C-Homomorphinan Derivatives as Lead Compounds to Obtain Safer and More Clinically Useful Analgesics

C-Homomorphinan Derivatives as Lead Compounds to Obtain Safer and More Clinically Useful Analgesics

Buprenorphine shows strong analgesic effects on moderate to severe pain. Although buprenorphine can be used more safely than other opioid analgesics, it has room for improvement in clinical utility. Investigation of compounds structurally related to buprenorphine should be an approach to obtain nove...

Full description

Saved in:
Bibliographic Details
Published in:Chemical & pharmaceutical bulletin Vol. 65; no. 10; pp. 920 - 929
Main Authors: Ishikawa, Kyoko, Karaki, Fumika, Tayama, Kaoru, Higashi, Eika, Hirayama, Shigeto, Itoh, Kennosuke, Fujii, Hideaki
Format: Journal Article
Language:English
Published: Japan The Pharmaceutical Society of Japan 2017
Pharmaceutical Society of Japan
Japan Science and Technology Agency
Subjects:
Analgesics
Analgesics, Opioid - chemical synthesis
Analgesics, Opioid - chemistry
Animals
Buprenorphine
Buprenorphine - analogs & derivatives
Buprenorphine - chemistry
C-homomorphinan
CHO Cells
Cricetinae
Cricetulus
Cyclization
Derivatives
Humans
Kinetics
Lead compounds
Molecular Conformation
Morphinans - chemical synthesis
Morphinans - chemistry
Narcotics
opioid
Opioid receptors
Pain
Pain perception
Pharmacology
Protein Binding
Receptor mechanisms
Receptors
Receptors, Opioid - chemistry
Receptors, Opioid - genetics
Receptors, Opioid - metabolism
Recombinant Proteins - biosynthesis
Recombinant Proteins - chemistry
Recombinant Proteins - isolation & purification
buprenorphine
opioid
C-homomorphinan
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Buprenorphine shows strong analgesic effects on moderate to severe pain. Although buprenorphine can be used more safely than other opioid analgesics, it has room for improvement in clinical utility. Investigation of compounds structurally related to buprenorphine should be an approach to obtain novel analgesics with safer and improved profiles compared to buprenorphine. In the course of our previous studies, we observed that derivatives obtained by cyclizing C-homomorphinans were structurally related to buprenorphine. Hence, we synthesized cyclized C-homomorphinan derivatives with various oxygen functionalities on the side chains and evaluated their in vitro pharmacological profiles for the opioid receptors. Among the tested compounds, methyl ketone 2a with an N-methyl group showed full agonistic activities for the μ and the δ receptors and partial agonistic activity for the κ receptor. These properties were similar to those of norbuprenorphine, a major metabolite of buprenorphine, which reportedly contributes to the antinociceptive effect of buprenorphine. From these results, we concluded that cyclized C-homomorphinan would be a possible lead compound to obtain novel analgesics with buprenorphine-like properties.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0009-2363
1347-5223
DOI:10.1248/cpb.c17-00385