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Investigation of Beckett–Casy model 1: Synthesis of novel 16,17-seco-naltrexone derivatives and their pharmacology
- Source :
- Bioorganic & Medicinal Chemistry Letters. 20:1055-1058
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- We synthesized novel 15-16 nornaltrexone derivatives 9, 11 and 22 to examine the importance of the cavity in the Beckett-Casy model, which was proposed to interact with the 15-16 ethylene moiety in the morphine structure. All the synthesized compounds showed lower affinities for the opioid receptor than did the naltrexone (10). The binding affinities of 14-OH derivatives 11, in which the rotation of the 9-17 bond would be restricted by an intramolecular hydrogen bond, was improved compared to the corresponding 14-H derivatives 9. Compound 22 whose 9-17 bond was strictly fixed by the ethylene bridge hardly bound to the opioid receptor. Compound 26 also showed very weak binding affinity in spite of the existence of the 15-16 ethylene unit. We proposed an important role for the orientation of the lone electron pair on the 17-nitrogen rather than the significance of the cavity in the Beckett-Casy model.
- Subjects :
- Models, Molecular
Ethylene
Stereochemistry
Chemistry
Hydrogen bond
medicine.drug_class
Chemistry, Pharmaceutical
Organic Chemistry
Clinical Biochemistry
Pharmaceutical Science
Biochemistry
Affinities
Chemical synthesis
Naltrexone
Structure-Activity Relationship
chemistry.chemical_compound
Opioid receptor
Intramolecular force
Drug Discovery
medicine
Molecular Medicine
Moiety
Molecular Biology
medicine.drug
Subjects
Details
- ISSN :
- 0960894X
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Accession number :
- edsair.doi.dedup.....2d4e23347f4bcc6236ba9e26d9e3d28b