Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 27, Issue 17, Pages 4176-4179Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2017.07.011
Keywords
Orexin; Opioid; Nalfurafine; YNT-707; 4,5-Epoxy ring; Morphinan
Categories
Funding
- JSPS KAKENHI [15K16557, 16H05098]
- MEXT [JP15H05942]
- Toray Industries, Inc.
- World Premier International Research Center (WPI) Initiative, Japan
- Grants-in-Aid for Scientific Research [15H05942, 15H05935, 17H06095, 15K16557, 16H05098] Funding Source: KAKEN
Ask authors/readers for more resources
The essential structure of the orexin 1 receptor (OX1R) antagonist YNT-707 (2) was clarified, particularly the roles to OX1R antagonist activities of the 3-OMe, the 4,5-epoxy ring, the 14-hydroxy group, and the orientation of the 6-amide side chain. The 3-OMe and 17-sulfonamide group were shown to be essential for the OX1R antagonistic activity. The 4,5-epoxy ring plays an important role for the active orientation of the 6-amide group. The 14-hydroxy group could lower the activity of the 6 beta-amide isomer by the interaction of the 14-hydroxy group with the 6-amide group, which could orient the 6-amide group toward the upper side of the C-ring. Finally, we proposed the difference in the active conformation between OX1R and it opioid receptor (KOR), especially in the orientation of the 6-amide group which is expected to be a useful guide for medicinal chemists to design OX1R ligands. (C) 2017 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available