Literature

Abstract

A focused screening strategy identified thienopyrimidine 1 as a hCB2 cannabinoid receptor agonist with moderate selectivity over the hCB1 receptor. This initial hit suffered from poor in vitro metabolic stability and high in vivo clearance. Structure-activity relationships describe the optimization and modification to a less lipophilic purine core. Examples from this novel series were found to be highly potent and fully efficacious agonists of the human CB2 receptor with excellent selectivity against CB1. Compound 10 possesses good biopharmaceutical properties, is highly water soluble and demonstrates robust oral activity in rodent models of joint pain.

DOI： 10.1016/j.bmcl.2012.06.035

Discovery and optimization of novel purines as potent and selective CB2 agonists

Bioorganic & Medicinal Chemistry Letters 2012.0

Selective Cannabinoid Receptor Type 2 (CB2) Agonists: Optimization of a Series of Purines Leading to the Identification of a Clinical Candidate for the Treatment of Osteoarthritic Pain

Journal of Medicinal Chemistry 2013.0

2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 1: Discovery of CB2 receptor selective compounds

Bioorganic & Medicinal Chemistry Letters 2007.0

2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 2: Orally bioavailable compounds

Bioorganic & Medicinal Chemistry Letters 2007.0

Discovery and Optimization of a Novel Series ofN-Arylamide Oxadiazoles as Potent, Highly Selective and Orally Bioavailable Cannabinoid Receptor 2 (CB<sub>2</sub>) Agonists

Journal of Medicinal Chemistry 2008.0

Novel pyridine derivatives as potent and selective CB2 cannabinoid receptor agonists