γ-Carbolines: A novel class of cannabinoid agonists with high aqueous solubility and restricted CNS penetration
| Autor: | Xuehong Luo, Xiao Hong Yu, Pourashraf Mehrnaz, Sanjay Srivastava, Dominic Salois, Cheng Yun-Xing, Kemal Payza, Christopher Walpole, Etienne Lessard, Stephane St-Onge, Tomaszewski Miroslaw |
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| Rok vydání: | 2012 |
| Předmět: |
Cannabinoid receptor
medicine.medical_treatment Clinical Biochemistry Analgesic Pain Pharmaceutical Science Pharmacology Biochemistry Cell Line Drug Stability Drug Discovery Aqueous solubility medicine Animals Humans Solubility Molecular Biology Analgesics Molecular Structure Cannabinoids Chemistry Organic Chemistry Chronic pain Brain medicine.disease Rats Cannabinoid Agonists Tolerability Molecular Medicine lipids (amino acids peptides and proteins) Cannabinoid Carbolines |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 22:1619-1624 |
| ISSN: | 0960-894X |
| Popis: | An oral, peripherally restricted CB1/CB2 agonist could provide an interesting approach to treat chronic pain by harnessing the analgesic properties of cannabinoids but without the well-known central side effects. γ-Carbolines are a novel class of potent mixed CB1/CB2 agonists characterized by attractive physicochemical properties including high aqueous solubility. Optimization of the series has led to the discovery of 29, which has oral activity in a rat inflammatory pain model and limited brain exposure at analgesic doses, consistent with a lower risk of CNS-mediated tolerability issues. |
| Databáze: | OpenAIRE |
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