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

Matthias Nettekoven; Jürgen Fingerle; Uwe Grether; Sabine Grüner; Atsushi Kimbara; Bernd Püllmann; Mark Rogers-Evans; Stephan Röver; Franz Schuler; Tanja Schulz-Gasch; Christoph Ullmer

doi:10.1016/j.bmcl.2013.01.044

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

Bioorg Med Chem Lett. 2013 Mar 1;23(5):1177-81. doi: 10.1016/j.bmcl.2013.01.044. Epub 2013 Jan 23.

Authors

Matthias Nettekoven¹, Jürgen Fingerle, Uwe Grether, Sabine Grüner, Atsushi Kimbara, Bernd Püllmann, Mark Rogers-Evans, Stephan Röver, Franz Schuler, Tanja Schulz-Gasch, Christoph Ullmer

Affiliation

¹ F. Hoffmann-La Roche Ltd, Pharma Research & Early Development, Medicinal Chemistry, Grenzacher Str. 124, 4070 Basel, Switzerland. matthias.nettekoven@roche.com

PMID: 23380378
DOI: 10.1016/j.bmcl.2013.01.044

Abstract

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.

MeSH terms

Adamantane / analogs & derivatives*
Adamantane / pharmacology
Cannabinoid Receptor Agonists / chemistry*
Cannabinoid Receptor Agonists / pharmacology*
Drug Evaluation, Preclinical / methods
High-Throughput Screening Assays / methods
Humans
Models, Molecular
Receptor, Cannabinoid, CB2 / agonists*
Structure-Activity Relationship

Substances

Cannabinoid Receptor Agonists
Receptor, Cannabinoid, CB2
Adamantane