Online citations, reference lists, and bibliographies.
← Back to Search

Benzylamides And Piperazinoarylamides Of Ibuprofen As Fatty Acid Amide Hydrolase Inhibitors

Alessandro Deplano, Mariateresa Cipriano, Federica Moraca, E. Novellino, B. Catalanotti, C. Fowler, V. Onnis
Published 2019 · Chemistry, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Abstract Fatty Acid Amide Hydrolase (FAAH) is a serine hydrolase that plays a key role in controlling endogenous levels of endocannabinoids. FAAH inhibition is considered a powerful approach to enhance the endocannabinoid signalling, and therefore it has been largely studied as a potential target for the treatment of neurological disorders such as anxiety or depression, or of inflammatory processes. We present two novel series of amide derivatives of ibuprofen designed as analogues of our reference FAAH inhibitor Ibu-AM5 to further explore its structure-activity relationships. In the new amides, the 2-methylpyridine moiety of Ibu-AM5 was substituted by benzylamino and piperazinoaryl moieties. The obtained benzylamides and piperazinoarylamides showed FAAH inhibition ranging from the low to high micromolar potency. The binding of the new amides in the active site of FAAH, estimated using the induced fit protocol, indicated arylpiperazinoamides binding the ACB channel and the cytosolic port, and benzylamides binding the ACB channel.
This paper references
Tanezumab takes on pain due to osteoarthritis of the knee
Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474
Annelot C. M. van Esbroeck (2017)
Patients’ Responsibilities in Medical Ethics
Zhu Fengqing (2016)
Fatty acid amide hydrolase inhibitors: a patent review
A Lodola (2009)
Therapeutic Potential of Fatty Acid Amide Hydrolase, Monoacylglycerol Lipase, and N-Acylethanolamine Acid Amidase Inhibitors.
Wei Tuo (2017)
Fatty Acid Amide Hydrolase Inhibitor Treatment in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Adaptive Double-blind, Randomized Controlled Trial.
F. Wagenlehner (2017)
Computational insights into function and inhibition of fatty acid amide hydrolase.
G. Palermo (2015)
The potential of inhibitors of endocannabinoid metabolism as anxiolytic and antidepressive drugs—A practical view
C. Fowler (2015)
Radiosynthesis and Evaluation of [11C-Carbonyl]-Labeled Carbamates as Fatty Acid Amide Hydrolase Radiotracers for Positron Emission Tomography
A. Wilson (2013)
A simple stopped assay for fatty acid amide hydrolase avoiding the use of a chloroform extraction phase.
L. Boldrup (2004)
Fatty Acid Amide Hydrolase Inhibition Heightens Anandamide Signaling Without Producing Reinforcing Effects in Primates
Z. Justinova (2008)
and Drug Administration
US Foo (2016)
The endocannabinoid system as a target for novel anxiolytic drugs
S. Patel (2017)
Identification of potent, noncovalent fatty acid amide hydrolase (FAAH) inhibitors.
Darin J. Gustin (2011)
Modulation of anxiety through blockade of anandamide hydrolysis
S. Kathuria (2003)
Interaction of the N-(3-Methylpyridin-2-yl)amide Derivatives of Flurbiprofen and Ibuprofen with FAAH: Enantiomeric Selectivity and Binding Mode
Jessica Karlsson (2015)
Schr€ odinger Suite 2017-1 Induced Fit Docking protocol
Experimental colitis in mice is attenuated by changes in the levels of endocannabinoid metabolites induced by selective inhibition of fatty acid amide hydrolase (FAAH).
M. Salaga (2014)
Structure and function of fatty acid amide hydrolase.
M. K. McKinney (2005)
Epik: a software program for pKa prediction and protonation state generation for drug-like molecules
J. Shelley (2007)
Ibuprofen inhibits rat brain deamidation of anandamide at pharmacologically relevant concentrations. Mode of inhibition and structure-activity relationship.
C. Fowler (1997)
Inhibitory properties of ibuprofen and its amide analogues towards the hydrolysis and cyclooxygenation of the endocannabinoid anandamide
C. Fowler (2013)
Structural Adaptations in a Membrane Enzyme That Terminates Endocannabinoid Signaling
M. Bracey (2002)
Novel procedure for modeling ligand/receptor induced fit effects.
W. Sherman (2006)
Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments
G. M. Sastry (2013)
Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor.
Angelo D. Favia (2012)
Synthesis of ibuprofen heterocyclic amides and investigation of their analgesic and toxicological properties.
M. Cocco (2003)
Inhibition of fatty acid amide hydrolase, a key endocannabinoid metabolizing enzyme, by analogues of ibuprofen and indomethacin.
S. Holt (2007)
Safety, Tolerability and Pharmacokinetics of FAAH Inhibitor V158866: A Double-Blind, Randomised, Placebo-Controlled Phase I Study in Healthy Volunteers
Stephen Pawsey (2016)
Novel propanamides as fatty acid amide hydrolase inhibitors.
Alessandro Deplano (2017)
Vernalis plc Completes Investment in its NCE Development [press release
P. Vernalis (2015)
Epik: a software program for pK(a) prediction and protonation state generation for JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY 575 drug-like molecules
JC Shelley (2007)
An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee
J. P. Huggins (2012)
Targeting endocannabinoid degradation protects against experimental colitis in mice: involvement of CB1 and CB2 receptors
M. Storr (2008)
Stenstr€ om A. Ibuprofen inhibits rat brain deamidation of anandamide at pharmacologically relevant concentrations. Mode of inhibition and structureactivity relationship
C J Fowler (1997)
Carbonyl-labeled carbamates as fatty acid amide hydrolase radiotracers for positron emission tomography
AA Wilson (2013)
Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects.
G. L. Li (2012)
Inhibition of anandamide hydrolysis by the enantiomers of ibuprofen, ketorolac, and flurbiprofen.
C. Fowler (1999)
New approaches and challenges to targeting the endocannabinoid system
V. Marzo (2018)
FDA works with regulatory partners to understand French-based Biotrial phase 1 clinical study
Fatty acid amide hydrolase inhibitors: a patent review (2009 – 2014)
A. Lodola (2015)

This paper is referenced by
Semantic Scholar Logo Some data provided by SemanticScholar