilon Ahx-OMe 5, Bu2Tyr-DMet-Gly-Phe-epsilon Ahx-OMe 6, All2Tyr-DMet-Gly-Phe-epsilon Ahx-epsilon Ahx-OMe 11 and Bu2Tyr-DMet-Gly-Phe-epsilon Ahx-epsilon Ahx-OMe 12 is reported. they were tested for agonistic and antagonistic activity. Compound 5 is a little more potent agonist (IC50 = 1.9 x 10(-7) M/l, GPI) than compound 6(IC50 = 7.2 x 10(-7) M/l, GPI). They both are highly selective to mu receptor, because they show no trace of activity to delta receptor in concentration up to 10(-5) M/l. Compound 11 and 12 are less active and not selective as agonists. None of these compounds showed antagonistic activity.