Design and synthesis of novel delta opioid receptor agonists and their pharmacologies.

Abstract:

:We re-examined the accessory site of the 4,5-epoxymorphinan skeleton by camdas conformational analysis in an effort to deign novel delta opioid receptor antagonists. We synthesized three novel compounds (SN-11, 23 and 28) with a 10-methylene bridge and without a 4,5-epoxy ring. Among them, compounds SN-23 (17-isobutyl derivative) and SN-28 (17-methyl derivative) showed very strong agonist activity (over 10 times more than TAN-67). SN-28 also showed high delta selectivity. The delta agonist activity of SN-23 was weaker than that of SN-28, but in terms of the delta selectivity, SN-23 was higher than that of SN-28. These unexpected results indicated that the 4,5-epoxy ring, but not the 10-methylene bridge, was an accessory site in delta opioid receptor agonists.

journal_name

Bioorg Med Chem Lett

authors

Nagase H,Osa Y,Nemoto T,Fujii H,Imai M,Nakamura T,Kanemasa T,Kato A,Gouda H,Hirono S

doi

10.1016/j.bmcl.2009.03.099

subject

Has Abstract

pub_date

2009-05-15 00:00:00

pages

2792-5

issue

10

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)00412-0

journal_volume

19

pub_type

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