Discovery and synthesis of a new class of opioid ligand having a 3-azabicyclo[3.1.0]hexane core. An example of a ‘magic methyl’ giving a 35-fold improvement in binding
| Autor: | Yogesh A. Sabnis, Alan John Pettman, Bernard Joseph Banks, Neil Feeder, Robert Crook, Graham Lunn |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Stereochemistry
medicine.drug_class Clinical Biochemistry Drug Evaluation Preclinical Receptors Opioid mu Administration Oral Pharmaceutical Science CHO Cells Ligands Biochemistry chemistry.chemical_compound Cricetulus Dogs In vivo Opioid receptor Cricetinae Drug Discovery medicine Animals Hexanes Humans Molecular Biology Sulfonamides Chemistry Pruritus Organic Chemistry Antagonist Rats Hexane Opioid Molecular Medicine Azabicyclo Compounds Protein Binding medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 21:4608-4611 |
| ISSN: | 0960-894X |
| Popis: | In looking for a novel achiral μ opioid receptor antagonist for the treatment of pruritus, we designed and synthesised azabicyclo[3.1.0]hexane compounds as a new class of opioid ligand. During optimisation, an addition of a single methyl resulted in a 35-fold improvement in binding. An early example from the series had excellent μ opioid receptor antagonist antagonist activity and was very effective in an in vivo pruritus study. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect