Pyrazole derived from (+)-3-carene; a novel potent, selective scaffold for sphingosine-1-phosphate (S1P 1) receptor agonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 1; pp. 35 - 37
• Main Authors: Zécri, Frédéric J., Albert, Rainer, Landrum, Gregory, Hinterding, Klaus, Cooke, Nigel G., Guerini, Danilo, Streiff, Markus, Bruns, Christian, Nuesslein-Hildesheim, Barbara
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 2010; Elsevier
• Subjects: Biological and medical sciences; Carene; High-Throughput Screening Assays; Hydrogen Bonding; Immunomodulators; Medical sciences; Monoterpenes - chemistry; Pharmacology. Drug treatments; Pharmacophore model; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Receptors, Lysosphingolipid - agonists; Receptors, Lysosphingolipid - metabolism; S1P 1 agonist; Stereoisomerism; Structure-Activity Relationship; S1P 1 agonist; Carene; Pharmacophore model; edg1 lysophospholipid receptor; Agonist; Nitrogen heterocycle; Selectivity; Tricyclic compound; Modeling; S1P; Structure activity relation; Molecular model; Pyrazole derivatives; Affinity; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.11.045

High throughput screening and hit to lead optimization led to the identification of ‘carene’ as a promising scaffold showing selective S1P
1 receptor agonism. In parallel to this work we have established a pharmacophore model for the S1P
1 receptor highlighting the minimal structural requirement necessary for potent receptor agonism.