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Design, synthesis and biological evaluation of N-hydroxy-aminobenzyloxyarylamide analogues as novel selective κ opioid receptor antagonists.

Abstract：

:Aminobenzyloxyarylamide derivatives 1a-i and 2a-t were designed and synthesized as novel selective κ opioid receptor (KOR) antagonists. The benzoyl amide moiety of LY2456302 was changed into N-hydroxybenzamide and benzisoxazole-3(2H)-one to investigate whether it could increase the binding affinity or selectivity for KOR. All target compounds were evaluated in radioligand binding assays for opioid receptor binding affinity. These efforts led to the identification of compound 1c (κ Ki = 179.9 nM), which exhibited high affinity for KOR. Moreover, the selectivity of KOR over MOR and DOR increased nearly 2-fold and 7-fold, respectively, compared with (±)LY2456302.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

He G,Song Q,Wang J,Xu A,Peng K,Zhu Q,Xu Y

doi

10.1016/j.bmcl.2020.127236

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

127236

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(20)30341-3

journal_volume

30

pub_type

杂志文章

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