Aryl 1,4-diazepane compounds as potent and selective CB2 agonists: optimization of drug-like properties and target independent parameters.

A high throughput screening campaign identified aryl 1,4-diazepane compounds as potent and selective cannabinoid receptor 2 agonists as compared to cannabinoid receptor 1. This class of compounds suffered from poor drug-like parameters as well as low microsomal stability and poor solubility. Structure-activity relationships are described with a focus on improving the drug-like parameters resulting in compounds with improved solubility and permeability.

1,4-Diazepane compounds as potent and selective CB2 agonists: optimization of metabolic stability.

A high-throughput screening campaign has identified 1,4-diazepane compounds which are potent Cannabinoid receptor 2 agonists with excellent selectivity against the Cannabinoid receptor 1. This class of compounds suffered from low metabolic stability. Following various strategies, compounds with a good stability in liver microsomes and rat PK profile have been identified.

Morpholine containing CB2 selective agonists.

Identification and optimization of two classes of CB2 selective agonists are described. A representative from each class is profiled in a murine model of inflammation and each shows similar efficacy to prednisolone upon oral dosing.

Arylsulfonamide CB2 receptor agonists: SAR and optimization of CB2 selectivity.

A high-throughput screening campaign resulted in the discovery of a highly potent dual cannabinoid receptor 1 (CB1) and 2 (CB2) agonist. Following a thorough SAR exploration, a series of selective CB2 full agonists were identified.