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 Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Nagase H,Osa Y,Nemoto T,Fujii H,Imai M,Nakamura T,Kanemasa T,Kato A,Gouda H,Hirono Sdoi
10.1016/j.bmcl.2009.03.099subject
Has Abstractpub_date
2009-05-15 00:00:00pages
2792-5issue
10eissn
0960-894Xissn
1464-3405pii
S0960-894X(09)00412-0journal_volume
19pub_type
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