Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Mini Reviews in Medicinal Chemistry
  4. Fast Track Articles
  5. Fast Track Article
image of Promising Inhibitors of Endocannabinoid Degrading Enzymes Sharing a Carbamate Scaffold

Abstract

Carbamate has been extensively used as a scaffold in the recent era of drug discovery and is a common structural motif of many approved drugs. The carbamate moiety's unique amide-ester hybrid (-O-CO-NH-) feature offers the designing of specific drug-target interactions. Despite the discovery of numerous carbamate derivatives that act on the endocannabinoid system (ECS), the development of clinically effective carbamates remains a challenge. In this review, we highlight the therapeutic potential of carbamate inhibitors of endocannabinoid degrading enzymes as a breakthrough in discovering neurotherapeutic drugs. We discuss the design strategies and medicinal chemistry aspects involved in developing carbamate-based molecular architectures that modulate the endocannabinoid signaling pathway by interfering with fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), and α/β-Hydrolase domain-containing 6 (ABHD6). Additionally, we highlight the dual activity profile of carbamates against FAAH and MAGL, FAAH and cholinesterase, and FAAH and TRPV1 channels. Furthermore, we illustrate the pharmacophores of -functionalized carbamates and N-cyclic carbamates that are crucial for FAAH and MAGL inhibitory activities, respectively.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575328120241107061303
2024-11-25
2024-12-26

  • From This Site

    /content/journals/mrmc/10.2174/0113895575328120241107061303
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Matošević A. Bosak A. Carbamate group as structural motif in drugs: A review of carbamate derivatives used as therapeutic agents. Arh. Hig. Rada Toksikoly. 2020 71 4 285 299 10.2478/aiht‑2020‑71‑3466 33410773
    [Google Scholar]
  2. Ghosh A.K. Brindisi M. Organic carbamates in drug design and medicinal chemistry. J. Med. Chem. 58 7 2895 2940 2015 10.1021/jm501371s
    [Google Scholar]
  3. Kaur D. Sharma P. Bharatam P.V. Amide resonance in thio- and seleno- carbamates: A theoretical study. J. Mol. Struct. Theochem 2005 757 1-3 149 153 10.1016/j.theochem.2005.09.019
    [Google Scholar]
  4. Deetz M.J. Forbes C.C. Jonas M. Malerich J.P. Smith B.D. Wiest O. Unusually low barrier to carbamate C-N rotation. J. Org. Chem. 2002 67 11 3949 3952 10.1021/jo025554u 12027723
    [Google Scholar]
  5. Dugave C. Chemical aspects of the restricted rotation of esters, amides, and related compounds. Cis‐trans Isomerization in Biochemistry Wiley Dugave C. 2006 143 166 10.1002/9783527609338.ch8
    [Google Scholar]
  6. Marcovici-Mizrahi D. Gottlieb H.E. Marks V. Nudelman A. On the stabilization of the syn-rotamer of amino acid carbamate derivatives by hydrogen bonding. J. Org. Chem. 1996 61 24 8402 8406 10.1021/jo961446u
    [Google Scholar]
  7. Chaturvedi D. Role of organic carbamates in anticancer drug design. Chemistry and Pharmacology of Naturally Occurring Bioactive Compounds CRC Press Brahmachari G. 1st ed 2013
    [Google Scholar]
  8. Jaiswal S. Ayyannan S.R. Anticancer potential of small molecule inhibitors of fatty acid amide hydrolase and monoacylglycerol lipase ‐ A mini‐review. ChemMedChem 2021 16 14 2172 2187 10.1002/cmdc.202100120
    [Google Scholar]
  9. Jaiswal S. Akhilesh Uniyal A. Tiwari V. Raja Ayyannan S. Synthesis and evaluation of dual fatty acid amide hydrolase-monoacylglycerol lipase inhibition and antinociceptive activities of 4-methylsulfonylaniline-derived semicarbazones. Bioorg. Med. Chem. 2022 60 116698 10.1016/j.bmc.2022.116698 35296453
    [Google Scholar]
  10. Jaiswal S. Raja Ayyannan S. Discovery of isatin-based carbohydrazones as potential dual inhibitors of fatty acid amide hydrolase and monoacylglycerol lipase. ChemMedChem 2021 10.1002/cmdc.202100120 34637598
    [Google Scholar]
  11. Niphakis M.J. Cognetta A.B. Chang J.W. Buczynski M.W. Parsons L.H. Byrne F. Burston J.J. Chapman V. Cravatt B.F. Evaluation of NHS carbamates as a potent and selective class of endocannabinoid hydrolase inhibitors. ACS Chem. Neurosci. 2013 4 9 1322 1332 10.1021/cn400116z 23731016
    [Google Scholar]
  12. Jaiswal S. Tripathi R.K.P. Ayyannan S.R. Scaffold hopping-guided design of some isatin based rigid analogs as fatty acid amide hydrolase inhibitors: Synthesis and evaluation. Biomed. Pharmacother. 2018 107 1611 1623 10.1016/j.biopha.2018.08.125 30257379
    [Google Scholar]
  13. Jaiswal S. Ayyannan S.R. Lead optimization study on indoline-2, 3-dione derivatives as potential fatty acid amide hydrolase inhibitors. J. Biomol. Struct. Dyn. 2022 ••• 1 19 36379672
    [Google Scholar]
  14. Feledziak M. Lambert D.M. Marchand-brynaert J. Muccioli G.G. Inhibitors of the endocannabinoid-degrading enzymes, or how to increase endocannabinoid's activity by preventing their hydrolysis. Recent Pat. CNS Drug Discov. 7 22 49 70 2012 10.2174/157488912798842223
    [Google Scholar]
  15. Basso E. Duranti A. Mor M. Piomelli D. Tontini A. Tarzia G. Traldi P. Tandem mass spectrometric data–FAAH inhibitory activity relationships of some carbamic acid O ‐aryl esters. J. Mass Spectrom. 2004 39 12 1450 1455 10.1002/jms.729 15578755
    [Google Scholar]
  16. Mileni M. Kamtekar S. Wood D.C. Benson T.E. Cravatt B.F. Stevens R.C. Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597: Discovery of a deacylating water molecule and insight into enzyme inactivation. J. Mol. Biol. 2010 400 4 743 754 10.1016/j.jmb.2010.05.034 20493882
    [Google Scholar]
  17. Sit S.Y. Conway C.M. Xie K. Bertekap R. Bourin C. Burris K.D. Oxime carbamate - Discovery of a series of novel FAAH inhibitors. Bioorg. Med. Chem. Lett. 2010 20 3 1272 1277 10.1016/j.bmcl.2009.11.080 20036536
    [Google Scholar]
  18. Caprioli A. Coccurello R. Rapino C. Di Serio S. Di Tommaso M. Vertechy M. Vacca V. Battista N. Pavone F. Maccarrone M. Borsini F. The novel reversible fatty acid amide hydrolase inhibitor ST4070 increases endocannabinoid brain levels and counteracts neuropathic pain in different animal models. J. Pharmacol. Exp. Ther. 2012 342 1 188 195 10.1124/jpet.111.191403 22514334
    [Google Scholar]
  19. Abouabdellah A. Görlitzer J. Hamley P. Ravet A. Alkylthiazol carbamate derivatives, preparation thereof and therapeutic use thereof. US Patent 8912218B2 2014
  20. Abouabdellah A. Chereze N. Fayol A. Saady M. Vache J. Veronique C. Yaiche P. Carbamate derivatives of alkyl-heterocycles, preparation thereof and therapeutic use thereof. US Patent 8716289B2 2014
  21. Abouabdellah A. Bas M. Dargazanli G. Hoornaert C. Li A.T. Medaisko F. Dioxane-2-alkylcarbamates, their preparation and use as fatty acid amido hydrolase (FAAH) inhibitors for treating faah-related pathologies. 2004
    [Google Scholar]
  22. Xie K. Preparation of bis arylimidazolyl fatty acid amide hydrolase inhibitors for treatment of pain. WO Patent 875692002 2002
  23. Myllymaeki M. Castillo-Melendez J. Koskinen A. Minkkilae A. Saario S. Nevalainen T. Jaervinen T. Poso A. Salo-Ahen O. Preparation of heterocyclic phenyl carbamates as novel FAAH inhibitors. WO Patent 2008129129 2008
  24. Ishii T. Sugane T. Maeda J. Narazaki F. Kakefuda A. Sato K. Takahashi T. Kanayama T. Saitoh C. Suzuki J. Preparation of pyridyl non-aromatic nitrogenated heterocyclic-1-carboxylate ester derivatives as FAAH inhibitors. WO patent 2006088075 2006
  25. Lodola A. Castelli R. Mor M. Rivara S. Fatty acid amide hydrolase inhibitors: A patent review (2009–2014). 2015 Expert Opin. Ther. Pat. 25 11 1247 1266 10.1517/13543776.2015.1067683
    [Google Scholar]
  26. Piomelli D. Moreno-Sanz G. Bandiera T. Mor M. Tarzia G. Meta-substituted biphenyl peripherally restricted FAAH inhibitors. US Patent 9745255B2 2017
  27. Piomelli D. Clapper J.R. Moreno-Sanz G. Duranti A. Tontini A. Mor M. Tarzia G. Peripherally restricted FAAH inhibitors. US Patent 9187413B2 2015
  28. Tarzia G. Duranti A. Tontini A. Piersanti G. Mor M. Rivara S. Plazzi P.V. Park C. Kathuria S. Piomelli D. Design, synthesis, and structure-activity relationships of alkylcarbamic acid aryl esters, a new class of fatty acid amide hydrolase inhibitors. J. Med. Chem. 2003 46 12 2352 2360 10.1021/jm021119g 12773040
    [Google Scholar]
  29. Mor M. Rivara S. Lodola A. Plazzi P.V. Tarzia G. Duranti A. Tontini A. Piersanti G. Kathuria S. Piomelli D. Cyclohexylcarbamic acid 3′- or 4′-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: Synthesis, quantitative structure-activity relationships, and molecular modeling studies. J. Med. Chem. 2004 47 21 4998 5008 10.1021/jm031140x 15456244
    [Google Scholar]
  30. Piomelli D. Tarzia G. Duranti A. Tontini A. Mor M. Compton T.R. Dasse O. Monaghan E.P. Parrott J.A. Putman D. Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). CNS Drug Rev. 2006 12 1 21 38 10.1111/j.1527‑3458.2006.00021.x 16834756
    [Google Scholar]
  31. Tarzia G. Duranti A. Gatti G. Piersanti G. Tontini A. Rivara S. Lodola A. Plazzi P.V. Mor M. Kathuria S. Piomelli D. Synthesis and structure-activity relationships of FAAH inhibitors: Cyclohexylcarbamic acid biphenyl esters with chemical modulation at the proximal phenyl ring. ChemMedChem 2006 1 1 130 139 10.1002/cmdc.200500017 16892344
    [Google Scholar]
  32. Mor M. Lodola A. Rivara S. Vacondio F. Duranti A. Tontini A. Sanchini S. Piersanti G. Clapper J.R. King A.R. Tarzia G. Piomelli D. Synthesis and quantitative structure-activity relationship of fatty acid amide hydrolase inhibitors: Modulation at the N-portion of biphenyl-3-yl alkylcarbamates. J. Med. Chem. 2008 51 12 3487 3498 10.1021/jm701631z 18507372
    [Google Scholar]
  33. Clapper J.R. Vacondio F. King A.R. Duranti A. Tontini A. Silva C. Sanchini S. Tarzia G. Mor M. Piomelli D. A second generation of carbamate-based fatty acid amide hydrolase inhibitors with improved activity in vivo. ChemMedChem 2009 4 9 1505 1513 10.1002/cmdc.200900210 19637155
    [Google Scholar]
  34. McKinney M.K. Cravatt B.F. Evidence for distinct roles in catalysis for residues of the serine-serine-lysine catalytic triad of fatty acid amide hydrolase. J. Biol. Chem. 2003 278 39 37393 37399 10.1074/jbc.M303922200 12734197
    [Google Scholar]
  35. Lodola A. Mor M. Hermann J.C. Tarzia G. Piomelli D. Mulholland A.J. QM/MM modelling of oleamide hydrolysis in fatty acid amide hydrolase (FAAH) reveals a new mechanism of nucleophile activation. Chem. Commun. (Camb.) 2005 35 4399 4401 10.1039/b503887a 16136230
    [Google Scholar]
  36. Lodola A. Capoferri L. Rivara S. Chudyk E. Sirirak J. Dyguda-Kazimierowicz E. Andrzej Sokalski W. Mileni M. Tarzia G. Piomelli D. Mor M. Mulholland A.J. Understanding the role of carbamate reactivity in fatty acid amide hydrolase inhibition by QM/MM mechanistic modelling. Chem. Commun. (Camb.) 2011 47 9 2517 2519 10.1039/c0cc04937a 21240393
    [Google Scholar]
  37. Clapper J.R. Moreno-Sanz G. Russo R. Guijarro A. Vacondio F. Duranti A. Tontini A. Sanchini S. Sciolino N.R. Spradley J.M. Hohmann A.G. Calignano A. Mor M. Tarzia G. Piomelli D. Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nat. Neurosci. 2010 13 10 1265 1270 10.1038/nn.2632 20852626
    [Google Scholar]
  38. Moreno-Sanz G. Sasso O. Guijarro A. Oluyemi O. Bertorelli R. Reggiani A. Piomelli D. Pharmacological characterization of the peripheral FAAH inhibitor URB937 in female rodents: Interaction with the Abcg2 transporter in the blood‐placenta barrier. Br. J. Pharmacol. 2012 167 8 1620 1628 10.1111/j.1476‑5381.2012.02098.x 22774772
    [Google Scholar]
  39. Fiorelli C. Scarpelli R. Piomelli D. Bandiera T. Development of a multigram synthesis of URB937, a peripherally restricted FAAH inhibitor. Org. Process Res. Dev. 2013 17 3 359 367 10.1021/op300301u
    [Google Scholar]
  40. Vozella V. Ahmed F. Choobchian P. Merrill C.B. Zibardi C. Tarzia G. Mor M. Duranti A. Tontini A. Rivara S. Piomelli D. Pharmacokinetics, pharmacodynamics and safety studies on URB937, a peripherally restricted fatty acid amide hydrolase inhibitor, in rats. J. Pharm. Pharmacol. 2019 71 12 1762 1773 10.1111/jphp.13166 31579946
    [Google Scholar]
  41. Moreno-Sanz G. Duranti A. Melzig L. Fiorelli C. Ruda G.F. Colombano G. Mestichelli P. Sanchini S. Tontini A. Mor M. Bandiera T. Scarpelli R. Tarzia G. Piomelli D. Synthesis and structure-activity relationship studies of O-biphenyl-3-yl carbamates as peripherally restricted fatty acid amide hydrolase inhibitors. J. Med. Chem. 2013 56 14 5917 5930 10.1021/jm4007017 23822179
    [Google Scholar]
  42. Alexander J.P. Cravatt B.F. Mechanism of carbamate inactivation of FAAH: Implications for the design of covalent inhibitors and in vivo functional probes for enzymes. Chem. Biol. 2005 12 11 1179 1187 10.1016/j.chembiol.2005.08.011 16298297
    [Google Scholar]
  43. Käsnänen H. Myllymäki M.J. Minkkilä A. Kataja A.O. Saario S.M. Nevalainen T. Koskinen A.M.P. Poso A. 3-Heterocycle-phenyl N-alkylcarbamates as FAAH inhibitors: Design, synthesis and 3D-QSAR studies. ChemMedChem 2010 5 2 213 231 10.1002/cmdc.200900390 20024981
    [Google Scholar]
  44. Myllymäki M.J. Saario S.M. Kataja A.O. Castillo-Melendez J.A. Nevalainen T. Juvonen R.O. Järvinen T. Koskinen A.M.P. Design, synthesis, and in vitro evaluation of carbamate derivatives of 2-benzoxazolyl- and 2-benzothiazolyl-(3-hydroxyphenyl)-methanones as novel fatty acid amide hydrolase inhibitors. J. Med. Chem. 2007 50 17 4236 4242 10.1021/jm070501w 17665899
    [Google Scholar]
  45. Myllymäki M.J. Käsnänen H. Kataja A.O. Lahtela-Kakkonen M. Saario S.M. Poso A. Koskinen A.M.P. Chiral 3-(4,5-dihydrooxazol-2-yl)phenyl alkylcarbamates as novel FAAH inhibitors: Insight into FAAH enantioselectivity by molecular docking and interaction fields. Eur. J. Med. Chem. 2009 44 10 4179 4191 10.1016/j.ejmech.2009.05.012 19539407
    [Google Scholar]
  46. Sit S.Y. Conway C. Bertekap R. Xie K. Bourin C. Burris K. Deng H. Novel inhibitors of fatty acid amide hydrolase. Bioorg. Med. Chem. Lett. 2007 17 12 3287 3291 10.1016/j.bmcl.2007.04.009 17459705
    [Google Scholar]
  47. Terwege T. Dahlhaus H. Hanekamp W. Lehr M. ω-Heteroarylalkylcarbamates as inhibitors of fatty acid amide hydrolase (FAAH). MedChemComm 2014 5 7 932 936 10.1039/C4MD00181H
    [Google Scholar]
  48. Forster L. Schulze Elfringhoff A. Lehr M. High-performance liquid chromatographic assay with fluorescence detection for the evaluation of inhibitors against fatty acid amide hydrolase. Anal. Bioanal. Chem. 2009 394 6 1679 1685 10.1007/s00216‑009‑2850‑5 19484225
    [Google Scholar]
  49. Boger D.L. Sato H. Lerner A.E. Hedrick M.P. Fecik R.A. Miyauchi H. Wilkie G.D. Austin B.J. Patricelli M.P. Cravatt B.F. Exceptionally potent inhibitors of fatty acid amide hydrolase: The enzyme responsible for degradation of endogenous oleamide and anandamide. Proc. Natl. Acad. Sci. USA 2000 97 10 5044 5049 10.1073/pnas.97.10.5044 10805767
    [Google Scholar]
  50. Terwege T. Hanekamp W. Garzinsky D. König S. Koch O. Lehr M. ω‐imidazolyl‐ and ω‐tetrazolylalkylcarbamates as inhibitors of fatty acid amide hydrolase: Biological activity and in vitro metabolic stability. ChemMedChem 2016 11 4 429 443 10.1002/cmdc.201500445 26732805
    [Google Scholar]
  51. Colombano G. Albani C. Ottonello G. Ribeiro A. Scarpelli R. Tarozzo G. Daglian J. Jung K.M. Piomelli D. Bandiera T. O-(triazolyl)methyl carbamates as a novel and potent class of fatty acid amide hydrolase (FAAH) inhibitors. ChemMedChem 2015 10 2 380 395 10.1002/cmdc.201402374 25338703
    [Google Scholar]
  52. Dahlhaus H. Hanekamp W. Lehr M. (Indolylalkyl)piperidine carbamates as inhibitors of fatty acid amide hydrolase (FAAH). MedChemComm 2017 8 3 616 620 10.1039/C6MD00683C 30108777
    [Google Scholar]
  53. Brindisi M. Borrelli G. Brogi S. Grillo A. Maramai S. Paolino M. Benedusi M. Pecorelli A. Valacchi G. Di Cesare Mannelli L. Ghelardini C. Allarà M. Ligresti A. Minetti P. Campiani G. di Marzo V. Butini S. Gemma S. Development of potent inhibitors of fatty acid amide hydrolase useful for the treatment of neuropathic pain. ChemMedChem 2018 13 19 2090 2103 10.1002/cmdc.201800397 30085402
    [Google Scholar]
  54. Lamani M. Malamas M.S. Farah S.I. Shukla V.G. Almeida M.F. Weerts C.M. Anderson J. Wood J.T. Farizatto K.L.G. Bahr B.A. Makriyannis A. Piperidine and piperazine inhibitors of fatty acid amide hydrolase targeting excitotoxic pathology. Bioorg. Med. Chem. 2019 27 23 115096 10.1016/j.bmc.2019.115096 31629610
    [Google Scholar]
  55. Gattinoni S. Simone C.D. Dallavalle S. Fezza F. Nannei R. Battista N. Minetti P. Quattrociocchi G. Caprioli A. Borsini F. Cabri W. Penco S. Merlini L. Maccarrone M. A new group of oxime carbamates as reversible inhibitors of fatty acid amide hydrolase. Bioorg. Med. Chem. Lett. 2010 20 15 4406 4411 10.1016/j.bmcl.2010.06.050 20591666
    [Google Scholar]
  56. Gattinoni S. De Simone C. Dallavalle S. Fezza F. Nannei R. Amadio D. Minetti P. Quattrociocchi G. Caprioli A. Borsini F. Cabri W. Penco S. Merlini L. Maccarrone M. Enol carbamates as inhibitors of fatty acid amide hydrolase (FAAH) endowed with high selectivity for FAAH over the other targets of the endocannabinoid system. ChemMedChem 2010 5 3 357 360 10.1002/cmdc.200900472 20112328
    [Google Scholar]
  57. Aghazadeh Tabrizi M. Baraldi P.G. Ruggiero E. Saponaro G. Baraldi S. Romagnoli R. Martinelli A. Tuccinardi T. Pyrazole phenylcyclohexylcarbamates as inhibitors of human fatty acid amide hydrolases (FAAH). Eur. J. Med. Chem. 2015 97 289 305 10.1016/j.ejmech.2015.04.064 26002335
    [Google Scholar]
  58. Griebel G. Stemmelin J. Lopez-Grancha M. Fauchey V. Slowinski F. Pichat P. Dargazanli G. Abouabdellah A. Cohen C. Bergis O.E. The selective reversible FAAH inhibitor, SSR411298, restores the development of maladaptive behaviors to acute and chronic stress in rodents. Sci. Rep. 2018 8 1 2416 10.1038/s41598‑018‑20895‑z 29403000
    [Google Scholar]
  59. Wilson A.A. Hicks J.W. Sadovski O. Parkes J. Tong J. Houle S. Fowler C.J. Vasdev N. Radiosynthesis and evaluation of [¹¹C-carbonyl]-labeled carbamates as fatty acid amide hydrolase radiotracers for positron emission tomography. J. Med. Chem. 2013 56 1 201 209 10.1021/jm301492y 23214511
    [Google Scholar]
  60. Cramer S. Johnson J. Ngo T. El-Alfy A.T. Stec J. Modulation of the endocannabinoid system via inhibition of fatty acid amide hydrolase (FAAH) by novel urea and carbamate derivatives. ChemistrySelect 2019 4 39 11609 11614 10.1002/slct.201903375
    [Google Scholar]
  61. Grillo A. Fezza F. Chemi G. Colangeli R. Brogi S. Fazio D. Federico S. Papa A. Relitti N. Di Maio R. Giorgi G. Lamponi S. Valoti M. Gorelli B. Saponara S. Benedusi M. Pecorelli A. Minetti P. Valacchi G. Butini S. Campiani G. Gemma S. Maccarrone M. Di Giovanni G. Selective fatty acid amide hydrolase inhibitors as potential novel antiepileptic agents. ACS Chem. Neurosci. 2021 12 9 1716 1736 10.1021/acschemneuro.1c00192 33890763
    [Google Scholar]
  62. Papa A. Pasquini S. Galvani F. Cammarota M. Contri C. Carullo G. Gemma S. Ramunno A. Lamponi S. Gorelli B. Saponara S. Varani K. Mor M. Campiani G. Boscia F. Vincenzi F. Lodola A. Butini S. Development of potent and selective FAAH inhibitors with improved drug-like properties as potential tools to treat neuroinflammatory conditions. Eur. J. Med. Chem. 2023 246 114952 10.1016/j.ejmech.2022.114952 36462439
    [Google Scholar]
  63. Bertrand T. Augé F. Houtmann J. Rak A. Vallée F. Mikol V. Berne P.F. Michot N. Cheuret D. Hoornaert C. Mathieu M. Structural basis for human monoglyceride lipase inhibition. J. Mol. Biol. 2010 396 3 663 673 10.1016/j.jmb.2009.11.060 19962385
    [Google Scholar]
  64. Labar G. Bauvois C. Borel F. Ferrer J.L. Wouters J. Lambert D.M. Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling. ChemBioChem 2010 11 2 218 227 10.1002/cbic.200900621 19957260
    [Google Scholar]
  65. McAllister L.A. Butler C.R. Mente S. O’Neil S.V. Fonseca K.R. Piro J.R. Cianfrogna J.A. Foley T.L. Gilbert A.M. Harris A.R. Helal C.J. Johnson D.S. Montgomery J.I. Nason D.M. Noell S. Pandit J. Rogers B.N. Samad T.A. Shaffer C.L. da Silva R.G. Uccello D.P. Webb D. Brodney M.A. Discovery of trifluoromethyl glycol carbamates as potent and selective covalent monoacylglycerol lipase (MAGL) inhibitors for treatment of neuroinflammation. J. Med. Chem. 2018 61 7 3008 3026 10.1021/acs.jmedchem.8b00070 29498843
    [Google Scholar]
  66. Long J.Z. Jin X. Adibekian A. Li W. Cravatt B.F. Characterization of tunable piperidine and piperazine carbamates as inhibitors of endocannabinoid hydrolases. J. Med. Chem. 2010 53 4 1830 1842 10.1021/jm9016976 20099888
    [Google Scholar]
  67. Granchi C. Caligiuri I. Minutolo F. Rizzolio F. Tuccinardi T. A patent review of Monoacylglycerol Lipase (MAGL) inhibitors (2013-2017). Expert Opin. Ther. Pat. 27 12 2017 1341 1351 10.1080/13543776.2018.1389899
    [Google Scholar]
  68. Chang J.W. Niphakis M.J. Lum K.M. Cognetta A.B. Wang C. Matthews M.L. Niessen S. Buczynski M.W. Parsons L.H. Cravatt B.F. Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates. Chem. Biol. 2012 19 5 579 588 10.1016/j.chembiol.2012.03.009 22542104
    [Google Scholar]
  69. Szabo M. Agostino M. Malone D.T. Yuriev E. Capuano B. The design, synthesis and biological evaluation of novel URB602 analogues as potential monoacylglycerol lipase inhibitors. Bioorg. Med. Chem. Lett. 2011 21 22 6782 6787 10.1016/j.bmcl.2011.09.038 21982493
    [Google Scholar]
  70. Hohmann A.G. Suplita R.L. Bolton N.M. Neely M.H. Fegley D. Mangieri R. Krey J.F. Michael Walker J. Holmes P.V. Crystal J.D. Duranti A. Tontini A. Mor M. Tarzia G. Piomelli D. An endocannabinoid mechanism for stress-induced analgesia. Nature 2005 435 7045 1108 1112 10.1038/nature03658 15973410
    [Google Scholar]
  71. Long J.Z. Li W. Booker L. Burston J.J. Kinsey S.G. Schlosburg J.E. Serrano A.M. Selley D.E. Parsons L.H. Lichtman A.H. Cravatt B.F. 2009 Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat. Chem. Biol. 5 1 37 44 10.1038/nchembio.129
    [Google Scholar]
  72. Kapanda C.N. Masquelier J. Muccioli G.G. Poupaert J.H. Lambert D.M. Synthesis and pharmacological evaluation of 2,4-dinitroaryldithiocarbamate derivatives as novel monoacylglycerol lipase inhibitors. J. Med. Chem. 55 12 5774 5783 2012 10.1021/jm3006004
    [Google Scholar]
  73. Chang J.W. Cognetta A.B. Niphakis M.J. Cravatt B.F. Proteome-wide reactivity profiling identifies diverse carbamate chemotypes tuned for serine hydrolase inhibition. ACS Chem. Biol. 2013 8 7 1590 1599 10.1021/cb400261h 23701408
    [Google Scholar]
  74. Griebel G. Pichat P. Beeské S. Leroy T. Redon N. Jacquet A. Françon D. Bert L. Even L. Lopez-Grancha M. Tolstykh T. Sun F. Yu Q. Brittain S. Arlt H. He T. Zhang B. Wiederschain D. Bertrand T. Houtmann J. Rak A. Vallée F. Michot N. Augé F. Menet V. Bergis O.E. George P. Avenet P. Mikol V. Didier M. Escoubet J. Selective blockade of the hydrolysis of the endocannabinoid 2-arachidonoylglycerol impairs learning and memory performance while producing antinociceptive activity in rodents. Sci. Rep. 2015 5 1 7642 10.1038/srep07642 25560837
    [Google Scholar]
  75. Cisar J.S. Weber O.D. Clapper J.R. Blankman J.L. Henry C.L. Simon G.M. Alexander J.P. Jones T.K. Ezekowitz R.A.B. O’Neill G.P. Grice C.A. Identification of ABX-1431, a selective inhibitor of monoacylglycerol lipase and clinical candidate for treatment of neurological disorders. J. Med. Chem. 2018 61 20 9062 9084 10.1021/acs.jmedchem.8b00951 30067909
    [Google Scholar]
  76. Jiang M. van der Stelt M. Activity-based protein profiling delivers selective drug candidate ABX-1431, a monoacylglycerol lipase inhibitor, to control lipid metabolism in neurological disorders. J. Med. Chem. 2018 61 20 9059 9061 10.1021/acs.jmedchem.8b01405 30354159
    [Google Scholar]
  77. Butler C.R. Beck E.M. Harris A. Huang Z. McAllister L.A. am Ende C.W. Fennell K. Foley T.L. Fonseca K. Hawrylik S.J. Johnson D.S. Knafels J.D. Mente S. Noell G.S. Pandit J. Phillips T.B. Piro J.R. Rogers B.N. Samad T.A. Wang J. Wan S. Brodney M.A. Azetidine and piperidine carbamates as efficient, covalent inhibitors of monoacylglycerol lipase. J. Med. Chem. 2017 60 23 9860 9873 10.1021/acs.jmedchem.7b01531 29148769
    [Google Scholar]
  78. Johansson A. Löfberg C. Antonsson M. von Unge S. Hayes M.A. Judkins R. Ploj K. Benthem L. Lindén D. Brodin P. Wennerberg M. Fredenwall M. Li L. Persson J. Bergman R. Pettersen A. Gennemark P. Hogner A. Discovery of (3-(4-(2-Oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone (AZD1979), a Melanin Concentrating Hormone Receptor 1 (MCHr1) Antagonist with Favorable Physicochemical Properties. J. Med. Chem. 2016 59 6 2497 2511 10.1021/acs.jmedchem.5b01654 26741166
    [Google Scholar]
  79. Cheng R. Mori W. Ma L. Alhouayek M. Hatori A. Zhang Y. Ogasawara D. Yuan G. Chen Z. Zhang X. Shi H. Yamasaki T. Xie L. Kumata K. Fujinaga M. Nagai Y. Minamimoto T. Svensson M. Wang L. Du Y. Ondrechen M.J. Vasdev N. Cravatt B.F. Fowler C. Zhang M.R. Liang S.H. In vitro and in vivo evaluation of 11C-labeled azetidinecarboxylates for imaging monoacylglycerol lipase by PET imaging studies. J. Med. Chem. 2018 61 6 2278 2291 10.1021/acs.jmedchem.7b01400 29481079
    [Google Scholar]
  80. Zhang L. Butler C.R. Maresca K.P. Takano A. Nag S. Jia Z. Arakawa R. Piro J.R. Samad T. Smith D.L. Nason D.M. O’Neil S. McAllister L. Schildknegt K. Trapa P. McCarthy T.J. Villalobos A. Halldin C. Identification and development of an irreversible monoacylglycerol lipase (MAGL) positron emission tomography (PET) radioligand with high specificity. J. Med. Chem. 2019 62 18 8532 8543 10.1021/acs.jmedchem.9b00847 31483137
    [Google Scholar]
  81. Blankman J.L. Simon G.M. Cravatt B.F. A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem. Biol. 2007 14 12 1347 1356 10.1016/j.chembiol.2007.11.006 18096503
    [Google Scholar]
  82. Savinainen J.R. Saario S.M. Laitinen J.T. The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2‐arachidonoylglycerol signalling through cannabinoid receptors. Acta Physiol. (Oxf.) 2012 204 2 267 276 10.1111/j.1748‑1716.2011.02280.x 21418147
    [Google Scholar]
  83. Li F. Fei X. Xu J. Ji C. An unannotated α/β hydrolase superfamily member, ABHD6 differentially expressed among cancer cell lines. Mol. Biol. Rep. 2009 36 4 691 696 10.1007/s11033‑008‑9230‑7 18360779
    [Google Scholar]
  84. Zhao S. Mugabo Y. Iglesias J. Xie L. Delghingaro-Augusto V. Lussier R. Peyot M.L. Joly E. Taïb B. Davis M.A. Brown J.M. Abousalham A. Gaisano H. Madiraju S.R.M. Prentki M. α/β-Hydrolase domain-6-accessible monoacylglycerol controls glucose-stimulated insulin secretion. Cell Metab. 2014 19 6 993 1007 10.1016/j.cmet.2014.04.003 24814481
    [Google Scholar]
  85. Zhao S. Mugabo Y. Ballentine G. Attane C. Iglesias J. Poursharifi P. Zhang D. Nguyen T.A. Erb H. Prentki R. Peyot M.L. Joly E. Tobin S. Fulton S. Brown J.M. Madiraju S.R.M. Prentki M. α/β-Hydrolase domain 6 deletion induces adipose browning and prevents obesity and type 2 diabetes. Cell Rep. 2016 14 12 2872 2888 10.1016/j.celrep.2016.02.076 26997277
    [Google Scholar]
  86. Zhao S. Poursharifi P. Mugabo Y. Levens E.J. Vivot K. Attane C. Iglesias J. Peyot M. Joly E. Madiraju S.R.M. Prentki M. α/β-Hydrolase domain-6 and saturated long chain monoacylglycerol regulate insulin secretion promoted by both fuel and non-fuel stimuli. Mol. Metab. 2015 4 12 940 950 10.1016/j.molmet.2015.09.012 26909310
    [Google Scholar]
  87. Alhouayek M. Masquelier J. Cani P.D. Lambert D.M. Muccioli G.G. Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol ester in the control of macrophage activation and inflammation by ABHD6. Proc. Natl. Acad. Sci. USA 2013 110 43 17558 17563 10.1073/pnas.1314017110 24101490
    [Google Scholar]
  88. Li W. Blankman J.L. Cravatt B.F. A functional proteomic strategy to discover inhibitors for uncharacterized hydrolases. J. Am. Chem. Soc. 2007 129 31 9594 9595 10.1021/ja073650c 17629278
    [Google Scholar]
  89. Bachovchin D.A. Ji T. Li W. Simon G.M. Blankman J.L. Adibekian A. Hoover H. Niessen S. Cravatt B.F. Superfamily-wide portrait of serine hydrolase inhibition achieved by library-versus-library screening. Proc. Natl. Acad. Sci. USA 2010 107 49 20941 20946 10.1073/pnas.1011663107 21084632
    [Google Scholar]
  90. Patel J.Z. Nevalainen T.J. Savinainen J.R. Adams Y. Laitinen T. Runyon R.S. Vaara M. Ahenkorah S. Kaczor A.A. Navia-Paldanius D. Gynther M. Aaltonen N. Joharapurkar A.A. Jain M.R. Haka A.S. Maxfield F.R. Laitinen J.T. Parkkari T. Optimization of 1,2,5-thiadiazole carbamates as potent and selective ABHD6 inhibitors. ChemMedChem 2015 10 2 253 265 10.1002/cmdc.201402453 25504894
    [Google Scholar]
  91. Long J.Z. Nomura D.K. Vann R.E. Walentiny D.M. Booker L. Jin X. Burston J.J. Sim-Selley L.J. Lichtman A.H. Wiley J.L. Cravatt B.F. Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo. Proc. Natl. Acad. Sci. USA 2009 106 48 20270 20275 10.1073/pnas.0909411106 19918051
    [Google Scholar]
  92. Ahn K. Johnson D.S. Fitzgerald L.R. Liimatta M. Arendse A. Stevenson T. Lund E.T. Nugent R.A. Nomanbhoy T.K. Alexander J.P. Cravatt B.F. Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity. Biochemistry 2007 46 45 13019 13030 10.1021/bi701378g 17949010
    [Google Scholar]
  93. Ahn K. Johnson D.S. Mileni M. Beidler D. Long J.Z. McKinney M.K. Weerapana E. Sadagopan N. Liimatta M. Smith S.E. Lazerwith S. Stiff C. Kamtekar S. Bhattacharya K. Zhang Y. Swaney S. Van Becelaere K. Stevens R.C. Cravatt B.F. Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem. Biol. 2009 16 4 411 420 10.1016/j.chembiol.2009.02.013 19389627
    [Google Scholar]
  94. Anderson W.B. Gould M.J. Torres R.D. Mitchell V.A. Vaughan C.W. Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine inflammatory pain model. Neuropharmacology 2014 81 224 230 10.1016/j.neuropharm.2013.12.018 24384256
    [Google Scholar]
  95. Adamson Barnes N.S. Mitchell V.A. Kazantzis N.P. Vaughan C.W. Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine neuropathic pain model. Br. J. Pharmacol. 2016 173 1 77 87 10.1111/bph.13337 26398331
    [Google Scholar]
  96. Brindisi M. Brogi S. Maramai S. Grillo A. Borrelli G. Butini S. Novellino E. Allarà M. Ligresti A. Campiani G. Di Marzo V. Gemma S. Harnessing the pyrroloquinoxaline scaffold for FAAH and MAGL interaction: Definition of the structural determinants for enzyme inhibition. RSC Advances 2016 6 69 64651 64664 10.1039/C6RA12524G
    [Google Scholar]
  97. Saario S.M. Poso A. Juvonen R.O. Järvinen T. Salo-Ahen O.M.H. Fatty acid amide hydrolase inhibitors from virtual screening of the endocannabinoid system. J. Med. Chem. 2006 49 15 4650 4656 10.1021/jm060394q 16854070
    [Google Scholar]
  98. Seillier A. Dominguez Aguilar D. Giuffrida A. The dual FAAH/MAGL inhibitor JZL195 has enhanced effects on endocannabinoid transmission and motor behavior in rats as compared to those of the MAGL inhibitor JZL184. Pharmacol. Biochem. Behav. 2014 124 153 159 10.1016/j.pbb.2014.05.022 24911644
    [Google Scholar]
  99. Niphakis M.J. Johnson D.S. Ballard T.E. Stiff C. Cravatt B.F. O-hydroxyacetamide carbamates as a highly potent and selective class of endocannabinoid hydrolase inhibitors. ACS Chem. Neurosci. 2012 3 5 418 426 10.1021/cn200089j 22860211
    [Google Scholar]
  100. Barth M. Rudolph S. Kampschulze J. Meyer zu Vilsendorf I. Hanekamp W. Mulac D. Langer K. Lehr M. Hexafluoroisopropyl carbamates as selective MAGL and dual MAGL/FAAH inhibitors: Biochemical and physicochemical properties. ChemMedChem 2022 17 9 e202100757 10.1002/cmdc.202100757 35072346
    [Google Scholar]
  101. Jaiswal S. Gupta G. Ayyannan S.R. Synthesis and evaluation of carbamate derivatives as fatty acid amide hydrolase and monoacylglycerol lipase inhibitors. Arch. Pharm. (Weinheim) 2022 355 11 2200081 10.1002/ardp.202200081 35924298
    [Google Scholar]
  102. Rampa A. Bartolini M. Bisi A. Belluti F. Gobbi S. Andrisano V. Ligresti A. Di Marzo V. The first dual ChE/FAAH inhibitors: New perspectives for Alzheimer’s disease? ACS Med. Chem. Lett. 2012 3 3 182 186 10.1021/ml200313p 24900454
    [Google Scholar]
  103. Montanari S. Scalvini L. Bartolini M. Belluti F. Gobbi S. Andrisano V. Ligresti A. Di Marzo V. Rivara S. Mor M. Bisi A. Rampa A. Fatty acid amide hydrolase (FAAH), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE): Networked targets for the development of carbamates as potential anti-Alzheimer’s disease agents. J. Med. Chem. 2016 59 13 6387 6406 10.1021/acs.jmedchem.6b00609 27309570
    [Google Scholar]
  104. Rudolph S. Dahlhaus H. Hanekamp W. Albers C. Barth M. Michels G. Friedrich D. Lehr M. Aryl N. -[ω-(6-fluoroindol-1-yl) alkyl] carbamates as inhibitors of fatty acid amide hydrolase, monoacylglycerol lipase, and butyrylcholinesterase: Structure–activity relationships and hydrolytic stability. ACS Omega 2021 6 20 13466 13483 10.1021/acsomega.1c01699 34056494
    [Google Scholar]
  105. Maleki M.F. Nadri H. Kianfar M. Edraki N. Eisvand F. Ghodsi R. Mohajeri S.A. Hadizadeh F. Design and synthesis of new carbamates as inhibitors for fatty acid amide hydrolase and cholinesterases: Molecular dynamic, in vitro and in vivo studies. Bioorg. Chem. 2021 109 104684 10.1016/j.bioorg.2021.104684 33607363
    [Google Scholar]
  106. Maione S. De Petrocellis L. de Novellis V. Moriello A.S. Petrosino S. Palazzo E. Rossi F.S. Woodward D.F. Di Marzo V. Analgesic actions of N ‐arachidonoyl‐serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid TRPV1 receptors. Br. J. Pharmacol. 2007 150 6 766 781 10.1038/sj.bjp.0707145 17279090
    [Google Scholar]
  107. Gharat L. Szallasi A. Medicinal chemistry of the vanilloid (Capsaicin) TRPV1 receptor: Current knowledge and future perspectives. Drug Dev. Res. 2007 68 8 477 497 10.1002/ddr.20218
    [Google Scholar]
  108. Morera E. De Petrocellis L. Morera L. Moriello A.S. Ligresti A. Nalli M. Woodward D.F. Di Marzo V. Ortar G. Synthesis and biological evaluation of piperazinyl carbamates and ureas as fatty acid amide hydrolase (FAAH) and transient receptor potential (TRP) channel dual ligands. Bioorg. Med. Chem. Lett. 2009 19 23 6806 6809 10.1016/j.bmcl.2009.09.033 19875281
    [Google Scholar]
  109. De Simone A. Ruda G.F. Albani C. Tarozzo G. Bandiera T. Piomelli D. Cavalli A. Bottegoni G. Applying a multitarget rational drug design strategy: The first set of modulators with potent and balanced activity toward dopamine D3 receptor and fatty acid amide hydrolase. Chem. Commun. (Camb.) 2014 50 38 4904 4907 10.1039/C4CC00967C 24691497
    [Google Scholar]
  110. Micoli A. De Simone A. Russo D. Ottonello G. Colombano G. Ruda G.F. Bandiera T. Cavalli A. Bottegoni G. Aryl and heteroaryl N -[4-[4-(2,3-substituted-phenyl)piperazine-1-yl]alkyl]carbamates with improved physico-chemical properties as dual modulators of dopamine D3 receptor and fatty acid amide hydrolase. MedChemComm 2016 7 3 537 541 10.1039/C5MD00590F
    [Google Scholar]
  111. De Simone A. Russo D. Ruda G.F. Micoli A. Ferraro M. Di Martino R.M.C. Ottonello G. Summa M. Armirotti A. Bandiera T. Cavalli A. Bottegoni G. Design, synthesis, structure–activity relationship studies, and three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling of a series of o-biphenyl carbamates as dual modulators of dopamine d3 receptor and fatty acid amide hydrolas. J. Med. Chem. 2017 60 6 2287 2304 10.1021/acs.jmedchem.6b01578 28182408
    [Google Scholar]
/content/journals/mrmc/10.2174/0113895575328120241107061303
Loading
Promising Inhibitors of Endocannabinoid Degrading Enzymes Sharing a Carbamate Scaffold
Bentham Science Publishers ; https://doi.org/10.2174/0113895575328120241107061303
/content/journals/mrmc/10.2174/0113895575328120241107061303
/content/journals/mrmc/10.2174/0113895575328120241107061303
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: fatty acid amide hydrolase ; Carbamate ; monoacylglycerol lipase ; endocannabinoid ; neurotherapeutic

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test