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

Chemistry Around Imidazopyrazine And Ibuprofen: Discovery Of Novel Fatty Acid Amide Hydrolase (FAAH) Inhibitors.

Frédéric De Wael, G. Muccioli, Didier M. Lambert, T. Sergent, Yves-Jacques Schneider, J. Rees, J. Marchand-Brynaert
Published 2010 · Chemistry, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
Based on the imidazo-[1,2-a]-pyrazin-3-(7H)-one scaffold, a dual action prodrug has been designed for combining antioxidant and anti-inflammatory activities, possibly unmasked upon oxidation. The construction of the target-molecule requires two building blocks, namely a 2-amino-1,4-pyrazine and a 2-ketoaldehyde. Attempts to synthesize the 2-ketoaldehyde (5a) derived from ibuprofen failed, but led to the corresponding 2-ketoaldoxime (7a) which could not be condensed with the pyrazine synthons. However, a model compound, i.e. phenylglyoxal aldoxime, reacted well under microwave activation to furnish novel imidazo[1,2-a]-pyrazine-3-(7H)-imine derivatives (18a,b). These heterobicycles behave as antioxidants by inhibiting the lipid peroxidation, and one compound (18b) is endowed with a significant anti-inflammatory effect in a cellular test. Unexpectedly, all the synthetic intermediates derived from ibuprofen are good inhibitors of FAAH, the most active compound (4a) featuring the 1,3-dithian-2-yl motif.
This paper references
10.1021/jm9008532
beta-Lactams derived from a carbapenem chiron are selective inhibitors of human fatty acid amide hydrolase versus human monoacylglycerol lipase.
Marion Feledziak (2009)
10.1515/9783111576855-015
J
Seguin Hen (1824)
10.3998/ARK.5550190.0003.B05
An efficient conversion of carboxylic acids into Weinreb amides
A. Katritzky (2002)
10.2174/1389557043403927
Discovery and validation of a new family of antioxidants: the aminopyrazine derivatives.
M. Dubuissona (2004)
10.1002/CHIN.200151158
Imidazolopyrazinones as Potential Antioxidants.
I. Devillers (2001)
10.1021/JO000792F
N-Acylbenzotriazoles: neutral acylating reagents for the preparation of primary, secondary, and tertiary amides
M. Katritzky (2000)
10.1016/S0009-3084(00)00196-1
Endocannabinoids and fatty acid amides in cancer, inflammation and related disorders.
L. De Petrocellis (2000)
10.1016/J.BBRC.2006.12.233
Imidazole-assisted catalysis of luminescence reaction in blue fluorescent protein from the photoprotein aequorin.
S. Inouye (2007)
10.1021/JM050977K
Substituted 2-thioxoimidazolidin-4-ones and imidazolidine-2,4-diones as fatty acid amide hydrolase inhibitors templates.
G. Muccioli (2006)
10.1039/C39940002405
Synthesis and preliminary chemie- and bio-iuminescence studies of a novel photolabile coelenterazine analogue with a trifluoromethyl diazirine group
F. Chen (1994)
10.1002/CHIN.197512219
REACTIVITY OF N-2-(1,1-DICHLOROALKYLIDENE)CYCLOHEXYLAMINES PART 2
N. Kimpe (1975)
10.1002/CHIN.198301180
Preparation of 1,1‐Dialkoxy‐2‐alkanones.
R. Verhé (1982)
10.1039/b103282h
Protecting groups
K. Jarowicki (1999)
10.1017/S0007114508966666
Modulation of signalling nuclear factor-kappaB activation pathway by polyphenols in human intestinal Caco-2 cells.
Béatrice Romier (2008)
10.1021/AR7000843
Hybrid molecules with a dual mode of action: dream or reality?
B. Meunier (2008)
Inhibition of fatty acid amide hydrolase
S. Holt (2007)
10.1080/03639040500271803
Coelenterazine (Marine Bioluminescent Substrate): A Source of Inspiration for the Discovery of Novel Antioxidants
M. Dubuisson (2005)
10.1016/S0040-4039(00)88528-7
New synthetic ‘tricks’. A novel one-pot procedure for the conversion of primary nitro groups into aldehydes
Feélix Urpí (1990)
Review: novel cannabinoid receptors
A. J. Brown (2007)
A . J . Brown , Review : novel cannabinoid receptors
C. Michaux Feledziak (2007)
10.1021/ol901275n
Regio- and chemoselective multiple functionalization of chloropyrazine derivatives. Application to the synthesis of coelenterazine.
M. Mosrin (2009)
10.1021/JO051231X
α-Nitro Ketone Synthesis Using N-Acylbenzotriazoles
A. Katritzky (2005)
10.1021/JM0209679
Modifications of the ethanolamine head in N-palmitoylethanolamine: synthesis and evaluation of new agents interfering with the metabolism of anandamide.
S. Vandevoorde (2003)
10.1080/1071576021000036443
Synthesis, Structure-activity Relationship and In Vitro Evaluation of Coelenterazine and Coelenteramine Derivatives as Inhibitors of Lipid Peroxidation
M. Burton (2003)
10.1002/CHIN.200330185
N-(Alkyl)-2-amino-1,4-pyrazine Derivatives: Synthesis and Antioxidative Properties of 3- and 3,5-p-Hydroxyphenyl-Substituted Compounds.
Paul Jeanjot (2003)
10.1515/9783111697888-004
B
B. A. R. Kernfach (1824)
10.1016/J.TET.2005.04.025
Synthesis of azide-fluoro-dehydrocoelenterazine analog as a photoaffinity-labeling probe and photolysis of azide-fluoro-coelenterazine
M. Kuse (2005)
10.1016/j.bmc.2009.05.025
In vitro and in vivo studies of 6,8-(diaryl)imidazo[1,2-a]pyrazin-3(7H)-ones as new antioxidants.
Frédéric De Wael (2009)
10.1038/sj.bjp.0706510
Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models
A. Jayamanne (2006)
Ibuprofen inhibits rat brain deamidation of anandamide at pharmacologically relevant concentrations. Mode of inhibition and structure-activity relationship.
C. Fowler (1997)
10.1515/9783111548050-024
M
M. Sankar (1824)
10.1016/S0223-5234(03)00074-6
Synthesis of ibuprofen heterocyclic amides and investigation of their analgesic and toxicological properties.
M. Cocco (2003)
10.1016/J.TET.2003.11.016
Recent synthetic developments in the nitro to carbonyl conversion (Nef reaction)
R. Ballini (2004)
10.1016/0040-4020(93)80013-J
Mass spectrometric studies on chemiluminescence of coelenterate luciferin analogues
T. Hirano (1993)
10.1021/JO00363A007
Formation of the tetracyclo[5.4.2.02,6.02,9]tridecane ring system by a novel transannular aldolization reaction
M. Deshpande (1986)
10.1124/MOL.51.4.576
Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen.
C. Reichel (1997)
10.1021/jm800311k
Discovery and development of fatty acid amide hydrolase (FAAH) inhibitors.
M. Seierstad (2008)
10.1002/cbic.200700139
Disulfiram is an Inhibitor of Human Purified Monoacylglycerol Lipase, the Enzyme Regulating 2‐Arachidonoylglycerol Signaling
G. Labar (2007)
10.1039/A900289H
Synthesis, structural characterization and antioxidative properties of aminopyrazine and imidazolopyrazine derivatives
I. Devillers (1999)
10.1016/S0040-4020(01)88717-2
Synthèse de cétones α, α′-fonctionnalisées puis d'aldéhydes α-énols par ouverture des α-cyano α-hydroxyméthyl époxydes.
K. Layachi (1992)
10.1039/P19950002129
A potential photoaffinity probe for labelling the active site of aequorin: a photolabile coelenterazine analogue with a trifluoromethyldiazirine group
F. Q. Chen (1995)
10.1002/(SICI)1098-2299(199905)47:1<9::AID-DDR2>3.0.CO;2-9
Synthesis and pharmacological evaluation of novel derivatives of anti‐inflammatory drugs with increased antioxidant and anti‐inflammatory activities
A. Kourounakis (1999)
10.1007/3-540-26367-5_1
A
A. Spring (2005)
10.1038/sj.bjp.0706406
Cannabinoid pharmacology: the first 66 years
R. Pertwee (2006)
10.1080/1475636021000049726
Acidic Nonsteroidal Anti-inflammatory Drugs Inhibit Rat Brain Fatty Acid Amide Hydrolase in a pH-dependent Manner
C. Fowler (2003)
10.1002/CHIN.199019112
A Fast Procedure for the Reduction of Azides and Nitro Compounds Based on the Reducing Ability of Sn(SR)- 3 Species.
M. Bartra (1990)
10.1016/S0040-4020(00)00163-0
Synthesis of 13C-Dehydrocoelenterazine and NMR Studies on the Bioluminescence of a Symplectoteuthis Model
M. Kuse (2000)
10.1039/A607460J
Highly efficient and flexible total synthesis of coelenterazine
M. Keenan (1997)
10.1055/S-2003-37652
N-(alkyl)-2-amino-1,4-pyrazine derivatives: Synthesis and antioxidative properties of 3-and 3,5-p-hydroxyphenyl-substituted compounds
Paul Jeanjot (2003)
10.1002/BSCB.19740831113
Reactivity of N‐2‐(1,1‐Dichloroalkylidene) Cyclohexylamines. II
Norbert de Kimpe (2010)
10.1016/S0040-4020(02)00100-X
19F-Dehydrocoelenterazine as probe to investigate the active site of symplectin
M. Isobe (2002)
10.1093/MILMED/151.1.386
Goodman and Gilman's the Pharmacological Basis of Therapeutics
W. Stigelman (1986)
10.1016/J.BMCL.2004.05.025
Synthesis and pharmacological evaluation of amide conjugates of NSAIDs with L-cysteine ethyl ester, combining potent antiinflammatory and antioxidant properties with significantly reduced gastrointestinal toxicity.
D. Galanakis (2004)
10.1177/026119290102900604
In Vitro Models of the Intestinal Barrier
E. Le Ferrec (2001)
10.1021/jm801042a
Synthesis and evaluation of benzothiazole-based analogues as novel, potent, and selective fatty acid amide hydrolase inhibitors.
X. Wang (2009)
10.1007/s00535-009-0102-2
Present status and strategy of NSAIDs-induced small bowel injury
K. Higuchi (2009)
10.2174/092986707780831168
Dual action-based approaches to antibacterial agents.
J. Bremner (2007)
10.1021/JO00302A012
Selenium-catalyzed conversion of methyl ketones into .alpha.-keto acetals
M. Tiecco (1990)
10.1006/ABBI.1998.1025
Inhibition of anandamide hydrolysis by the enantiomers of ibuprofen, ketorolac, and flurbiprofen.
C. Fowler (1999)
10.1016/S0040-4039(01)96396-8
A new synthetic method for aromatic α-oxo aldehydes : friedel-crafts reaction
Moitra Sk (1971)
10.1515/9783111438443-006
N
Città DI Torino (1824)
10.1016/j.drudis.2009.08.002
Pain and beyond: fatty acid amides and fatty acid amide hydrolase inhibitors in cardiovascular and metabolic diseases.
Sivaram Pillarisetti (2009)
10.1021/bp050208u
Role of Caco‐2 Cell Monolayers in Prediction of Intestinal Drug Absorption
Pranav J. Shah (2006)
10.1038/sj.bjp.0704113
Effects of pH on the inhibition of fatty acid amidohydrolase by ibuprofen
S. Holt (2001)
10.1016/J.EJPHAR.2007.02.051
Inhibition of fatty acid amide hydrolase, a key endocannabinoid metabolizing enzyme, by analogues of ibuprofen and indomethacin.
S. Holt (2007)
10.1002/CHIN.199225120
Synthesis of α,α′-Functionalized Ketones and α-Enol Aldehydes by Opening of α-Cyano-α-hydroxymethyl Epoxides.
K. Layachi (1992)
10.1111/J.1600-0773.1997.TB00291.X
Ibuprofen inhibits the metabolism of the endogenous cannabimimetic agent anandamide.
C. Fowler (1997)
New synthetic method for aromatic a-oxo aldehydes: FriedeleCrafts reaction
S. K. Moitra (1971)
Synthesis of a , a 0 - functionalized ketone intermediates for a - enol aldehydes by ring opening of a - cyano a - hydroxymethyl epoxides
I. Ariès-Gautron Layachi (1992)
10.1006/ABBI.1998.1078
Application of a thermodynamic model to the prediction of phase separations in freeze-concentrated formulations for protein lyophilization.
M. Heller (1999)
10.1016/J.BCP.2006.07.004
Regulation of inflammation and redox signaling by dietary polyphenols.
I. Rahman (2006)
10.1016/S0040-4039(00)88527-5
New synthetic ‘tricks’. Direct conversion of nitro compounds to nitriles
F. Urpí (1990)



This paper is referenced by
10.1002/JHET.2736
Design, Synthesis, and Molecular Docking Studies of Pyrazine Containing 1,2,3-Triazole Derivatives
Radhakrishnam Raju Ruddarraju (2017)
10.1039/c4ob01380h
Recent advances in development of imidazo[1,2-a]pyrazines: synthesis, reactivity and their biological applications.
R. Goel (2015)
10.1016/j.molstruc.2019.127040
Synthesis, characterisation, crystal structures, anticoagulant and antiplatelet activity studies of new 2,6-dipyrazinylpyridines with pendant trimethoxyphenyl
Garlapati Ramesh (2020)
10.1080/14756366.2020.1743283
Exploring the fatty acid amide hydrolase and cyclooxygenase inhibitory properties of novel amide derivatives of ibuprofen
Alessandro Deplano (2020)
10.1016/j.tips.2012.05.003
NSAIDs: eNdocannabinoid stimulating anti-inflammatory drugs?
C. Fowler (2012)
10.1016/J.MOLSTRUC.2014.05.042
Supramolecular interactions in biologically relevant compounds. 2-Pyrazineformamide thiosemicarbazones and some products of their cyclization
A. Castiñeiras (2014)
10.1039/C6RA03068H
Coordination chemistry of pyrazine derivatives analogues of PZA: design, synthesis, characterization and biological activity
M. Ogryzek (2016)
10.1088/2399-6528/AAAEE6
Dielectric dispersion, relaxation and molecular interaction of pyrazine binary mixtures
P. Senthilkumar (2018)
10.1002/ADSC.201500008
The Nitro to Carbonyl Conversion (Nef Reaction): New Perspectives for a Classical Transformation
R. Ballini (2015)
The endocannabinoid system : a translational study from Achilles tendinosis to cyclooxygenase
Emmelie Björklund (2014)
10.1002/ejoc.201901511
Divergent Access to Imidazopyrazinones and Imidazodiazepinones by Regioswitchable Post‐Ugi Heteroannulation
Danjun Wu (2019)
10.1371/journal.pone.0103589
Inhibition of Endocannabinoid Metabolism by the Metabolites of Ibuprofen and Flurbiprofen
Jessica Karlsson (2014)
10.1016/j.bmcl.2014.10.064
Inhibition of FAAH, TRPV1, and COX2 by NSAID-serotonin conjugates.
Tyler M. Rose (2014)
10.1007/7081_2015_179
Preparation, Reactivity, and Synthetic Utility of Simple Benzotriazole Derivatives
Romaric Gérardy (2015)
10.1371/journal.pone.0142711
Interaction of the N-(3-Methylpyridin-2-yl)amide Derivatives of Flurbiprofen and Ibuprofen with FAAH: Enantiomeric Selectivity and Binding Mode
Jessica Karlsson (2015)
10.2174/157488912798842223
Inhibitors of the endocannabinoid-degrading enzymes, or how to increase endocannabinoid's activity by preventing their hydrolysis.
Marion Feledziak (2012)
10.1021/jm400923s
Chiral 1,3,4-oxadiazol-2-ones as highly selective FAAH inhibitors.
Jayendra Z. Patel (2013)
10.1038/s41598-020-63605-4
Synthesis, cytotoxicity, pharmacokinetic profile, binding with DNA and BSA of new imidazo[1,2-a]pyrazine-benzo[d]imidazol-5-yl hybrids
I. Singh (2020)
10.1016/J.TET.2012.12.055
2-Alkoxy- and 2-alkylthio-2-alkenals in the reactions of electrophilic and nucleophilic addition. DFT study and NBO analysis
N. A. Keiko (2013)
10.5152/CLINEXPHEALTHSCI.2016.024
Bazı İmidazo[1,2-a]pirazin Türevlerinin Sentezi ve Antinosiseptif Aktivitelerinin Değerlendirilmeleri
Guelhan Turan‐Zitouni (2016)
10.5152/clinexphealthsci.2016.024
Synthesis of Some Imidazo [ 1 , 2-a ] pyrazine Derivatives and Evaluation of Their Antinociceptive Activity
Guelhan Turan‐Zitouni (2016)
10.3109/14756366.2011.643304
Inhibitory properties of ibuprofen and its amide analogues towards the hydrolysis and cyclooxygenation of the endocannabinoid anandamide
C. Fowler (2013)
Semantic Scholar Logo Some data provided by SemanticScholar