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Updated: May 25, 2026

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals
Published on: April 19, 2019
γ-Carbolines: a novel class of cannabinoid agonists with high aqueous solubility and restricted CNS penetration
Yun-Xing Cheng1, Mehrnaz Pourashraf, Xuehong Luo
1Department of Medicinal Chemistry, AstraZeneca R&D Montreal, Saint-Laurent, Quebec, Canada. mirek.tomaszewski@astrazeneca.com
Abstract:
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.
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