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Design and synthesis of novel δ opioid receptor agonists with an azatricyclodecane skeleton for improving blood-brain barrier penetration.

Abstract：

:We designed and synthesized novel δ opioid receptor (DOR) agonists 3a-i with an azatricyclodecane skeleton, which was a novel structural class of DOR agonists. Among them, 3b exhibited high values of binding affinity and potent agonistic activity for the DOR that were approximately equivalent to those of 2 which bore an oxazatricyclodecane skeleton. In vitro assays using the blood-brain barrier (BBB) permeability test kit supported the idea that 3b achieved an excellent BBB permeability by converting an oxygen atom of 2 to a carbon atom (methylene group) in the core skeleton. As a result, 3b showed potent antinociceptive effects.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Watanabe Y,Hayashida K,Saito D,Takahashi T,Sakai J,Nakata E,Kanda T,Iwai T,Hirayama S,Fujii H,Yamakawa T,Nagase H

doi

10.1016/j.bmcl.2017.05.072

subject

Has Abstract

pub_date

2017-08-01 00:00:00

pages

3495-3498

issue

15

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(17)30571-1

journal_volume

27

pub_type

杂志文章

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