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

Frédéric J Zécri; Rainer Albert; Gregory Landrum; Klaus Hinterding; Nigel G Cooke; Danilo Guerini; Markus Streiff; Christian Bruns; Barbara Nuesslein-Hildesheim

doi:10.1016/j.bmcl.2009.11.045

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

Bioorg Med Chem Lett. 2010 Jan 1;20(1):35-7. doi: 10.1016/j.bmcl.2009.11.045. Epub 2009 Nov 15.

Authors

Frédéric J Zécri¹, Rainer Albert, Gregory Landrum, Klaus Hinterding, Nigel G Cooke, Danilo Guerini, Markus Streiff, Christian Bruns, Barbara Nuesslein-Hildesheim

Affiliation

¹ Novartis Institutes for BioMedical Research, Novartis Campus, CH-4056 Basel, Switzerland. frederic.zecri@novartis.com

PMID: 19954976
DOI: 10.1016/j.bmcl.2009.11.045

Abstract

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.

MeSH terms

Bicyclic Monoterpenes
High-Throughput Screening Assays
Hydrogen Bonding
Monoterpenes / chemistry*
Pyrazoles / chemical synthesis
Pyrazoles / chemistry*
Pyrazoles / pharmacology
Receptors, Lysosphingolipid / agonists*
Receptors, Lysosphingolipid / metabolism
Stereoisomerism
Structure-Activity Relationship

Substances

Bicyclic Monoterpenes
Monoterpenes
Pyrazoles
Receptors, Lysosphingolipid
pyrazole
3-carene