(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
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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
References
1. DE Vivi M, Scaparelli R, Cavalli A, Migliore M, Piomelli D, Habrant D, Favia. (2014)
Multitarget FAAH and COX inhibitors and therapeutical uses thereof.
Patent number: WO2014023643 A1. Assignee: Fondazione Istituto Italiano Di Tecnologia. Priority date: 06/08/2012. Publication date: 13/02/2014.
2. Grim TW, Ghosh S, Hsu KL, Cravatt BF, Kinsey SG, Lichtman AH. (2014)
Combined inhibition of FAAH and COX produces enhanced anti-allodynic effects in mouse neuropathic and inflammatory pain models.
Pharmacol. Biochem. Behav., 124: 405-11. [PMID:25058512]
3. Migliore M, Habrant D, Sasso O, Albani C, Bertozzi SM, Armirotti A, Piomelli D, Scarpelli R. (2016)
Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies.
Eur J Med Chem, 109: 216-37. [PMID:26774927]
4. Palermo G, Favia AD, Convertino M, De Vivo M. (2016)
The Molecular Basis for Dual Fatty Acid Amide Hydrolase (FAAH)/Cyclooxygenase (COX) Inhibition.
ChemMedChem, 11 (12): 1252-8. [PMID:26593700]
5. Sasso O, Migliore M, Habrant D, Armirotti A, Albani C, Summa M, Moreno-Sanz G, Scarpelli R, Piomelli D. (2015)
Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage.
FASEB J., 29 (6): 2616-27. [PMID:25757568]