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Bioorg Med Chem Lett. 2006 Nov 15;16(22):5793-6. Epub 2006 Sep 1.

Synthesis of 3,6-bis[H-Tyr/H-Dmt-NH(CH2)m,n]-2(1H)pyrazinone derivatives: function of alkyl chain length on opioid activity.

Author information

1
The Graduate School of Food and Medicinal Sciences, Kobe Gakuin University, Kobe 651-2180, Japan.

Abstract

Dimeric opioid analogues linked to a pyrazinone platform, 3-[Tyr/Dmt-NH(CH2)m]-6-[Tyr/Dmt-NH(CH2)n]-2(1H)-pyrazinone (m, n=3 or 4), were synthesized. The Tyr-containing compound (m=4, n=3) exhibited mu-receptor affinity (K(i)mu; 7.58 nM) comparable to that of morphine, while the Dmt derivatives exhibited considerably higher affinity (K(i)mu; 0.021-0.051 nM) with corresponding agonism (IC50=1.79-4.93 nM). Interestingly one compound (m=4, n=3) revealed modest delta-opioid agonism; the converse analogue (m=3, n=4), however, was inactive in MVD assay.

PMID:
16949282
PMCID:
PMC2636969
DOI:
10.1016/j.bmcl.2006.08.079
[Indexed for MEDLINE]
Free PMC Article

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