Highly potent and selective cannabinoid receptor 2 agonists: Initial hit optimization of an adamantyl hit series identified from high-through-put screening

• Published in: Bioorganic & medicinal chemistry letters Vol. 23; no. 5; pp. 1177 - 1181
• Main Authors: Nettekoven, Matthias, Fingerle, Jürgen, Grether, Uwe, Grüner, Sabine, Kimbara, Atsushi, Püllmann, Bernd, Rogers-Evans, Mark, Röver, Stephan, Schuler, Franz, Schulz-Gasch, Tanja, Ullmer, Christoph
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.03.2013; Elsevier
• Subjects: Adamantane; Adamantane - analogs & derivatives; Adamantane - pharmacology; agonists; Cannabinoid receptor; Cannabinoid Receptor Agonists - chemistry; Cannabinoid Receptor Agonists - pharmacology; cannabinoids; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Drug Evaluation, Preclinical - methods; High-Throughput Screening Assays - methods; Hit optimization; Humans; Life Sciences & Biomedicine; Models, Molecular; Pharmacology & Pharmacy; Physical Sciences; physicochemical properties; Receptor, Cannabinoid, CB2 - agonists; Science & Technology; screening; Structure-Activity Relationship; β-Arrestin; β-Arrestin; Adamantane; Cannabinoid receptor; Hit optimization; TARGET; DRUG DISCOVERY; ENDOCANNABINOID SYSTEM; CB2 RECEPTORS; DISEASES; LIGANDS; ABSORPTION; beta-Arrestin; MODULATION; PERMEATION; INDEXES
• ISSN: 0960-894X; 1464-3405; 1464-3405
• DOI: 10.1016/j.bmcl.2013.01.044

A series of highly potent & selective adamantane derived CB2 agonists was identified in a high-throughput screen. A SAR was established and physicochemical properties were significantly improved. This was accompanied by potency of the compounds on the Q63R variant and varying β-arrestin data which will support the insight into their relevance for the in vivo situation.