Discovery and development of endocannabinoid-hydrolyzing enzyme inhibitors

Current Topics in Medicinal Chemistry

Volumn 10, Issue 8, 2010, Pages 828-858

  Minkkilä, Anna ^a   Saario, Susanna M ^a,b   Nevalainen, Tapio ^a  

^a UNIVERSITY OF EASTERN FINLAND   (Finland)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

2 arachidonoylglycerol; Endocannabinoids; Fatty acid amide hydrolase; Monoacylglycerol lipase; Monoglyceride lipase; N arachidonoylethanolamine

Indexed keywords

1 [[6 (3 METHOXYESTRA 1,3,5(10) TRIEN 17BETA YL)AMINO]HEXYL] 1H PYRROLE 2,5 DIONE; 1,6 HEXAMETHYLENEDICARBAMIC ACID BIS(CYCLOHEXANONE OXIME) ESTER; 2 ARACHIDONOYLGLYCEROL; 7 PHENYL 1 [5 (2 PYRIDINYL) 2 OXAZOLYL] 1 HEPTANONE; AA 5 HT; ACYLGLYCEROL LIPASE; ANANDAMIDE; BENZYLSULFONYL FLUORIDE; BMS 1; BORONIC ACID DERIVATIVE; BROMOENOL LACTONE; CANNABINOID 2 RECEPTOR; CANNABIS; CARBAMIC ACID DERIVATIVE; CAY 10499; CAY10401; CAY10435; CYCLOHEXYLCARBAMIC ACID 3' CARBAMOYLBIPHENYL 3 YL ESTER; ENDOCANNABINOID; FATTY ACID AMIDASE INHIBITOR; HYDANTOIN DERIVATIVE; HYDROLASE INHIBITOR; JN 1661010; JP83; JZL184; JZL195; LY 2183240; N (4 HYDROXYPHENYL)ARACHIDONAMIDE; NETOGLITAZONE; OL 92; OMDM169; ORGANOPHOSPHATE; PARAOXON; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PF 3845; PF 4457845; PF 750; RIVASTIGMINE; SA 47; SSR 411298; TETRAHYDROCANNABINOL; THIOHYDANTOIN DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; URB524; URB532; URB602; URB880; UREA DERIVATIVE; VANILLOID RECEPTOR 1; VER 156084;

ALZHEIMER DISEASE; ANXIETY; ARTICLE; ATHEROSCLEROSIS; BIOSYNTHESIS; CALCIUM CELL LEVEL; CLINICAL TRIAL; DEMYELINATION; DEPRESSION; ENZYMATIC DEGRADATION; HUMAN; IN VIVO STUDY; INFERTILITY; INSULIN RESISTANCE; MENTAL DISEASE; NEOPLASM; NONHUMAN; PAIN; PROTEIN TARGETING;

AMIDOHYDROLASES; ARACHIDONIC ACIDS; ENDOCANNABINOIDS; ENZYME INHIBITORS; GLYCERIDES; HUMANS; MONOACYLGLYCEROL LIPASES; NERVOUS SYSTEM DISEASES; TETRAHYDROCANNABINOL;

EID: 77954379126     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802610791164238     Document Type: Article

References (204)

1. Gaoni, Y.; Mechoulam, R. Isolation, structure, and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc., 1964, 86, 1646-1647.
2. Devane, W.; Dysarz, F. 3.; Johnson, M.; Melvin, L.; Howlett, A. Determination and characterization of a cannabinoid receptor in rat brain. Mol. Pharmacol., 1988, 34, 605-613.
3. Matsuda, L. A.; Lolait, S. J.; Brownstein, M. J.; Young, A. C.; Bonner, T. I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature, 1990, 346, 561-564.
4. Munro, S.; Thomas, K. L.; Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature, 1993, 365, 61-65.
5. Pertwee, R. G. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol. Ther., 1997, 74, 129-180.
6. Di Marzo, V.; Bifulco, M.; De Petrocellis, L. The endocannabinoid system and its therapeutic exploitation. Nat. Rev. Drug Discov., 2004, 3, 771-784.
7. Fernández-Ruiz, J.; Romero, J.; Velasco, G.; Tolón, R. M.; Ramos, J. A.; Guzmán, M. Cannabinoid CB2 receptor: a new target for controlling neural cell survival? Trends Pharmacol. Sci., 2007, 28, 39-45.
8. Devane, W. A.; Hanus, L.; Breuer, A.; Pertwee, R. G.; Stevenson, L. A.; Griffin, G.; Gibson, D.; Mandelbaum, A.; Etinger, A.; Mechoulam, R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 1992, 258, 1946-1949.
9. Mechoulam, R.; Ben-Shabat, S.; Hanus, L.; Ligumsky, M.; Kaminski, N. E.; Schatz, A. R.; Gopher, A.; Almog, S.; Martin, B. R.; Compton, D. R. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol., 1995, 50, 83-90.
10. Sugiura, T.; Kondo, S.; Sukagawa, A.; Nakane, S.; Shinoda, A.; Itoh, K.; Yamashita, A.; Waku, K. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem. Biophys. Res. Commun., 1995, 215, 89-97.
11. Stella, N.; Schweitzer, P.; Piomelli, D. A second endogenous cannabinoid that modulates long-term potentiation. Nature, 1997, 388, 773-778.
12. Sugiura, T.; Kodaka, T.; Nakane, S.; Miyashita, T.; Kondo, S.; Suhara, Y.; Takayama, H.; Waku, K.; Seki, C.; Baba, N.; Ishima, Y. Evidence that the cannabinoid CB1 receptor Is a 2- arachidonoylglycerol receptor. J. Biol. Chem., 1999, 274, 2794-2801.
13. Gonsiorek, W.; Lunn, C.; Fan, X.; Narula, S.; Lundell, D.; Hipkin, R. W. Endocannabinoid 2-arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor: antagonism by anandamide. Mol. Pharmacol., 2000, 57, 1045-1050.
14. Sugiura, T.; Kondo, S.; Kishimoto, S.; Miyashita, T.; Nakane, S.; Kodaka, T.; Suhara, Y.; Takayama, H.; Waku, K. Evidence That 2- Arachidonoylglycerol but Not N-palmitoylethanolamine or anandamide Is the physiological Ligand for the cannabinoid CB2 receptor. J. Biol. Chem., 2000, 275, 605-612.
15. Savinainen, J. R.; Järvinen, T.; Laine, K.; Laitinen, J. T. Despite substantial degradation, 2-arachidonoylglycerol is a potent full efficacy agonist mediating CB1 receptor-dependent G-protein activation in rat cerebellar membranes. Br. J. Pharmacol., 2001, 134, 664-672.
16. Sugiura, T.; Kondo, S.; Kodaka, T.; Tonegawa, T.; Nakane, S.; Yamashita, A.; Ishima, Y.; Waku, K. Enzymatic synthesis of oleamide (cis-9,10-octadecenoamide), an endogenous sleepinducing lipid, by rat brain microsomes. IUBMB Life, 1996, 40, 931-938.
17. Leggett, J. D.; Aspley, S.; Beckett, S. R. G.; D'Antona, A. M.; Kendall, D. A.; Kendall, D. A. Oleamide is a selective endogenous agonist of rat and human CB1 cannabinoid receptors. Br. J. Pharmacol., 2004, 141, 253-262.
18. Sheskin, T.; Hanus, L.; Slager, J.; Vogel, Z.; Mechoulam, R. Structural requirements for binding of anandamide-type compounds to the brain cannabinoid receptor. J. Med. Chem., 1997, 40, 659-667.
19. Vandevoorde, S.; Jonsson, K.; Fowler, C. J.; Lambert, D. M. Modifications of the ethanolamine head in N-palmitoylethanolamine: synthesis and evaluation of new agents interfering with the metabolism of anandamide. J. Med. Chem., 2003, 46, 1440-1448.
20. Lin, S.; Khanolkar, A. D.; Fan, P.; Goutopoulos, A.; Qin, C.; Papahadjis, D.; Makriyannis, A. Novel analogues of arachidonylethanolamide (anandamide): affinities for the CB1 and CB2 cannabinoid receptors and metabolic stability. J. Med. Chem., 1998, 41, 5353-5361.
21. Sipe, J. C.; Arbour, N.; Gerber, A.; Beutler, E. Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism: possible risk for autoimmune disorders. J. Leukoc. Biol., 2005, 78, 231-238.
22. Bisogno, T.; Melck, D.; Bobrov, M. Y.; Gretskaya, N. M.; Bezuglov, V. V.; De Petrocellis, L.; Di Marzo, V. ]N-acyldopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo. Biochem. J., 2000, 351, 817-824.
23. Hanus, L.; Gopher, A.; Almog, S.; Mechoulam, R. Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor. J. Med. Chem., 1993, 36, 3032-3034.
24. Milman, G.; Maor, Y.; Abu-Lafi, S.; Horowitz, M.; Gallily, R.; Batkai, S.; Mo, F.; Offertaler, L.; Pacher, P.; Kunos, G.; Mechoulam, R. N-arachidonoyl l-serine, an endocannabinoid-like brain constituent with vasodilatory properties. Proc. Natl. Acad. Sci. USA, 2006, 103, 2428-2433.
25. Hanuš, L.; Abu-Lafi, S.; Fride, E.; Breuer, A.; Vogel, Z.; Shalev, D. E.; Kustanovich, I.; Mechoulam, R. 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc. Natl. Acad. Sci. USA, 2001, 98, 3662-3665.
26. Porter, A. C.; Sauer, J.; Knierman, M. D.; Becker, G. W.; Berna, M. J.; Bao, J.; Nomikos, G. G.; Carter, P.; Bymaster, F. P.; Leese, A. B.; Felder, C. C. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J. Pharmacol. Exp. Ther., 2002, 301, 1020-1024.
27. Alexander, S. P. H.; Kendall, D. A. The complications of promiscuity: endocannabinoid action and metabolism. Br. J. Pharmacol., 2007, 152, 602-623.
28. Piomelli, D. The molecular logic of endocannabinoid signalling. Nat. Rev. Neurosci., 2003, 4, 873-884.
29. Di Marzo, V. Endocannabinoids: synthesis and degradation. Rev. Physiol. Biochem. Pharmacol., 2008, 160, 1-24.
30. Ahn, K.; McKinney, M. K.; Cravatt, B. F. Enzymatic Pathways That Regulate endocannabinoid signaling in the nervous system. Chem. Rev., 2008, 108, 1687-1707.
31. Liu, J.; Wang, L.; Harvey-White, J.; Huang, B. X.; Kim, H.; Luquet, S.; Palmiter, R. D.; Krystal, G.; Rai, R.; Mahadevan, A.; Razdan, R. K.; Kunos, G. Multiple pathways involved in the biosynthesis of anandamide. Neuropharmacology, 2008, 54, 1-7.
32. [32] Okamoto, Y.; Tsuboi, K.; Ueda, N. Enzymatic formation of anandamide. In: Vitamins & Hormones; Gerald Litwack, Ed.; Chap. 1, Academic Press: 2009, Vol. 81, pp. 1-24.
33. Di Marzo, V.; Fontana, A.; Cadas, H.; Schinelli, S.; Cimino, G.; Schwartz, J.; Piomelli, D. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature, 1994, 372, 686-691.
34. Cadas, H.; di Tomaso, E.; Piomelli, D. Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in Rat Brain. J. Neurosci., 1997, 17, 1226-1242.
35. Leung, D.; Saghatelian, A.; Simon, G. M.; Cravatt, B. F. Inactivation of N-acyl phosphatidylethanolamine phospholipase D reveals multiple mechanisms for the biosynthesis of endocannabinoids. Biochemistry, (N. Y.) 2006, 45, 4720-4726.
36. Simon, G. M.; Cravatt, B. F. Anandamide biosynthesis catalyzed by the phosphodiesterase GDE1 and detection of glycerophospho- N-acyl ethanolamine precursors in mouse brain. J. Biol. Chem., 2008, 283, 9341-9349.
37. Liu, J.; Wang, L.; Harvey-White, J.; Osei-Hyiaman, D.; Razdan, R.; Gong, Q.; Chan, A. C.; Zhou, Z.; Huang, B. X.; Kim, H.; Kunos, G. A biosynthetic pathway for anandamide. Proc. Natl. Acad. Sci. USA, 2006, 103, 13345-13350.
38. Bisogno, T.; Howell, F.; Williams, G.; Minassi, A.; Cascio, M. G.; Ligresti, A.; Matias, I.; Schiano-Moriello, A.; Paul, P.; Williams, E.; Gangadharan, U.; Hobbs, C.; Di Marzo, V.; Doherty, P. Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J. Cell Biol., 2003, 163, 463-468.
39. Di Marzo, V.; Petrosino, S. Endocannabinoids and the regulation of their levels in health and disease. Curr. Opin. Lipidol., 2007, 18, 129-140.
40. Hashimotodani, Y.; Ohno-Shosaku, T.; Kano, M. Ca2+-assisted receptor-driven endocannabinoid release: mechanisms that associate presynaptic and postsynaptic activities. Curr. Opin. Neurobiol., 2007, 17, 360-365.
41. Di Marzo, V. Targeting the endocannabinoid system: to enhance or reduce? Nat. Rev. Drug Discov., 2008, 7, 438-455.
42. Kaczocha, M.; Glaser, S. T.; Deutsch, D. G. Identification of intracellular carriers for the endocannabinoid anandamide. Proc. Natl. Acad. Sci. USA, 2009, 106, 6375-6380.
43. Buckley, N. E.; McCoy, K. L.; Mezey, É.; Bonner, T.; Zimmer, A.; Felder, C. C.; Glass, M.; Zimmer, A. Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB2 receptor. Eur. J. Pharmacol., 2000, 396, 141-149.
44. Cravatt, B. F.; Giang, D. K.; Mayfield, S. P.; Boger, D. L.; Lerner, R. A.; Gilula, N. B. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature, 1996, 384, 83-87.
45. Dinh, T. P.; Carpenter, D.; Leslie, F. M.; Freund, T. F.; Katona, I.; Sensi, S. L.; Kathuria, S.; Piomelli, D. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc. Natl. Acad. Sci. USA, 2002, 99, 10819-10824.
46. Wei, B. Q.; Mikkelsen, T. S.; McKinney, M. K.; Lander, E. S.; Cravatt, B. F. A Second fatty acid amide hydrolase with variable distribution among placental mammals. J. Biol. Chem., 2006, 281, 36569-36578.
47. Tsuboi, K.; Sun, Y.; Okamoto, Y.; Araki, N.; Tonai, T.; Ueda, N. Molecular characterization of N-acylethanolamine-hydrolyzing acid amidase, a novel member of the choloylglycine hydrolase family with structural and functional similarity to acid ceramidase. J. Biol. Chem., 2005, 280, 11082-11092.
48. Goparaju, S. K.; Ueda, N.; Yamaguchi, H.; Yamamoto, S. Anandamide amidohydrolase reacting with 2-arachidonoylglycerol, another cannabinoid receptor ligand. FEBS Lett., 1998, 422, 69-73.
49. van Tienhoven, M.; Atkins, J.; Li, Y.; Glynn, P. Human neuropathy target esterase catalyzes hydrolysis of membrane lipids. J. Biol. Chem., 2002, 277, 20942-20948.
50. 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, 1347-1356.
51. Yu, M.; Ives, D.; Ramesha, C. S. Synthesis of prostaglandin E2 ethanolamide from Anandamide by cyclooxygenase-2. J. Biol. Chem., 1997, 272, 21181-21186.
52. Rouzer, C. A.; Marnett, L. J. Non-redundant functions of cyclooxygenases: oxygenation of endocannabinoids. J. Biol. Chem., 2008, 283, 8065-8069.
53. Edgemond, W. S.; Hillard, C. J.; Falck, J. R.; Kearn, C. S.; Campbell, W. B. Human platelets and polymorphonuclear leukocytes synthesize oxygenated derivatives of arachidonylethanolamide (Anandamide): their affinities for cannabinoid receptors and pathways of inactivation. Mol. Pharmacol., 1998, 54, 180-188.
54. Moody, J. S.; Kozak, K. R.; Ji, C.; Marnett, L. J. Selective oxygenation of the endocannabinoid 2-arachidonylglycerol by leukocyte-Type 12-lipoxygenase. Biochemistry, (N. Y.) 2001, 40, 861-866.
55. Kozak, K. R.; Gupta, R. A.; Moody, J. S.; Ji, C.; Boeglin, W. E.; DuBois, R. N.; Brash, A. R.; Marnett, L. J. 15-lipoxygenase metabolism of 2-arachidonylglycerol. generation of a peroxisome proliferator-activated receptor alpha agonist. J. Biol. Chem., 2002, 277, 23278-23286.
56. Starowicz, K.; Nigam, S.; Di Marzo, V. Biochemistry and pharmacology of endovanilloids. Pharmacol. Ther., 2007, 114, 13-33.
57. O'Sullivan, S. E. Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors. Br. J. Pharmacol., 2007, 152, 576-582.
58. Oz, M. Receptor-independent effects of endocannabinoids on ion channels. Curr. Pharm. Des., 2006, 12, 227-239.
59. Caterina, M. J.; Julius, D. The vanilloid receptor: A molecular gateway to the pain pathway. Annu. Rev. Neurosci., 2001, 24, 487-517.
60. Berger, J.; Moller, D. E. The mechanisms of action of PPARs. Annu. Rev. Med. 2002, 53, 409-435.
61. Ryberg, E.; Larsson, N.; Sjogren, S.; Hjorth, S.; Hermansson, N. O.; Leonova, J.; Elebring, T.; Nilsson, K.; Drmota, T.; Greasley, P. J. The orphan receptor GPR55 is a novel cannabinoid receptor. Br. J. Pharmacol., 2007, 152, 1092-1101.
62. Lambert, D. M.; Fowler, C. J. The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications. J. Med. Chem., 2005, 48, 5059-5087.
63. Saario, S. M.; Laitinen, J. T. Therapeutic potential of endocannabinoid- hydrolysing enzyme inhibitors. Basic Clin. Pharmacol. Toxicol., 2007, 101, 287-293.
64. Hanuš, L. Pharmacological and therapeutic secrets of plant and brain (endo)cannabinoids. Med. Res. Rev., 2009, 29, 213-271.
65. Vandevoorde, S. Overview of the chemical families of fatty acid amide hydrolase and monoacylglycerol lipase inhibitors. Curr. Top. Med. Chem., 2008, 8, 247-267.
66. Viso, A.; Cisneros, J. A.; Ortega-Gutierrez, S. The medicinal chemistry of agents targeting monoacylglycerol lipase. Curr. Top. Med. Chem., 2008, 8, 231-246.
67. Seierstad, M.; Breitenbucher, J. G. Discovery and development of fatty acid amide hydrolase (FAAH) inhibitors. J. Med. Chem., 2008, 51, 7327-7343.
68. Giang, D. K.; Cravatt, B. F. Molecular characterization of human and mouse fatty acid amide hydrolases. Proc. Natl. Acad. Sci. USA, 1997, 94, 2238-2242.
69. Saghatelian, A.; Trauger, S. A.; Want, E. J.; Hawkins, E. G.; Siuzdak, G.; Cravatt, B. F. Assignment of endogenous substrates to enzymes by global metabolite profiling. Biochemistry (NY), 2004, 43, 14332-14339.
70. Cravatt, B.; Prospero-Garcia, O.; Siuzdak, G.; Gilula, N.; Henriksen, S.; Boger, D.; Lerner, R. Chemical characterization of a family of brain lipids that induce sleep. Science, 1995, 268, 1506-1509.
71. Patricelli, M. P.; Cravatt, B. F. Fatty acid amide hydrolase competitively degrades bioactive amides and esters through a nonconventional catalytic mechanism. Biochemistry (NY), 1999, 38, 14125-14130.
72. Patricelli, M. P.; Lovato, M. A.; Cravatt, B. F. Chemical and mutagenic investigations of fatty acid amide hydrolase: evidence for a family of serine hydrolases with distinct catalytic properties. Biochemistry (NY), 1999, 38, 9804-9812.
73. Bracey, M. H.; Hanson, M. A.; Masuda, K. R.; Stevens, R. C.; Cravatt, B. F. Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling. Science, 2002, 298, 1793-1796.
74. Mileni, M.; Johnson, D. S.; Wang, Z.; Everdeen, D. S.; Liimatta, M.; Pabst, B.; Bhattacharya, K.; Nugent, R. A.; Kamtekar, S.; Cravatt, B. F.; Ahn, K.; Stevens, R. C. Structure-guided inhibitor design for human FAAH by interspecies active site conversion. Proc. Natl. Acad. Sci. USA, 2008, 105, 12820-12824.
75. Deutsch, D. G.; Chin, S. A. Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist. Biochem. Pharmacol., 1993, 46, 791-796.
76. Deutsch, D. G.; Lin, S.; Hill, W. A. G.; Morse, K. L.; Salehani, D.; Arreaza, G.; Omeir, R. L.; Makriyannis, A. Fatty acid sulfonyl fluorides inhibit anandamide metabolism and bind to the cannabinoid receptor. Biochem. Biophys. Res. Commun., 1997, 231, 217-221.
77. Deutsch, D. G.; Omeir, R.; Arreaza, G.; Salehani, D.; Prestwich, G. D.; Huang, Z.; Howlett, A. Methyl arachidonyl fluorophosphonate: a potent irreversible inhibitor of anandamide amidase. Biochem. Pharmacol., 1997, 53, 255-260.
78. Segall, Y.; Quistad, G. B.; Nomura, D. K.; Casida, J. E. Arachidonylsulfonyl derivatives as cannabinoid CB1 receptor and fatty acid amide hydrolase inhibitors. Bioorg. Med. Chem. Lett., 2003, 13, 3301-3303.
79. De Petrocellis, L.; Melck, D.; Ueda, N.; Maurelli, S.; Kurahashi, Y.; Yamamoto, S.; Marino, G.; Di Marzo, V. Novel inhibitors of brain, neuronal, and basophilic anandamide amidohydrolase. Biochem. Biophys. Res. Commun., 1997, 231, 82-88.
80. Patricelli, M. P.; Patterson, J. E.; Boger, D. L.; Cravatt, B. F. An endogenous sleep-inducing compound is a novel competitive inhibitor of fatty acid amide hydrolase. Bioorg. Med. Chem. Lett., 1998, 8, 613-618.
81. Koutek, B.; Prestwich, G. D.; Howlett, A. C.; Chin, S. A.; Salehani, D.; Akhavan, N.; Deutsch, D. G. Inhibitors of arachidonoyl ethanolamide hydrolysis. J. Biol. Chem., 1994, 269, 22937-22940.
82. Beltramo, M.; di Tomaso, E.; Piomelli, D. Inhibition of anandamide hydrolysis in rat brain tissue by (E)-6-(bromomethylene) tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one. FEBS Lett., 1997, 403, 263-267.
83. Saario, S. M.; Savinainen, J. R.; Laitinen, J. T.; Järvinen, T.; Niemi, R. Monoglyceride lipase-like enzymatic activity is responsible for hydrolysis of 2-arachidonoylglycerol in rat cerebellar membranes. Biochem. Pharmacol., 2004, 67, 1381-1387.
84. Maryanoff, B. E.; Costanzo, M. J. Inhibitors of proteases and amide hydrolases that employ an α-ketoheterocycle as a key enabling functionality. Bioorg. Med. Chem., 2008, 16, 1562-1595.
85. 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, 5044-5049.
86. Boger, D. L.; Miyauchi, H.; Hedrick, M. P. α-Keto heterocycle inhibitors of fatty acid amide hydrolase: carbonyl group modification and α-substitution. Bioorg. Med. Chem. Lett., 2001, 11, 1517-1520.
87. Leung, D.; Du, W.; Hardouin, C.; Cheng, H.; Hwang, I.; Cravatt, B. F.; Boger, D. L. Discovery of an exceptionally potent and selective class of fatty acid amide hydrolase inhibitors enlisting proteome-wide selectivity screening: concurrent optimization of enzyme inhibitor potency and selectivity. Bioorg. Med. Chem. Lett., 2005, 15, 1423-1428.
88. Boger, D. L.; Miyauchi, H.; Du, W.; Hardouin, C.; Fecik, R. A.; Cheng, H.; Hwang, I.; Hedrick, M. P.; Leung, D.; Acevedo, O.; Guimaraes, C. R. W.; Jorgensen, W. L.; Cravatt, B. F.Discovery of a potent, selective, and efficacious class of reversible alphaketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics. J. Med. Chem., 2005, 48, 1849-1856.
89. Romero, F. A.; Hwang, I.; Boger, D. L. Delineation of a fundamental alpha-ketoheterocycle substituent effect for use in the design of enzyme inhibitors. J. Am. Chem. Soc., 2006, 128, 14004-14005.
90. Romero, F. A.; Du, W.; Hwang, I.; Rayl, T. J.; Kimball, F. S.; Leung, D.; Hoover, H. S.; Apodaca, R. L.; Breitenbucher, J. G.; Cravatt, B. F.; Boger, D. L. Potent and selective alphaketoheterocycle- based inhibitors of the anandamide and oleamide catabolizing enzyme, fatty acid amide hydrolase. J. Med. Chem., 2007, 50, 1058-1068.
91. Hardouin, C.; Kelso, M. J.; Romero, F. A.; Rayl, T. J.; Leung, D.; Hwang, I.; Cravatt, B. F.; Boger, D. L. Structure activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase. J. Med. Chem., 2007, 50, 3359-3368.
92. DeMartino, J. K.; Garfunkle, J.; Hochstatter, D. G.; Cravatt, B. F.; Boger, D. L. Exploration of a fundamental substituent effect of α-ketoheterocycle enzyme inhibitors: potent and selective inhibitors of fatty acid amide hydrolase. Bioorg. Med. Chem. Lett., 2008, 18, 5842-5846.
93. Garfunkle, J.; Ezzili, C.; Rayl, T. J.; Hochstatter, D. G.; Hwang, I.; Boger, D. L. Optimization of the central heterocycle of alphaketoheterocycle inhibitors of fatty acid amide hydrolase. J. Med. Chem., 2008, 51, 4392-4403.
94. Lichtman, A. H.; Leung, D.; Shelton, C. C.; Saghatelian, A.; Hardouin, C.; Boger, D. L.; Cravatt, B. F. Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivity. J. Pharmacol. Exp. Ther., 2004, 311, 441-448.
95. Zhang, D.; Saraf, A.; Kolasa, T.; Bhatia, P.; Zheng, G. Z.; Patel, M.; Lannoye, G. S.; Richardson, P.; Stewart, A.; Rogers, J. C.; Brioni, J. D.; Surowy, C. S. Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets. Neuropharmacology, 2007, 52, 1095-1105.
96. Leung, D.; Hardouin, C.; Boger, D. L.; Cravatt, B. F. Discovering potent and selective reversible inhibitors of enzymes in complex proteomes. Nat. Biotechnol., 2003, 21, 687-691.
97. Sogorb, M. A.; Vilanova, E. Enzymes involved in the detoxification of organophosphorus, carbamate and pyrethroid insecticides through hydrolysis. Toxicol. Lett., 2002, 128, 215-228.
98. Winblad, B.; Grossberg, G.; Frolich, L.; Farlow, M.; Zechner, S.; Nagel, J.; Lane, R. IDEAL: A 6-month, double-blind, placebocontrolled study of the first skin patch for Alzheimer disease. Neurology, 2007, 69, S14-22.
99. Kathuria, S.; Gaetani, S.; Fegley, D.; Valino, F.; Duranti, A.; Tontini, A.; Mor, M.; Tarzia, G.; Rana, G. L.; Calignano, A.; Giustino, A.; Tattoli, M.; Palmery, M.; Cuomo, V.; Piomelli, D. Modulation of anxiety through blockade of anandamide hydrolysis. Nat. Med., 2003, 9, 76-81.
100. 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, 2352-2360.
101. 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, 1179-1187.
102. 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, 1505-1513.
103. 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, 4998-5008.
104. 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, 3487-3498.
105. Abouabdellah, A.; Bas, M.; Dargazanli, G.; Hoornaert, C.; Li, A. T.; Medaisko, F. Derivatives of dioxane-2-alkyl carbamates, preparation thereof and application thereof in therapeutics. U.S. Patent 2005/0182130, 2005.
106. 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, 130-139.
107. 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, 3287-3291.
108. Myllymaki, M. J.; Saario, S. M.; Kataja, A. O.; Castillo-Melendez, J.; 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, 4236-4242.
109. Myllymäki, M.; Castillo-Melendez, J.; Koskinen, A. M. P.; Minkkilä, A.; Saario, S. M.; Nevalainen, T.; Järvinen, T.; Poso, A.; Salo-Ahen, O. Novel N-heterocyclic phenyl carbamates as novel FAAH-inhibitors. PCT Int. Appl. 2008129129 A1, 2008.
110. 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, 4179-4191.
111. Vacondio, F.; Silva, C.; Lodola, A.; Fioni, A.; Rivara, S.; Duranti, A.; Tontini, A.; Sanchini, S.; Clapper, J. R.; Piomelli, D.; Mor, M.; Tarzia, G. Structure-property relationships of a class of carbamatebased fatty acid amide hydrolase (FAAH) inhibitors: chemical and biological stability. ChemMedChem, 2009, 4, 1495-1504.
112. Minkkilä, A.; Myllymäki, M. J.; Saario, S. M.; Castillo-Melendez, J. A.; Koskinen, A. M. P.; Fowler, C. J.; Leppänen, J.; Nevalainen, T. The synthesis and biological evaluation of para-substituted phenolic N-alkyl carbamates as endocannabinoid hydrolyzing enzyme inhibitors. Eur. J. Med. Chem., 2009, 44, 2994-3008.
113. Alexander, J. P.; Cravatt, B. F. The putative endocannabinoid transport blocker LY2183240 is a potent inhibitor of FAAH and several other brain serine hydrolases. J. Am. Chem. Soc., 2006, 128, 9699-9704.
114. Moore, S. A.; Nomikos, G. G.; Dickason-Chesterfield, A. K.; Schober, D. A.; Schaus, J. M.; Ying, B.-P.; Xu, Y.-C.; Phebus, L.; Simmons, R. M. A.; Li, D.; Iyengar, S.; Felder, C. C. Identification of a high-affinity binding site involved in the transport of endocannabinoids. Proc. Natl. Acad. Sci. USA, 2005, 102, 17852-17857.
115. Ortar, G.; Cascio, M. G.; Moriello, A. S.; Camalli, M.; Morera, E.; Nalli, M.; Di Marzo, V. Carbamoyl tetrazoles as inhibitors of endocannabinoid inactivation: A critical revisitation. Eur. J. Med. Chem., 2008, 43, 62-72.
116. Even, L.; Hoornaert, C. Derivatives of triazolopyridine carboxamides, particularly (piperazin-1-yl)(1,2,3-triazolo[4,5- b]pyridine-1-yl)methanones, their preparation and use as selective monoacyl glycerol lipase (MGL) or mixed MGL and fatty acid amide hydrolase inhibitors. PCT Int. Appl., 2008145843, 2008.
117. Minkkilä, A.; Savinainen, J. R.; Käsnänen, H.; Xhaard, H.; Nevalainen, T.; Laitinen, J. T.; Poso, A.; Leppänen, J.; Saario, S. M. Screening of various hormone-sensitive lipase inhibitors as endocannabinoid-hydrolyzing enzyme inhibitors. ChemMedChem, 2009, 4, 1253-1259.
118. Lowe, D. B.; Magnuson, S.; Qi, N.; Campbell, A.; Cook, J.; Hong, Z.; Wang, M.; Rodriguez, M.; Achebe, F.; Kluender, H.; Wong, W. C.; Bullock, W. H.; Salhanick, A. I.; Witman-Jones, T.; Bowling, M. E.; Keiper, C.; Clairmont, K. B. In vitro SAR of (5-(2H)- isoxazolonyl) ureas, potent inhibitors of hormone-sensitive lipase. Bioorg. Med. Chem. Lett., 2004, 14, 3155-3159.
119. Ebdrup, S.; Sorensen, L. G.; Olsen, O. H.; Jacobsen, P. Synthesis and structure-activity relationship for a novel class of potent and selective carbamoyl-triazole based inhibitors of hormone sensitive lipase. J. Med. Chem., 2004, 47, 400-410.
120. 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 (NY), 2007, 46, 13019-13030.
121. Keith, J. M.; Apodaca, R.; Xiao, W.; Seierstad, M.; Pattabiraman, K.; Wu, J.; Webb, M.; Karbarz, M. J.; Brown, S.; Wilson, S.; Scott, B.; Tham, C.; Luo, L.; Palmer, J.; Wennerholm, M.; Chaplan, S.; Breitenbucher, J. G. Thiadiazolopiperazinyl ureas as inhibitors of fatty acid amide hydrolase. Bioorg. Med. Chem. Lett., 2008, 18, 4838-4843.
122. Johnson, D. S.; Ahn, K.; Kesten, S.; Lazerwith, S. E.; Song, Y.; Morris, M.; Fay, L.; Gregory, T.; Stiff, C.; Dunbar Jr., J. B.; Liimatta, M.; Beidler, D.; Smith, S.; Nomanbhoy, T. K.; Cravatt, B. F. Benzothiophene piperazine and piperidine urea inhibitors of fatty acid amide hydrolase (FAAH). Bioorg. Med. Chem. Lett., 2009, 19, 2865-2869.
123. 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, 411-420.
124. Hart, T.; Macias, A. T.; Benwell, K.; Brooks, T.; D'Alessandro, J.; Dokurno, P.; Francis, G.; Gibbons, B.; Haymes, T.; Kennett, G.; Lightowler, S.; Mansell, H.; Matassova, N.; Misra, A.; Padfield, A.; Parsons, R.; Pratt, R.; Robertson, A.; Walls, S.; Wong, M.; Roughley, S. Fatty acid amide hydrolase inhibitors. Surprising selectivity of chiral azetidine ureas. Bioorg. Med. Chem. Lett., 2009, 19, 4241-4244.
125. Quistad, G. B.; Sparks, S. E.; Casida, J. E. Fatty acid amide hydrolase inhibition by neurotoxic organophosphorus pesticides. Toxicol. Appl. Pharmacol., 2001, 173, 48-55.
126. Nomura, D. K.; Blankman, J. L.; Simon, G. M.; Fujioka, K.; Issa, R. S.; Ward, A. M.; Cravatt, B. F.; Casida, J. E. Activation of the endocannabinoid system by organophosphorus nerve agents. Nat. Chem. Biol., 2008, 4, 373-378.
127. Page, M. I.; Laws, A. P. The chemical reactivity of β-lactams, β-sultams and β-phospholactams. Tetrahedron, 2000, 56, 5631-5638.
128. Firestone, R. A.; Barker, P. L.; Pisano, J. M.; Ashe, B. M.; Dahlgren, M. E. Monocyclic β-lactam inhibitors of human leukocyte elastase. Tetrahedron, 1990, 46, 2255-2262.
129. Lu, W.; Kincaid, E.; Sun, Y.; Bauer, M. D. Kinetics of β-lactam interactions with penicillin-susceptible and -resistant penicillinbinding protein 2x proteins from streptococcus pneumoniae. J. Biol. Chem., 2001, 276, 31494-31501.
130. Urbach, A.; Muccioli, G. G.; Stern, E.; Lambert, D. M.; Marchandbrynaert, J. 3-alkenyl-2-azetidinones as fatty acid amide hydrolase inhibitors. Bioorg. Med. Chem. Lett., 2008, 18, 4163-4167.
131. Feledziak, M.; Michaux, C.; Urbach, A.; Labar, G.; Muccioli, G. G.; Lambert, D. M.; Marchand-Brynaert, J. beta-Lactams derived from a carbapenem chiron are selective inhibitors of human fatty acid amide hydrolase versus human monoacylglycerol lipase. J. Med. Chem., 2009, 52, 7054-7068.
132. Lenkowski, P. W.; Batts, T. W.; Smith, M. D.; Ko, S.; Jones, P. J.; Taylor, C. H.; McCusker, A. K.; Davis, G. C.; Hartmann, H. A.; White, H. S.; Brown, M. L.; Patel, M. K. A pharmacophore derived phenytoin analogue with increased affinity for slow inactivated sodium channels exhibits a desired anticonvulsant profile. Neuropharmacology, 2007, 52, 1044-1054.
133. Kanyonyo, M.; Govaerts, S. J.; Hermans, E.; Poupaert, J. H.; Lambert, D. M. 3-Alkyl-(5,5'-diphenyl)imidazolidinediones as new cannabinoid receptor ligands. Bioorg. Med. Chem. Lett., 1999, 9, 2233-2236.
134. Ooms, F.; Wouters, J.; Oscari, O.; Happaerts, T.; Bouchard, G.; Carrupt, P.; Testa, B.; Lambert, D. M. Exploration of the pharmacophore of 3-alkyl-5-arylimidazolidinediones as new CB1 cannabinoid receptor ligands and potential antagonists: synthesis, lipophilicity, affinity, and molecular modeling. J. Med. Chem., 2002, 45, 1748-1756.
135. Muccioli, G. G.; Martin, D.; Scriba, G. K. E.; Poppitz, W.; Poupaert, J. H.; Wouters, J.; Lambert, D. M. Substituted 5,5'- diphenyl-2-thioxoimidazolidin-4-one as CB1 cannabinoid receptor ligands: synthesis and pharmacological evaluation. J. Med. Chem., 2005, 48, 2509-2517.
136. Muccioli, G. G.; Wouters, J.; Charlier, C.; Scriba, G. K. E.; Pizza, T.; Di Pace, P.; De Martino, P.; Poppitz, W.; Poupaert, J. H.; Lambert, D. M. Synthesis and activity of 1,3,5-triphenylimidazolidine-2,4-diones and 1,3,5-triphenyl-2-thioxoimidazolidin-4- ones: characterization of new CB1 cannabinoid receptor inverse agonists/antagonists. J. Med. Chem., 2006, 49, 872-882.
137. Muccioli, G. G.; Fazio, N.; Scriba, G. K. E.; Poppitz, W.; Cannata, F.; Poupaert, J. H.; Wouters, J.; Lambert, D. M. Substituted 2- thioxoimidazolidin-4-ones and imidazolidine-2,4-diones as fatty acid amide hydrolase inhibitors templates. J. Med. Chem., 2006, 49, 417-425.
138. Michaux, C.; Muccioli, G. G.; Lambert, D. M.; Wouters, J. Binding mode of new (thio)hydantoin inhibitors of fatty acid amide hydrolase: Comparison with two original compounds, OL-92 and JP104. Bioorg. Med. Chem. Lett., 2006, 16, 4772-4776.
139. Wang, X.; Sarris, K.; Kage, K.; Zhang, D.; Brown, S. P.; Kolasa, T.; Surowy, C.; El Kouhen, O. F.; Muchmore, S. W.; Brioni, J. D.; Stewart, A. O. Synthesis and evaluation of benzothiazole-based analogues as novel, potent, and selective fatty acid amide hydrolase inhibitors. J. Med. Chem., 2009, 52, 170-180.
140. Yang, W.; Gao, X.; Wang, B. Boronic acid compounds as potential pharmaceutical agents. Med. Res. Rev., 2003, 23, 346-368.
141. Minkkilä, A.; Saario, S. M.; Käsnänen, H.; Leppänen, J.; Poso, A.; Nevalainen, T. Discovery of boronic acids as novel and potent inhibitors of fatty acid amide hydrolase. J. Med. Chem., 2008, 51, 7057-7060.
142. Schoenafinger, K.; Petry, S.; Müller, G.; Baringhaus, K.-H. Preparation of 3-phenyl-5-alkoxy-1,3,4-oxadiazol-2-ones as hormone-sensitive lipase inhibitors. PCT Int. Appl. 0166531, 2001.
143. Ben Ali, Y.; Chahinian, H.; Petry, S.; Muller, G.; Lebrun, R.; Verger, R.; Carriere, F.; Mandrich, L.; Rossi, M.; Manco, G.; Sarda, L.; Abousalham, A. Use of an inhibitor to identify members of the hormone-sensitive lipase Family. Biochemistry (NY), 2006, 45, 14183-14191.
144. Muccioli, G. G.; Labar, G.; Lambert, D. M. CAY10499, a Novel monoglyceride lipase inhibitor evidenced by an expeditious MGL assay. ChemBioChem, 2008, 9, 2704-2710.
145. Learmonth, D. A.; Kiss, L. E.; Beliaev, A.; Ferreira, H. D. S.; Silva, P. M. 5-O-substituted 3-N-phenyl-1,3,4-oxadiazolones as FAAH inhibitors and their preparation and use in the treatment of diseases. PCT Int. Appl. 2009084970, 2009.
146. Minkkilä, A.; Nevalainen, T.; Leppänen, J.; Saario, S. M. The hormone-sensitive lipase (HSL) inhibitor CAY10499 inhibits monoglyceride lipase (MGL). The Annual Symposium on the Cannabinoids ICRS, Aviemore, Scotland. 2008, P30.
147. Jonsson, K.; Vandevoorde, S.; Lambert, D. M.; Tiger, G.; Fowler, C. J. Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide. Br. J. Pharmacol., 2001, 133, 1263-1275.
148. Bisogno, T.; Melck, D.; De Petrocellis, L.; Bobrov, M. Y.; Gretskaya, N. M.; Bezuglov, V. V.; Sitachitta, N.; Gerwick, W. H.; Marzo, V. D. Arachidonoylserotonin and other novel inhibitors of fatty acid amide hydrolase. Biochem. Biophys. Res. Commun., 1998, 248, 515-522.
149. Beltramo, M.; Stella, N.; Calignano, A.; Lin, S. Y.; Makriyannis, A.; Piomelli, D. Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science, 1997, 277, 1094-1097.
150. Glaser, S. T.; Abumrad, N. A.; Fatade, F.; Kaczocha, M.; Studholme, K. M.; Deutsch, D. G. Evidence against the presence of an anandamide transporter. Proc. Natl. Acad. Sci. USA, 2003, 100, 4269-4274.
151. Maione, S.; Petrocellis, L.; Novellis, V.; Moriello, A. S.; Petrosino, S.; Palazzo, E.; Rossi, F. S.; Woodward, D. F.; 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, 766-781.
152. Ortar, G.; Cascio, M. G.; De Petrocellis, L.; Morera, E.; Rossi, F.; Schiano-Moriello, A.; Nalli, M.; de Novellis, V.; Woodward, D. F.; Maione, S.; Di Marzo, V. New N-arachidonoylserotonin analogues with potential Dual mechanism of action against pain. J. Med. Chem., 2007, 50, 6554-6569.
153. 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, 6806-6809.
154. De Petrocellis, L.; Bisogno, T.; Davis, J. B.; Pertwee, R. G.; Di Marzo, V. Overlap between the ligand recognition properties of the anandamide transporter and the VR1 vanilloid receptor: inhibitors of anandamide uptake with negligible capsaicin-like activity. FEBS Lett., 2000, 483, 52-56.
155. Fowler, C. J.; Tiger, G.; Stenström, A. Ibuprofen inhibits rat brain deamidation of anandamide at pharmacologically relevant concentrations. mode of inhibition and structure-activity relationship. J. Pharmacol. Exp. Ther. 1997, 283, 729-734.
156. Fowler, C. J.; Janson, U.; Johnson, R. M.; Wahlström, G.; Stenström, A.; Norström, Å.; Tiger, G. Inhibition of anandamide hydrolysis by the enantiomers of ibuprofen, ketorolac, and flurbiprofen. Arch. Biochem. Biophys, 1999, 362, 191-196.
157. Holt, S.; Paylor, B.; Boldrup, L.; Alajakku, K.; Vandevoorde, S.; Sundström, A.; Cocco, M. T.; Onnis, V.; Fowler, C. J. Inhibition of fatty acid amide hydrolase, a key endocannabinoid metabolizing enzyme, by analogues of ibuprofen and indomethacin. Eur. J. Pharmacol., 2007, 565, 26-36.
158. Lenman, A.; Fowler, C. J. Interaction of ligands for the peroxisome proliferator-activated receptor γ with the endocannabinoid system. Br. J. Pharmacol., 2007, 151, 1343-1351.
159. Thors, L.; Alajakku, K.; Fowler, C. J. The 'specific' tyrosine kinase inhibitor genistein inhibits the enzymic hydrolysis of anandamide: implications for anandamide uptake. Br. J. Pharmacol., 2007, 150, 951-960.
160. Patel, S.; Wohlfeil, E. R.; Rademacher, D. J.; Carrier, E. J.; Perry, L. J.; Kundu, A.; Falck, J. R.; Nithipatikom, K.; Campbell, W. B.; Hillard, C. J. The general anesthetic propofol increases brain Narachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase. Br. J. Pharmacol., 2003, 139, 1005-1013.
161. Tornqvist, H.; Belfrage, P. Purification and some properties of a monoacylglycerol-hydrolyzing enzyme of rat adipose tissue. J. Biol. Chem., 1976, 251, 813-819.
162. Karlsson, M.; Contreras, J. A.; Hellman, U.; Tornqvist, H.; Holm, C. cDNA cloning, tissue distribution, and identification of the catalytic triad of monoglyceride lipase. J. Biol. Chem., 1997, 272, 27218-27223.
163. Labar, G.; Bauvois, C.; Borel, F.; Ferrer, J.; Wouters, J.; Lambert, D. M. Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling. ChemBioChem, 2010, 11, 218-227.
164. 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, 663-673.
165. Saario, S. M.; Salo, O. M. H.; Nevalainen, T.; Poso, A.; Laitinen, J. T.; Järvinen, T.; Niemi, R. Characterization of the sulfhydrylsensitive site in the enzyme responsible for hydrolysis of 2- arachidonoyl-glycerol in rat cerebellar membranes. Chem. Biol., 2005, 12, 649-656.
166. Saario, S. M.; Poso, A.; Juvonen, R. O.; Järvinen, T.; Salo-Ahen, O. Fatty Acid amide hydrolase inhibitors from virtual screening of the endocannabinoid system. J. Med. Chem., 2006, 49, 4650-4656.
167. King, A.; Lodola, A.; Carmi, C.; Fu, J.; Mor, M.; Piomelli, D. A critical cysteine residue in monoacylglycerol lipase is targeted by a new class of isothiazolinone-based enzyme inhibitors. Br. J. Pharmacol., 2009, 157, 974-983.
168. Bowman, A.; Makriyannis, A. Refined homology model of monoacylglycerol lipase: toward a selective inhibitor. J. Comput. Aided Mol. Des., 2009, 23, 799-806.
169. Hofmann, B.; Tölzer, S.; Pelletier, I.; Altenbuchner, J.; van Pée, K. H.; Hecht, H. J. Structural investigation of the cofactor-free chloroperoxidases. J. Mol. Biol., 1998, 279, 889-900.
170. Zvonok, N.; Pandarinathan, L.; Williams, J.; Johnston, M.; Karageorgos, I.; Janero, D. R.; Krishnan, S. C.; Makriyannis, A. Covalent inhibitors of human monoacylglycerol lipase: ligandassisted characterization of the catalytic site by mass spectrometry and mutational analysis. Chem. Biol., 2008, 854-862.
171. Saario, S. M.; Palomäki, V.; Lehtonen, M.; Nevalainen, T.; Järvinen, T.; Laitinen, J. T. URB754 has no effect on the hydrolysis or signaling capacity of 2-AG in the rat brain. Chem. Biol., 2006, 13, 811-814.
172. Matuszak, N.; Muccioli, G. G.; Labar, G.; Lambert, D. M. Synthesis and in vitro evaluation of N-substituted maleimide derivatives as selective monoglyceride lipase inhibitors. J. Med. Chem., 2009, 52, 7410-7420.
173. Labar, G.; Bauvois, C.; Muccioli, G. G.; Wouters, J.; Lambert, D. M. Disulfiram is an inhibitor of human purified monoacylglycerol lipase, the enzyme regulating 2-arachidonoylglycerol signaling. ChemBioChem, 2007, 8, 1293-1297.
174. Kapanda, C. N.; Muccioli, G. G.; Labar, G.; Poupaert, J. H.; Lambert, D. M. bis(dialkylaminethiocarbonyl)disulfides as potent and selective monoglyceride lipase inhibitors. J. Med. Chem., 2009, 52, 7310-7314.
175. Saario, S. M.; Laitinen, J. T. Monoglyceride lipase as an enzyme hydrolyzing 2-arachidonoylglycerol. Chem. Biodiversity, 2007, 4, 1903-1913.
176. Lucas, K.; Kaplan-Machlis, B. Orlistat - a novel weight loss therapy. Ann. Pharmacother., 2001, 35, 314-328.
177. Bisogno, T.; Ortar, G.; Petrosino, S.; Morera, E.; Palazzo, E.; Nalli, M.; Maione, S.; Di Marzo, V. Development of a potent inhibitor of 2-arachidonoylglycerol hydrolysis with antinociceptive activity in vivo. Biochim. Biophys. Acta, Mol. Cell Biol. Lipids, 2009, 1791, 53-60.
178. Ortar, G.; Bisogno, T.; Ligresti, A.; Morera, E.; Nalli, M.; Di Marzo, V. Tetrahydrolipstatin analogues as modulators of endocannabinoid 2-arachidonoylglycerol metabolism. J. Med. Chem., 2008, 51, 6970-6979.
179. Hohmann, A. G.; Suplita, R. L.; Bolton, N. M.; Neely, M. H.; Fegley, D.; Mangieri, R.; Krey, J. F.; Walker, J. M.; 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, 1108-1112.
180. Vandevoorde, S.; Jonsson, K.; Labar, G.; Persson, E.; Lambert, D. M.; Fowler, C. J. Lack of selectivity of URB602 for 2- oleoylglycerol compared to anandamide hydrolysis in vitro. Br. J. Pharmacol., 2007, 150, 186-191.
181. Long, J. Z.; Li, W.; Booker, L.; Burston, J. J.; Kinsey, S. G.; Schlosburg, J. E.; Pavon, F. J.; Serrano, A. M.; Selley, D. E.; Parsons, L. H.; Lichtman, A. H.; Cravatt, B. F. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat. Chem. Biol., 2009, 5, 37-44.
182. Savinainen, J. R.; Megumi, Y.; Minkkilä, A.; Nevalainen, T.; Laitinen, J. T. Characterization of binding properties of monoglyceride lipase inhibitors by a versatile fluorescence-based technique. Anal. Biochem., 2010, 399, 132-134.
183. Holtfrerich, A.; Makharadze, T.; Lehr, M. High-performance liquid chromatography assay with fluorescence detection for the evaluation of inhibitors against human recombinant monoacylglycerol lipase. Anal. Biochem., 2010, 399, 218-224.
184. Long, J. Z.; Nomura, D. K.; Cravatt, B. F. Characterization of monoacylglycerol lipase inhibition reveals differences in central and peripheral endocannabinoid metabolism. Chem. Biol., 2009, 16, 744-753.
185. 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, 20270-20275.
186. Makriyannis, A.; Pandarinathan, L.; Zvonok, N.; Parkkari, T.; Chapman, L. Inhibitors of fatty acid amide hydrolase and monoacylglycerol lipase for modulation of cannabinoid receptors. PCT Int. Appl. 2009117444, 2009.
187. Hoornaert, C. Triazolopyridine carboxamide derivatives, preparation thereof and therapeutic use thereof. PCT Int. Appl. 2008145842, 2008.
188. Hoornaert, C. Derivatives of triazolopyridine carboxamides, particularly (piperazin-1-yl)(1,2,3-triazolo[4,5-b]pyridin-1-yl) methanones, their preparation and use as monoacyl glycerol lipase (MGL) inhibitors for treating MGL-related pathologies. Fr. Patent 2915197, 2008.
189. Ghafouri, N.; Tiger, G.; Razdan, R. K.; Mahadevan, A.; Pertwee, R. G.; Martin, B. R.; Fowler, C. J. Inhibition of monoacylglycerol lipase and fatty acid amide hydrolase by analogues of 2- arachidonoylglycerol. Br. J. Pharmacol., 2004, 143, 774-784.
190. Vandevoorde, S.; Saha, B.; Mahadevan, A.; Razdan, R. K.; Pertwee, R. G.; Martin, B. R.; Fowler, C. J. Influence of the degree of unsaturation of the acyl side chain upon the interaction of analogues of 1-arachidonoylglycerol with monoacylglycerol lipase and fatty acid amide hydrolase. Biochem. Biophys. Res. Commun., 2005, 337, 104-109.
191. Cisneros, J. A.; Vandevoorde, S.; Ortega-Gutierrez, S.; Paris, C.; Fowler, C. J.; Lopez-Rodriguez, M. Structure-activity relationship of a series of inhibitors of monoacylglycerol hydrolysis comparison with effects upon fatty acid amide hydrolase. J. Med. Chem. 2007, 50, 5012-5023.
192. Vadivel, S. K.; Vardarajan, S.; Duclos Jr., R. I.; Wood, J. T.; Guo, J.; Makriyannis, A. Conformationally constrained analogues of 2- arachidonoylglycerol. Bioorg. Med. Chem. Lett., 2007, 17, 5959-5963.
193. Magrioti, V.; Naxakis, G.; Hadjipavlou-Litina, D.; Makriyannis, A.; Kokotos, G. A novel monoacylglycerol lipase inhibitor with analgesic and anti-inflammatory activity. Bioorg. Med. Chem. Lett., 2008, 18, 5424-5427.
194. King, A. R.; Dotsey, E. Y.; Lodola, A.; Jung, K. M.; Ghomian, A.; Qiu, Y.; Fu, J.; Mor, M.; Piomelli, D. Discovery of potent and reversible monoacylglycerol lipase inhibitors. Chem. Biol., 2009, 16, 1045-1052.
195. Labar, G.; Michaux, C. Fatty acid amide hydrolase: from characterization to therapeutics. Chem. Biodiversity, 2007, 4, 1882-1902.
196. Chang, L.; Luo, L.; Palmer, J. A.; Sutton, S.; Wilson, S. J.; Barbier, A. J.; Breitenbucher, J. G.; Chaplan, S. R.; Webb, M. Inhibition of fatty acid amide hydrolase produces analgesia by multiple mechanisms. Br. J. Pharmacol., 2006, 148, 102-113.
197. Jayamanne, A.; Greenwood, R.; Mitchell, V. A.; Aslan, S.; Piomelli, D.; Vaughan, C. W. Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models. Br. J. Pharmacol., 2006, 147, 281-288.
198. Jhaveri, M. D.; Richardson, D.; Kendall, D. A.; Barrett, D. A.; Chapman, V. Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain. J. Neurosci., 2006, 26, 13318-13327.
199. Russo, R.; LoVerme, J.; La Rana, G.; Compton, T. R.; Parrott, J.; Duranti, A.; Tontini, A.; Mor, M.; Tarzia, G.; Calignano, A.; Piomelli, D. The fatty acid amide hydrolase inhibitor URB597 (cyclohexylcarbamic acid 3'-carbamoylbiphenyl-3-yl ester) Reduces neuropathic pain after oral administration in mice. J. Pharmacol. Exp. Ther., 2007, 322, 236-242.
200. 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, 21-38.
201. Bifulco, M.; Laezza, C.; Valenti, M.; Ligresti, A.; Portella, G.; Di Marzo, V. A new strategy to block tumor growth by inhibiting endocannabinoid inactivation. FASEB J., 2004, 18, 1606-1608.
202. Comelli, F.; Giagnoni, G.; Bettoni, I.; Colleoni, M.; Costa, B. The inhibition of monoacylglycerol lipase by URB602 showed an antiinflammatory and anti-nociceptive effect in a murine model of acute inflammation. Br. J. Pharmacol., 2007, 152, 787-794.
203. Burston, J. J.; Sim-Selley, L. J.; Harloe, J. P.; Mahadevan, A.; Razdan, R. K.; Selley, D. E.; Wiley, J. L. N-Arachidonyl maleimide potentiates the pharmacological and biochemical effects of the endocannabinoid 2-arachidonylglycerol through inhibition of monoacylglycerol lipase. J. Pharmacol. Exp. Ther., 2008, 327, 546-553.
204. Nomura, D. K.; Long, J. Z.; Niessen, S.; Hoover, H. S.; Ng, S.; Cravatt, B. F. Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell, 2010, 140, 49-61.