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Synthesis and evaluation of novel opioid ligands with a C-homomorphinan skeleton
- Source :
- Bioorganicmedicinal chemistry. 24(10)
- Publication Year :
- 2016
-
Abstract
- As the reports about C-homomorphinans with the seven-membered C-ring are much fewer than those of morphinan derivatives with a six-membered C-ring, we attempted to synthesize C-homomorphinan derivatives and to evaluate their opioid activities. C-Homomorphinan 5 showed sufficient binding affinities to the opioid receptors. C-Homomorphinan derivatives possessing the δ address moiety such as indole (NTI-type), quinoline, or benzylidene (BNTX-type) functionalities showed the strongest binding affinities for the δ receptor among the three types of opioid receptors, which indicated that the C-homomorphinan skeleton sufficiently functions as a message-part in the ligand. Although NTI-type compound 8 and quinoline compound 9 with C-homomorphinan scaffold exhibited lower affinities and selectivities for the δ receptor than the corresponding morphinan derivatives did, both the binding affinity and selectivity for the δ receptor of BNTX-type compound 12 with a seven-membered C-ring were improved compared with the corresponding compounds with a six-membered C-ring including BNTX itself. BNTX-Type compound 12 was the most selective δ receptor antagonist among the tested compounds.
- Subjects :
- Models, Molecular
Stereochemistry
Narcotic Antagonists
Clinical Biochemistry
Pharmaceutical Science
CHO Cells
010402 general chemistry
Ligands
01 natural sciences
Biochemistry
Benzylidene Compounds
chemistry.chemical_compound
Structure-Activity Relationship
Cricetulus
Receptors, Opioid, delta
Drug Discovery
Structure–activity relationship
Moiety
Animals
Humans
Receptor
Molecular Biology
Indole test
010405 organic chemistry
Organic Chemistry
Quinoline
Ligand (biochemistry)
Affinities
Naltrexone
0104 chemical sciences
Analgesics, Opioid
chemistry
Morphinans
Benzylidene compounds
Receptors, Opioid
Quinolines
Molecular Medicine
Subjects
Details
- ISSN :
- 14643391
- Volume :
- 24
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry
- Accession number :
- edsair.doi.dedup.....c84caade615f85effeec5f106ed92c1c