A Review on Structurally Diversified Synthesized Molecules as Monoacylglycerol Lipase Inhibitors and their Therapeutic uses

Abhishek      Kashyap; Suresh      Kumar; Rohit      Dutt
doi:10.2174/2589977514666220301111457
Abstract

Monoacylglycerol is a metabolic key serine hydrolase engaged in the regulation of the signalling network system of endocannabinoids, which is associated with various physiological processes like pain, inflammation, feeding cognition, and neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. The monoacylglycerol was also found to act as a regulator and the free fatty acid provider in the proliferation of cancer cells as well as numerous aggressive tumours such as colorectal cancer, neuroblastoma, and nasopharyngeal carcinoma. It also played an important role in increasing the concentration of specific lipids derived from free fatty acids like phosphatidic acid, lysophosphatidic acid, sphingosine-1-phosphate, and prostaglandin E2. These signalling lipids are associated with cell proliferation, survival, tumour cell migration, contribution to tumour development, maturation, and metastases. In this study, we present a review on structurally diverse MAGL inhibitors, their development, and their evaluation for different pharmacological activities.
Keywords: Amino acids, arachidonic acid, 2-arachidonoylglycerol, monoacylglycerol lipase, receptors, enzyme, endocannabinoid system, monoacylglycerol lipase inhibitors.
« Previous Next »
Graphical Abstract

[1] 
Mori W, Hatori A, Zhang Y, et al. Radiosynthesis and evalua-tion of a novel monoacylglycerol lipase radiotracer: 1,1,1,3,3,3-hexafluoropropan-2-yl-3-(1-benzyl-1H-pyrazol-3-yl)azetidine-1-[11C]carboxylate. Bioorg Med Chem  2019; 27(16): 3568-73.
[http://dx.doi.org/10.1016/j.bmc.2019.06.037] [PMID:  31278005] 
[2] 
Jung KM, Piomelli D.  Assay of monoacylglycerol lipase activity.
In: Thomas S, Ed. Methods in Molecular Biology. New Jersey:
Humana Press Inc. 2016; 1412: pp. 157-68.
[3] 
Castelli R, Scalvini L, Vacondio F, et al. Benzisothiazolinone derivatives as potent allosteric monoacylglycerol lipase in-hibitors that functionally mimic sulfenylation of regulatory cysteines. J Med Chem  2020; 63(3): 1261-80.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01679] [PMID:  31714779] 
[4] 
Dato FM, Neudörfl JM, Gütschow M, Goldfuss B, Pietsch M. ω- Quinazolinonylalkyl aryl ureas as reversible inhibitors of monoacylglycerol lipase. Bioorg Chem  2020; 94: 103352.
[http://dx.doi.org/10.1016/j.bioorg.2019.103352] [PMID:  31668797] 
[5] 
Chen Z, Mori W, Fu H, et al. Design, synthesis, and evalua-tion of 18F-labeled monoacylglycerol lipase inhibitors as novel positron emission tomography probes. J Med Chem  2019; 62(19): 8866-72.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00936] [PMID:  31518130] 
[6] 
Chen Z, Mori W, Deng X, et al. Design, synthesis, and eval-uation of reversible and irreversible monoacylglycerol lipase positron emission tomography (PET) tracers using a “tail switching” strategy on a piperazinyl azetidine skeleton. J Med Chem  2019; 62(7): 3336-53.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01778] [PMID:  30829483] 
[7] 
Cisar JS, Weber OD, Clapper JR, et al. Identification of ABX-1431, a selective inhibitor of monoacylglycerol lipase and clinical candidate for treatment of neurological disorders. J Med Chem  2018; 61(20): 9062-84.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00951] [PMID:  30067909] 
[8] 
McAllister LA, Butler CR, Mente S, et al. Discovery of tri-fluoromethyl glycol carbamates as potent and selective cova-lent monoacylglycerol lipase (MAGL) inhibitors for treatment of neuroinflammation. J Med Chem  2018; 61(7): 3008-26.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00070] [PMID:  29498843] 
[9] 
Karageorgos I, Silin VI, Zvonok N, Marino J, Janero DR, Makriyannis A. The role of human monoacylglycerol lipase (hMAGL) binding pocket in breakup of unsaturated phospho-lipid membranes. Anal Biochem  2017; 536: 90-5.
[http://dx.doi.org/10.1016/j.ab.2017.08.009] [PMID:  28822686] 
[10] 
Tuo W, Leleu-Chavain N, Spencer J, Sansook S, Millet R, Chavatte P. Therapeutic potential of fatty acid amide hydro-lase, monoacylglycerol lipase, and N-acylethanolamine acid amidase inhibitors. J Med Chem  2017; 60(1): 4-46.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00538] [PMID:  27766867] 
[11] 
Lamani M, Malamas MS, Farah SI, et al. Piperidine and pi-perazine inhibitors of fatty acid amide hydrolase targeting ex-citotoxic pathology. Bioorg Med Chem  2019; 27(23): 15096.
[12] 
Hattori Y, Aoyama K, Maeda J, et al. Design, synthesis, and evaluation of (4 r)-1-{3-[2-(18f)fluoro-4-methylpyridin-3-yl]phenyl}-4-[4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl]pyrrolidin-2-one ([18f] t-401) as a novel positron-emission tomography imaging agent for monoacylglycerol li-pase. J Med Chem  2019; 62(5): 2362-75.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01576] [PMID:  30753069] 
[13] 
Kind L, Kursula P. Structural properties and role of the endo-cannabinoid lipases ABHD6 and ABHD12 in lipid signalling and disease. Amino Acids  2019; 51(2): 151-74.
[http://dx.doi.org/10.1007/s00726-018-2682-8] [PMID:  30564946] 
[14] 
Granchi C, Caligiuri I, Bertelli E, et al. Development of ter-phenyl-2-methyloxazol-5(4H)-one derivatives as selective re-versible MAGL inhibitors. J Enzyme Inhib Med Chem  2017; 32(1): 1240-52.
[http://dx.doi.org/10.1080/14756366.2017.1375484] [PMID:  28936880] 
[15] 
Granchi C, Rizzolio F, Palazzolo S, et al. Structural optimiza-tion of 4-chlorobenzoylpiperidine derivatives for the devel-opment of potent, reversible, and selective monoacylglycerol lipase (MAGL) inhibitors. J Med Chem  2016; 59(22): 10299-314.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01459] [PMID:  27809504] 
[16] 
Wang L, Mori W, Cheng R, et al. Synthesis and preclinical evaluation of sulfonamido-based [(11)C-Carbonyl]-carbamates and ureas for imaging monoacylglycerol lipase. Theranostics  2016; 6(8): 1145-59.
[http://dx.doi.org/10.7150/thno.15257] [PMID:  27279908] 
[17] 
Poli G, Lapillo M, Jha V, et al. Computationally driven dis-covery of phenyl(piperazin-1-yl)methanone derivatives as re-versible monoacylglycerol lipase (MAGL) inhibitors. J Enzyme Inhib Med Chem  2019; 34(1): 589-96.
[http://dx.doi.org/10.1080/14756366.2019.1571271] [PMID:  30696302] 
[18] 
Granchi C, Lapillo M, Glasmacher S, et al. Optimization of a benzoylpiperidine class identifies a highly potent and selec-tive reversible monoacylglycerol lipase (MAGL) inhibitor. J Med Chem  2019; 62(4): 1932-58.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01483] [PMID:  30715876] 
[19] 
Afzal O, Akhtar MS, Kumar S, Ali MR, Jaggi M, Bawa S. Hit to lead optimization of a series of N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamides as monoacylglycerol lipase inhibitors with potential anticancer activity. Eur J Med Chem  2016; 121: 318-30.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.038] [PMID:  27267002] 
[20] 
Miceli M, Casati S, Ottria R, et al. Set-up and validation of a high throughput screening method for human monoacylglyc-erol lipase (MAGL) based on a new red fluorescent probe. Molecules  2019; 24(12): E2241.
[http://dx.doi.org/10.3390/molecules24122241] [PMID:  31208066] 
[21] 
Ahamed M, Attili B, van Veghel D, et al. Synthesis and pre-clinical evaluation of [11C]MA-PB-1 for in vivo imaging of brain monoacylglycerol lipase (MAGL). Eur J Med Chem  2017; 136: 104-13.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.066] [PMID:  28486208] 
[22] 
Riccardi L, Arencibia JM, Bono L, Armirotti A, Girotto S, De Vivo M. Lid domain plasticity and lipid flexibility modulate enzyme specificity in human monoacylglycerol lipase. Biochim Biophys Acta Mol Cell Biol Lipids  2017; 1862(5): 441-51.
[http://dx.doi.org/10.1016/j.bbalip.2017.01.002] [PMID:  28088576] 
[23] 
Scalvini L, Vacondio F, Bassi M, et al. Free-energy studies reveal a possible mechanism for oxidation-dependent inhibi-tion of MGL. Sci Rep  2016; 6: 31046.
[http://dx.doi.org/10.1038/srep31046] [PMID:  27499063] 
[24] 
Liu X, Chen Y, Vickstrom CR, et al. Coordinated regulation of endocannabinoid-mediated retrograde synaptic suppres-sion in the cerebellum by neuronal and astrocytic monoacyl-glycerol lipase. Sci Rep  2016; 6: 35829.
[http://dx.doi.org/10.1038/srep35829] [PMID:  27775008] 
[25] 
Lauria S, Perrotta C, Casati S, et al. Design, synthesis, molec-ular modelling and in vitro cytotoxicity analysis of novel car-bamate derivatives as inhibitors of monoacylglycerol lipase. Bioorg Med Chem  2018; 26(9): 2561-72.
[26] 
Patel JZ, Nevalainen TJ, Savinainen JR, et al. Optimization of 1,2,5-thiadiazole carbamates as potent and selective ABHD6 inhibitors. ChemMedChem  2015; 10(2): 253-65.
[http://dx.doi.org/10.1002/cmdc.201402453] [PMID:  25504894] 
[27] 
Kohnz RA, Nomura DK. Chemical approaches to therapeuti-cally target the metabolism and signaling of the endocanna-binoid 2-AG and eicosanoids. Chem Soc Rev  2014; 43(19): 6859-69.
[http://dx.doi.org/10.1039/C4CS00047A] [PMID:  24676249] 
[28] 
Aghazadeh Tabrizi M, Baraldi PG, Baraldi S, et al. Discovery of 1,5-diphenylpyrazole-3-carboxamide derivatives as potent, reversible, and selective monoacylglycerol lipase (MAGL) in-hibitors. J Med Chem  2018; 61(3): 1340-54.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01845] [PMID:  29309142] 
[29] 
Jiang M, van der Stelt M. Activity-based protein profiling delivers selective drug candidate ABX-1431, a monoacylglyc-erol lipase inhibitor, to control lipid metabolism in neurologi-cal disorders. J Med Chem  2018; 61(20): 9059-61.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01405] [PMID:  30354159] 
[30] 
Zhang L, Butler CR, Maresca KP, et al. Identification and development of an irreversible monoacylglycerol lipase (MAGL) positron emission tomography (PET) radioligand with high specificity. J Med Chem  2019; 62(18): 8532-43.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00847] [PMID:  31483137] 
[31] 
Islam MS, Wang C, Zheng J, Paudyal N, Zhu Y, Sun H. The potential role of tubeimosides in cancer prevention and treat-ment. Eur J Med Chem  2019; 162: 109-21.
[http://dx.doi.org/10.1016/j.ejmech.2018.11.001] [PMID:  30439592] 
[32] 
Cheng B, Yuan WE, Su J, Liu Y, Chen J. Recent advances in small molecule based cancer immunotherapy. Eur J Med Chem  2018; 157: 582-98.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.028] [PMID:  30125720] 
[33] 
Sherer C, Snape TJ. Heterocyclic scaffolds as promising anti-cancer agents against tumours of the central nervous system: Exploring the scope of indole and carbazole derivatives. Eur J Med Chem  2015; 97: 552-60.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.007] [PMID:  25466446] 
[34] 
Ma M, Bai J, Ling Y, et al. Monoacylglycerol lipase inhibitor JZL184 regulates apoptosis and migration of colorectal cancer cells. Mol Med Rep  2016; 13(3): 2850-6.
[http://dx.doi.org/10.3892/mmr.2016.4829] [PMID:  26847687] 
[35] 
Bononi G, Granchi C, Lapillo M, et al. Discovery of long-chain salicylketoxime derivatives as monoacylglycerol lipase (MAGL) inhibitors. Eur J Med Chem  2018; 157: 817-36.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.038] [PMID:  30144699] 
[36] 
Granchi C, Rizzolio F, Caligiuri I, et al. Rational development of MAGL inhibitors. Methods Mol Biol  2018; 1824: 335-46.
[http://dx.doi.org/10.1007/978-1-4939-8630-9_20] [PMID:  30039417] 
[37] 
Nomura DK, Long JZ, Niessen S, Hoover HS, Ng SW, Cravatt BF. Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell  2010; 140(1): 49-61.
[http://dx.doi.org/10.1016/j.cell.2009.11.027] [PMID:  20079333] 
[38] 
Tuccinardi T, Granchi C, Rizzolio F, et al. Identification and characterization of a new reversible MAGL inhibitor. Bioorg Med Chem  2014; 22(13): 3285-91.
[http://dx.doi.org/10.1016/j.bmc.2014.04.057] [PMID:  24853323] 
[39] 
Zhang J, Liu Z, Lian Z, et al. Monoacylglycerol lipase: A novel potential therapeutic target and prognostic indicator for hepatocellular carcinoma. Sci Rep  2016; 6: 35784.
[http://dx.doi.org/10.1038/srep35784] [PMID:  27767105] 
[40] 
Granchi C, Rizzolio F, Bordoni V, et al. 4-Aryliden-2-methyloxazol-5 (4H)-one as a new scaffold for selective re-versible MAGL inhibitors. J Enzyme Inhib Med Chem  2016; 31(1): 137-46.
[http://dx.doi.org/10.3109/14756366.2015.1010530] [PMID:  25669350] 
[41] 
Afzal O, Kumar S, Kumar R, Firoz A, Jaggi M, Bawa S. Dock-ing based virtual screening and molecular dynamics study to identify potential monoacylglycerol lipase inhibitors. Bioorg Med Chem Lett  2014; 24(16): 3986-96.
[http://dx.doi.org/10.1016/j.bmcl.2014.06.029] [PMID:  25011912] 
[42] 
Wise LE, Long KA, Abdullah RA, Long JZ, Cravatt BF, Lichtman AH. Dual fatty acid amide hydrolase and mono-acylglycerol lipase blockade produces THC-like morris water maze deficits in mice. Proceedings of the ACS Chemical Neu-roscience.  Vol. 3: 369-78.
[http://dx.doi.org/10.1021/cn200130s] 
[43] 
Alapafuja SO, Malamas MS, Shukla V, et al. Synthesis and evaluation of potent and selective MGL inhibitors as a glau-coma treatment. Bioorg Med Chem  2019; 27(1): 55-64.
[44] 
Tyukhtenko S, Rajarshi G, Karageorgos I, et al. Effects of distal mutations on the structure, dynamics and catalysis of human monoacylglycerol lipase. Sci Rep  2018; 8(1): 1719.
[http://dx.doi.org/10.1038/s41598-017-19135-7] [PMID:  29379013] 
[45] 
Berdan CA, Erion KA, Burritt NE, Corkey BE, Deeney JT. Inhibition of monoacylglycerol lipase activity decreases glu-cose-stimulated insulin secretion in INS-1 (832/13) cells and rat islets. PLoS One  2016; 11(2): e0149008.
[http://dx.doi.org/10.1371/journal.pone.0149008] [PMID:  26867016] 
[46] 
King AR, Dotsey EY, Lodola A, et al. Discovery of potent and reversible monoacylglycerol lipase inhibitors. Chem Biol  2009; 16(10): 1045-52.
[http://dx.doi.org/10.1016/j.chembiol.2009.09.012] [PMID:  19875078] 
[47] 
Scalvini L, Piomelli D, Mor M. Monoglyceride lipase: Struc-ture and inhibitors. Chem Phys Lipids  2016; 197: 13-24.
[http://dx.doi.org/10.1016/j.chemphyslip.2015.07.011] [PMID:  26216043] 
[48] 
Schalk-Hihi C, Schubert C, Alexander R, et al. Crystal struc-ture of a soluble form of human monoglyceride lipase in complex with an inhibitor at 1.35 Å resolution. Protein Sci  2011; 20(4): 670-83.
[http://dx.doi.org/10.1002/pro.596] [PMID:  21308848] 
[49] 
Labar G, Bauvois C, Borel F, Ferrer J-L, Wouters J, Lambert DM. Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling. ChemBioChem  2010; 11(2): 218-27.
[http://dx.doi.org/10.1002/cbic.200900621] [PMID:  19957260] 
[50] 
Aida J, Fushimi M, Kusumoto T, et al. Design, synthesis, and evaluation of piperazinyl pyrrolidin-2-ones as a novel series of reversible monoacylglycerol lipase inhibitors. J Med Chem  2018; 61(20): 9205-17.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00824] [PMID:  30251836] 
[51] 
King AR, Duranti A, Tontini A, et al. URB602 inhibits mono-acylglycerol lipase and selectively blocks 2-arachidonoylglycerol degradation in intact brain slices. Chem Biol  2007; 14(12): 1357-65.
[http://dx.doi.org/10.1016/j.chembiol.2007.10.017] [PMID:  18096504] 
[52] 
Comelli F, Giagnoni G, Bettoni I, Colleoni M, Costa B. The inhibition of monoacylglycerol lipase by URB602 showed an anti-inflammatory and anti-nociceptive effect in a murine model of acute inflammation. Br J Pharmacol  2007; 152(5): 787-94.
[http://dx.doi.org/10.1038/sj.bjp.0707425] [PMID:  17700715] 
[53] 
Xiong Y, Yao H, Cheng Y, Gong D, Liao X, Wang R. Effects of monoacylglycerol lipase inhibitor URB602 on lung ische-mia-reperfusion injury in mice. Biochem Biophys Res Commun  2018; 506(3): 578-84.
[http://dx.doi.org/10.1016/j.bbrc.2018.10.098] [PMID:  30366666] 
[54] 
Long JZ, Li W, Booker L, et al. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid be-havioral effects. Nat Chem Biol  2009; 5(1): 37-44.
[http://dx.doi.org/10.1038/nchembio.129] [PMID:  19029917] 
[55] 
Ghosh S, Wise LE, Chen Y, et al. The monoacylglycerol li-pase inhibitor JZL184 suppresses inflammatory pain in the mouse carrageenan model. Proceedings of the Life Sciences.  Vol. 92: 498-505.
[http://dx.doi.org/10.1016/j.lfs.2012.06.020] 
[56] 
Long JZ, Nomura DK, Cravatt BF. Characterization of mono-acylglycerol lipase inhibition reveals differences in central and peripheral endocannabinoid metabolism. Chem Biol  2009; 16(7): 744-53.
[http://dx.doi.org/10.1016/j.chembiol.2009.05.009] [PMID:  19635411] 
[57] 
Rahmani MR, Shamsizadeh A, Moghadam-Ahmadi A, Kaeidi A, Allahtavakoli M. Monoacylglycerol lipase inhibitor, JZL-184, confers neuroprotection in the mice middle cerebral ar-tery occlusion model of stroke. Life Sci  2018; 198: 143-8.
[http://dx.doi.org/10.1016/j.lfs.2018.02.036] [PMID:  29496497] 
[58] 
Marino S, de Ridder D, Bishop RT, et al. Paradoxical effects of JZL184, an inhibitor of monoacylglycerol lipase, on bone remodelling in healthy and cancer-bearing mice. EBioMedicine  2019; 44: 452-66.
[http://dx.doi.org/10.1016/j.ebiom.2019.05.048] [PMID:  31151929] 
[59] 
Kinsey SG, Wise LE, Ramesh D, et al. Repeated low-dose administration of the monoacylglycerol lipase inhibitor JZL184 retains cannabinoid receptor type 1-mediated antino-ciceptive and gastroprotective effects. J Pharmacol Exp Ther  2013; 345(3): 492-501.
[http://dx.doi.org/10.1124/jpet.112.201426] [PMID:  23412396] 
[60] 
Long JZ, Jin X, Adibekian A, Li W, Cravatt BF. Characteriza-tion of tunable piperidine and piperazine carbamates as in-hibitors of endocannabinoid hydrolases. J Med Chem  2010; 53(4): 1830-42.
[http://dx.doi.org/10.1021/jm9016976] [PMID:  20099888] 
[61] 
Chang JW, Niphakis MJ, Lum KM, et al. Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates. Chem Biol  2012; 19(5): 579-88.
[http://dx.doi.org/10.1016/j.chembiol.2012.03.009] [PMID:  22542104] 
[62] 
Pasquarelli N, Porazik C, Hanselmann J, Weydt P, Ferger B, Witting A. Comparative biochemical characterization of the monoacylglycerol lipase inhibitor KML29 in brain, spinal cord, liver, spleen, fat and muscle tissue. Neuropharmacology  2015; 91: 148-56.
[http://dx.doi.org/10.1016/j.neuropharm.2014.12.001] [PMID:  25497453] 
[63] 
Ignatowska-Jankowska BM, Ghosh S, Crowe MS, et al. In vivo characterization of the highly selective monoacylglycerol lipase inhibitor KML29: antinociceptive activity without can-nabimimetic side effects. Br J Pharmacol  2014; 171(6): 1392-407.
[http://dx.doi.org/10.1111/bph.12298] [PMID:  23848221] 
[64] 
Chang JW, Cognetta AB III, Niphakis MJ, Cravatt BF. Proteo-me-wide reactivity profiling identifies diverse carbamate chemotypes tuned for serine hydrolase inhibition. ACS Chem Biol  2013; 8(7): 1590-9.
[http://dx.doi.org/10.1021/cb400261h] [PMID:  23701408] 
[65] 
Niphakis MJ, Cognetta AB, Chang JW, et al. Evaluation of NHS carbamates as a potent and selective class of endocan-nabinoid hydrolase inhibitors. ACS Chem Neurosci  2013; 4(9): 1322-32.
[http://dx.doi.org/10.1021/cn400116z] 
[66] 
Zanfirescu A, Ungurianu A, Mihai DP, Radulescu D, Ni-tulescu GM. Targeting monoacylglycerol lipase in pursuit of therapies for neurological and neurodegenerative diseases. Molecules  2021; 26(18): 26.
[http://dx.doi.org/10.3390/molecules26185668] [PMID:  34577139] 
[67] 
Griebel G, Pichat P, Beeské S, et al. 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: 7642.
[http://dx.doi.org/10.1038/srep07642] [PMID:  25560837] 
[68] 
Butler CR, Beck EM, Harris A, et al. Azetidine and piperidine carbamates as efficient, covalent inhibitors of monoacylglyc-erol lipase. J Med Chem  2017; 60(23): 9860-73.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01531] [PMID:  29148769] 
[69] 
Cheng R, Mori W, Ma L, et al. In vitro and in vivo evaluation of 11C-labeled azetidinecarboxylates for imaging monoacyl-glycerol lipase by PET imaging studies. J Med Chem  2018; 61(6): 2278-91.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01400] [PMID:  29481079] 
[70] 
 Central pain study for ABX-1431 - Full text view - clinicaltrials.
Available from: https://www.clinicaltrials.gov/ct2/show/NCT03138421?term=ABX1431&cond=Cancer&draw=2&rank=1 (Accessed Nov 28, 2021).
[71] 
Bertrand T, Augé F, Houtmann J, et al. Structural basis for human monoglyceride lipase inhibition. J Mol Biol  2010; 396(3): 663-73.
[http://dx.doi.org/10.1016/j.jmb.2009.11.060] [PMID:  19962385] 
[72] 
Morera L, Labar G, Ortar G, Lambert DM. Development and characterization of endocannabinoid hydrolases FAAH and MAGL inhibitors bearing a benzotriazol-1-yl carboxamide scaffold. Bioorg Med Chem  2012; 20(21): 6260-75.
[http://dx.doi.org/10.1016/j.bmc.2012.09.011] [PMID:  23036333] 
[73] 
Aaltonen N, Savinainen JR, Ribas CR, et al. Piperazine and piperidine triazole ureas as ultrapotent and highly selective inhibitors of monoacylglycerol lipase. Chem Biol  2013; 20(3): 379-90.
[http://dx.doi.org/10.1016/j.chembiol.2013.01.012] [PMID:  23521796] 
[74] 
Patel JZ, Ahenkorah S, Vaara M, et al. Loratadine analogues as MAGL inhibitors. Bioorg Med Chem Lett  2015; 25(7): 1436-42.
[http://dx.doi.org/10.1016/j.bmcl.2015.02.037] [PMID:  25752982] 
[75] 
Kapanda CN, Masquelier J, Labar G, Muccioli GG, Poupaert JH, Lambert DM. Synthesis and pharmacological evaluation of 2,4-dinitroaryldithiocarbamate derivatives as novel mono-acylglycerol lipase inhibitors. J Med Chem  2012; 55(12): 5774-83.
[http://dx.doi.org/10.1021/jm3006004] [PMID:  22651858] 
[76] 
Saario SM, Salo OMH, Nevalainen T, et al. Characterization of the sulfhydryl-sensitive site in the enzyme responsible for hydrolysis of 2-arachidonoyl-glycerol in rat cerebellar mem-branes. Chem Biol  2005; 12(6): 649-56.
[http://dx.doi.org/10.1016/j.chembiol.2005.04.013] [PMID:  15975510] 
[77] 
Kapanda CN, Muccioli GG, Labar G, Poupaert JH, Lambert DM. Bis(dialkylaminethiocarbonyl)disulfides as potent and selective monoglyceride lipase inhibitors. J Med Chem  2009; 52(22): 7310-4.
[http://dx.doi.org/10.1021/jm901323s] [PMID:  19883085] 
[78] 
King AR, 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(6): 974-83.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00276.x] [PMID:  19486005] 
[79] 
 Heteroaromatic and aromatic piperazinyl azetidinyl amides as
monoacylglycerol lipase inhibitor. WO2010124121A1, Available
from: https://patents.google.com/patent/WO2010124121A1/en (Accessed
Apr 5, 2021).
[80] 
 Heteroaromatic and aromatic piperazinyl azetidinyl amides as
monoacylglycerol lipase inhibitors. WO2010124122A1, Available
from: https://patents.google.com/patent/WO2010124122A1/en (Accessed
Mar 24, 2021).
Rights & Permissions Print Cite
Article Metrics
61
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/2589977514666220301111457	Print ISSN 2589-9775
Publisher Name Bentham Science Publisher	Online ISSN 2589-9783
Current Drug Research Reviews

A Review on Structurally Diversified Synthesized Molecules as Monoacylglycerol Lipase Inhibitors and their Therapeutic uses

Abstract

Graphical Abstract

Related Journals

Related Books

Related Articles
