Discovery of novel CB2 receptor ligands by a pharmacophore-based virtual screening workflow

Markt, Patrick; Feldmann, Clemens; Rollinger, Judith Maria; Raduner, Stefan; Schuster, Daniela; Kirchmair, Johannes; Distinto, Simona; Spitzer, Gudrun Maria; Wolber, Gerhard; Laggner, Christian; Altmann, Karl-Heinz; Langer, Thierry; Gertsch, Jürg (2009). Discovery of novel CB2 receptor ligands by a pharmacophore-based virtual screening workflow. Journal of medicinal chemistry, 52(2), pp. 369-78. Easton, Pa.: American Chemical Society 10.1021/jm801044g

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Cannabinoid receptor 2 (CB(2) receptor) ligands are potential candidates for the therapy of chronic pain, inflammatory disorders, atherosclerosis, and osteoporosis. We describe the development of pharmacophore models for CB(2) receptor ligands, as well as a pharmacophore-based virtual screening workflow, which resulted in 14 hits for experimental follow-up. Seven compounds were identified with K(i) values below 25 microM. The CB(2) receptor-selective pyridine tetrahydrocannabinol analogue 8 (K(i) = 1.78 microM) was identified as a CB(2) partial agonist. Acetamides 12 (K(i) = 1.35 microM) and 18 (K(i) = 2.1 microM) represent new scaffolds for CB(2) receptor-selective antagonists and inverse agonists, respectively. Overall, our pharmacophore-based workflow yielded three novel scaffolds for the chemical development of CB(2) receptor ligands.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Gertsch, Jürg

ISSN:

0022-2623

Publisher:

American Chemical Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:12

Last Modified:

04 May 2014 23:23

Publisher DOI:

10.1021/jm801044g

PubMed ID:

19143566

Web of Science ID:

000262522100016

URI:

https://boris.unibe.ch/id/eprint/31624 (FactScience: 196255)

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