当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Essential structure of orexin 1 receptor antagonist YNT-707, Part IV: The role of D-ring in 4,5-epoxymorphinan on the orexin 1 receptor antagonistic activity.

Essential structure of orexin 1 receptor antagonist YNT-707, Part IV: The role of D-ring in 4,5-epoxymorphinan on the orexin 1 receptor antagonistic activity.

Abstract：

:The orexin 1 receptor (OX1R) antagonists carrying a morphinan skeleton such as YNT-707 (2) and YNT-1310 (3) showed potent and extremely high selective antagonistic activity against OX1R. In the course of our study of the essential structure of YNT-707 for high binding affinity against OX1R, we prepared derivatives of 2 without the D- and 4,5-epoxy rings to clarify the roles of these structural determinants toward OX1R antagonistic activity. The D- and 4,5-epoxy rings played important roles for the active orientation of the 17-sulfonamide and 6-amide side chains. Finally, we identified the simple structure required for selective OX1R antagonistic activity in the complex morphinan skeleton, which is expected to be a useful scaffold for further design of OX1R ligands.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Saitoh T,Seki K,Nakajima R,Yamamoto N,Kutsumura N,Nagumo Y,Irukayama-Tomobe Y,Ogawa Y,Ishikawa Y,Tanimura R,Yanagisawa M,Nagase H

doi

10.1016/j.bmcl.2019.07.039

subject

Has Abstract

pub_date

2019-09-15 00:00:00

pages

2655-2658

issue

18

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(19)30495-0

journal_volume

29

pub_type

杂志文章

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