Discovery of Novel CB2 Receptor Ligands by a Pharmacophore-Based Virtual Screening Workflow

来自 ACS

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作者：

P Markt，C Feldmann，JM Rollinger，S Raduner，D Schuster，J Kirchmair，S Distinto，GM Spitzer，G Wolber，C Laggner

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摘要：

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.

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关键词：

antibiotics antituberculosis biosynthesis capreomycin metabolic engineering viomycin

DOI：

10.1021/jm801044g

被引量：

年份：

2009