(S)-ARN2508   

GtoPdb Ligand ID: 8999

Synonyms: compound (+)-10r [PMID: 26774927] | example 20 [WO2014023643]
Compound class: Synthetic organic
Comment: (S)-ARN2508 is a dual inhibitor of fatty acid amide hydrolase (FAAH) and COX enzyme activities [3], claimed in patent WO2014023643 [1]. The compound series developed by Migliore et al. (2015) [3] is based on a hybrid scaffold combining structural motifs of the FAAH inhibitor URB597 and the COX inhibitor flurbiprofen. From this series, the (S) enantiomer was found to inhibit both enzymes, whereas the (R) enantiomer ((R)-ARN2508) only inhibited FAAH.
2D Structure
Click here for structure editor
Physico-chemical Properties
Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 75.63
Molecular weight 387.18
XLogP 5.68
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
Canonical SMILES CCCCCCNC(=O)Oc1cccc(c1)c1ccc(cc1F)C(C(=O)O)C
Isomeric SMILES CCCCCCNC(=O)Oc1cccc(c1)c1ccc(cc1F)[C@@H](C(=O)O)C
InChI InChI=1S/C22H26FNO4/c1-3-4-5-6-12-24-22(27)28-18-9-7-8-17(13-18)19-11-10-16(14-20(19)23)15(2)21(25)26/h7-11,13-15H,3-6,12H2,1-2H3,(H,24,27)(H,25,26)/t15-/m0/s1
InChI Key USQOVYLRWBOSQC-HNNXBMFYSA-N
Bioactivity Comments
When tested, the racemic mixture of (R) and (S) ARN2508 (compound 10r in [3]) gave IC50 values of 31nM for FAAH, 12nM for COX1 and 430nM for COX2 [3]. Note that the (S) enantiomer is the much more potent COX inhibitor, being ~14000 times more potent for COX1 and 1900 times more potent for COX2 than the (R) enantiomer.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
COX-1 Hs Inhibitor Inhibition 9.5 pIC50 - 3
pIC50 9.5 (IC50 2.9x10-10 M) [3]
Fatty acid amide hydrolase Hs Inhibitor Inhibition 8.0 pIC50 - 3
pIC50 8.0 (IC50 9.4x10-9 M) [3]
COX-2 Hs Inhibitor Inhibition 7.9 pIC50 - 3
pIC50 7.9 (IC50 1.2x10-8 M) [3]