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Enkephalin Analogs as Systemically Active Antinociceptive Agents: O- and N-Alkylated Derivatives of the Dipeptide Amide L-2,6-Dimethyltyrosyl-N-(3-phenylpropyl)-D-alaninamide
Journal article   Peer reviewed

Enkephalin Analogs as Systemically Active Antinociceptive Agents: O- and N-Alkylated Derivatives of the Dipeptide Amide L-2,6-Dimethyltyrosyl-N-(3-phenylpropyl)-D-alaninamide

Barnett S Pitzele, Robert W Hamilton, Kathleen D Kudla, Sofya Tsymbalov, Awilda Stapelfeld, Michael A Savage, Michael Clare, Donna L Hammond and Donald W Hansen
Journal of medicinal chemistry, Vol.37(7), pp.888-896
04/01/1994
DOI: 10.1021/jm00033a005
PMID: 7908696
url
https://doi.org/10.7270/q27h1hn2View
Open Access

Abstract

A number of O- and N-alkylated derivatives of the antinociceptive, orally active, μ-opioid-selective truncated enkephalin analog l-2,6-dimethyltyrosyl-N-(3-phenylpropyl)-d-alaninamide(2,SC-39566) were synthesized to explore the structure-activity relationships of the series. The parent molecule is quite forgiving of substitution on the tyrosyl phenolic moiety and on the alanyl nitrogen. The tyrosyl and (phenylpropyl)amide NH sites, however, appear to be critical to interactions with the receptor, for even modest changes at these sites cause great loss of binding potency.

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