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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Impact of Cannabinoid Receptors in the Design of Therapeutic Agents against Human Ailments

Author(s): Ankush Kumar, Ojasvi Gupta, Rohit Bhatia* and VikramDeep Monga*

Volume 23, Issue 19, 2023

Published on: 19 May, 2023

Page: [1807 - 1834] Pages: 28

DOI: 10.2174/1568026623666230502120956

Price: $65

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Abstract

The Cannabinoid (CB) signalling cascade is widely located in the human body and is associated with several pathophysiological processes. The endocannabinoid system comprises cannabinoid receptors CB1 and CB2, which belong to G-protein Coupled Receptors (GPCRs). CB1 receptors are primarily located on nerve terminals, prohibiting neurotransmitter release, whereas CB2 are present predominantly on immune cells, causing cytokine release. The activation of CB system contributes to the development of several diseases which might have lethal consequences, such as CNS disorders, cancer, obesity, and psychotic disorders on human health. Clinical evidence revealed that CB1 receptors are associated with CNS ailments such as Alzheimer’s disease, Huntington’s disease, and multiple sclerosis, whereas CB2 receptors are primarily connected with immune disorders, pain, inflammation, etc. Therefore, cannabinoid receptors have been proved to be promising targets in therapeutics and drug discovery. Experimental and clinical outcomes have disclosed the success story of CB antagonists, and several research groups have framed newer compounds with the binding potential to these receptors. In the presented review, we have summarized variously reported heterocycles with CB receptor agonistic/antagonistic properties against CNS disorders, cancer, obesity, and other complications. The structural activity relationship aspects have been keenly described along with enzymatic assay data. The specific outcomes of molecular docking studies have also been highlighted to get insights into the binding patterns of the molecules to CB receptors.

Keywords: Cannabinoid, Cancer, Obesity, Antagonists, Heterocycles, Docking.

Graphical Abstract
[1]
ElSohly, M.A.; Slade, D. Chemical constituents of marijuana: The complex mixture of natural cannabinoids. Life Sci., 2005, 78(5), 539-548.
[http://dx.doi.org/10.1016/j.lfs.2005.09.011] [PMID: 16199061]
[2]
Gertsch, J.; Pertwee, R.G.; Di Marzo, V. Phytocannabinoids beyond the Cannabis plant - do they exist? Br. J. Pharmacol., 2010, 160(3), 523-529.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00745.x] [PMID: 20590562]
[3]
Malfitano, A.M. What we know and do not know about the cannabinoid receptor 2 (CB2). In: Seminars in immunology; Elsevier, 2014.
[http://dx.doi.org/10.1016/j.smim.2014.04.002]
[4]
Keeney, B.K.; Raichlen, D.A.; Meek, T.H.; Wijeratne, R.S.; Middleton, K.M.; Gerdeman, G.L.; Garland, T. Jr Differential response to a selective cannabinoid receptor antagonist (SR141716: rimonabant) in female mice from lines selectively bred for high voluntary wheel-running behaviour. Behav. Pharmacol., 2008, 19(8), 812-820.
[http://dx.doi.org/10.1097/FBP.0b013e32831c3b6b] [PMID: 19020416]
[5]
Koethe, D.; Gerth, C.W.; Neatby, M.A.; Haensel, A.; Thies, M.; Schneider, U.; Emrich, H.M.; Klosterkötter, J.; Schultze-Lutter, F.; Leweke, F.M. Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness. Schizophr. Res., 2006, 88(1-3), 142-150.
[http://dx.doi.org/10.1016/j.schres.2006.07.023] [PMID: 17005373]
[6]
Patel, P.N.; Pathak, R. Rimonabant: A novel selective cannabinoid-1 receptor antagonist for treatment of obesity. Am. J. Health Syst. Pharm., 2007, 64(5), 481-489.
[http://dx.doi.org/10.2146/060258] [PMID: 17322160]
[7]
Nam, G.; Jeong, S.K.; Park, B.M.; Lee, S.H.; Kim, H.J.; Hong, S.P.; Kim, B.; Kim, B.W. Selective cannabinoid receptor-1 agonists regulate mast cell activation in an oxazolone-induced atopic dermatitis model. Ann. Dermatol., 2016, 28(1), 22-29.
[http://dx.doi.org/10.5021/ad.2016.28.1.22] [PMID: 26848215]
[8]
Grotenhermen, F. Cannabis Healing: A Guide to the Therapeutic Use of CBD, THC, and Other Cannabinoids; Simon and Schuster, 2020.
[9]
Klumpers, L.E.; Fridberg, M.; de Kam, M.L.; Little, P.B.; Jensen, N.O.; Kleinloog, H.D.; Elling, C.E.; van Gerven, J.M.A. Peripheral selectivity of the novel cannabinoid receptor antagonist TM38837 in healthy subjects. Br. J. Clin. Pharmacol., 2013, 76(6), 846-857.
[http://dx.doi.org/10.1111/bcp.12141] [PMID: 23601084]
[10]
Rhee, M.H.; Vogel, Z.; Barg, J.; Bayewitch, M.; Levy, R.; Hanuš, L.; Breuer, A.; Mechoulam, R. Cannabinol derivatives: Binding to cannabinoid receptors and inhibition of adenylylcyclase. J. Med. Chem., 1997, 40(20), 3228-3233.
[http://dx.doi.org/10.1021/jm970126f] [PMID: 9379442]
[11]
Pertwee, R.G. The diverse CB 1 and CB 2 receptor pharmacology of three plant cannabinoids: Δ 9 -tetrahydrocannabinol, cannabidiol and Δ 9 -tetrahydrocannabivarin. Br. J. Pharmacol., 2008, 153(2), 199-215.
[http://dx.doi.org/10.1038/sj.bjp.0707442] [PMID: 17828291]
[12]
Fernández-Ruiz, J.; García, C.; Sagredo, O.; Gómez-Ruiz, M.; de Lago, E. The endocannabinoid system as a target for the treatment of neuronal damage. Expert Opin. Ther. Targets, 2010, 14(4), 387-404.
[http://dx.doi.org/10.1517/14728221003709792] [PMID: 20230193]
[13]
Bosier, B.; Muccioli, G.G.; Hermans, E.; Lambert, D.M. Functionally selective cannabinoid receptor signalling: Therapeutic implications and opportunities. Biochem. Pharmacol., 2010, 80(1), 1-12.
[http://dx.doi.org/10.1016/j.bcp.2010.02.013] [PMID: 20206137]
[14]
Kendall, D.A.; Yudowski, G.A. Cannabinoid receptors in the central nervous system: their signaling and roles in disease. Front. Cell. Neurosci., 2017, 10, 294.
[http://dx.doi.org/10.3389/fncel.2016.00294] [PMID: 28101004]
[15]
Seddon, A.M.; Casey, D.; Law, R.V.; Gee, A.; Templer, R.H.; Ces, O. Drug interactions with lipid membranes. Chem. Soc. Rev., 2009, 38(9), 2509-2519.
[http://dx.doi.org/10.1039/b813853m] [PMID: 19690732]
[16]
Ryan, D.; Drysdale, A.J.; Lafourcade, C.; Pertwee, R.G.; Platt, B. Cannabidiol targets mitochondria to regulate intracellular Ca2+ levels. J. Neurosci., 2009, 29(7), 2053-2063.
[http://dx.doi.org/10.1523/JNEUROSCI.4212-08.2009] [PMID: 19228959]
[17]
Mead, A. Legal and regulatory issues governing cannabis and cannabis-derived products in the United States. Front. Plant Sci., 2019, 10, 697.
[http://dx.doi.org/10.3389/fpls.2019.00697] [PMID: 31263468]
[18]
Nguyen, P.T.; Selley, D.E.; Sim-Selley, L.J. Statistical parametric mapping reveals ligand and region-specific activation of g-proteins by cb1 receptors and non-cb1 sites in the 3d reconstructed mouse brain. Neuroimage, 2010, 52(4), 1243-1251.
[http://dx.doi.org/10.1016/j.neuroimage.2010.04.259] [PMID: 20451624]
[19]
Onaivi, E.S. Endocannabinoids: The brain and body’s marijuana and beyond. In: Endocannabinoid receptor genetics and marijuana use; Taylor & Francis: Boca Raton, 2006; pp. 57-118.
[20]
Wiley, J.L.; Martin, B.R. Cannabinoid pharmacology: Implications for additional cannabinoid receptor subtypes. Chem. Phys. Lipids, 2002, 121(1-2), 57-63.
[http://dx.doi.org/10.1016/S0009-3084(02)00146-9] [PMID: 12505690]
[21]
Devane, W.A.; Hanuš, 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(5090), 1946-1949.
[http://dx.doi.org/10.1126/science.1470919] [PMID: 1470919]
[22]
Compton, D.R.; Gold, L.H.; Ward, S.J.; Balster, R.L.; Martin, B.R. Aminoalkylindole analogs: Cannabimimetic activity of a class of compounds structurally distinct from delta 9-tetrahydrocannabinol. J. Pharmacol. Exp. Ther., 1992, 263(3), 1118-1126.
[PMID: 1335057]
[23]
Zou, S.; Kumar, U. Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. Int. J. Mol. Sci., 2018, 19(3), 833.
[http://dx.doi.org/10.3390/ijms19030833] [PMID: 29533978]
[24]
Elsebai, M.F.; Rempel, V.; Schnakenburg, G.; Kehraus, S.; Müller, C.E.; König, G.M. Identification of a potent and selective cannabinoid CB1 receptor antagonist from Auxarthron reticulatum. ACS Med. Chem. Lett., 2011, 2(11), 866-869.
[http://dx.doi.org/10.1021/ml200183z] [PMID: 24900275]
[25]
Hanisch, U.K.; Kettenmann, H. Microglia: Active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci., 2007, 10(11), 1387-1394.
[http://dx.doi.org/10.1038/nn1997] [PMID: 17965659]
[26]
Compton, D.R.; Aceto, M.D.; Lowe, J.; Martin, B.R. In vivo characterization of a specific cannabinoid receptor antagonist (SR141716A): Inhibition of delta 9-tetrahydrocannabinol-induced responses and apparent agonist activity. J. Pharmacol. Exp. Ther., 1996, 277(2), 586-594.
[PMID: 8627535]
[27]
Devane, W.A.; Dysarz, F.A., III; Johnson, M.R.; Melvin, L.S.; Howlett, A.C. Determination and characterization of a cannabinoid receptor in rat brain. Mol. Pharmacol., 1988, 34(5), 605-613.
[PMID: 2848184]
[28]
Melck, D.; Di Marzo, V.; Bisogno, T.; De Petrocellis, L.; Martin, B.R. Cannabimimetic fatty acid derivatives: The anandamide family and other endocannabinoids. Curr. Med. Chem., 1999, 6(8), 721-744.
[http://dx.doi.org/10.2174/0929867306666220401141630] [PMID: 10469888]
[29]
Esposito, G.; Izzo, A.A.; Di Rosa, M.; Iuvone, T. Selective cannabinoid CB1 receptor-mediated inhibition of inducible nitric oxide synthase protein expression in C6 rat glioma cells. J. Neurochem., 2001, 78(4), 835-841.
[http://dx.doi.org/10.1046/j.1471-4159.2001.00465.x] [PMID: 11520904]
[30]
Di Marzo, V.; Bisogno, T.; De Petrocellis, L.; Brandi, I.; Jefferson, R.G.; Winckler, R.L.; Davis, J.B.; Dasse, O.; Mahadevan, A.; Razdan, R.K.; Martin, B.R. Highly selective CB(1) cannabinoid receptor ligands and novel CB(1)/VR(1) vanilloid receptor “hybrid” ligands. Biochem. Biophys. Res. Commun., 2001, 281(2), 444-451.
[http://dx.doi.org/10.1006/bbrc.2001.4354] [PMID: 11181068]
[31]
Chiurchiù, V.; van der Stelt, M.; Centonze, D.; Maccarrone, M. The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases. Prog. Neurobiol., 2018, 160, 82-100.
[http://dx.doi.org/10.1016/j.pneurobio.2017.10.007] [PMID: 29097192]
[32]
Martin, B.R.; Beletskaya, I.; Patrick, G.; Jefferson, R.; Winckler, R.; Deutsch, D.G.; Di Marzo, V.; Dasse, O.; Mahadevan, A.; Razdan, R.K. Cannabinoid properties of methylfluorophosphonate analogs. J. Pharmacol. Exp. Ther., 2000, 294(3), 1209-1218.
[PMID: 10945879]
[33]
Navarro, M.; Hernández, E.; Muñoz, R.M.; del Arco, I.; Villanúa, M.A.; Carrera, M.R.A.; Rodríguez de Fonseca, F. Acute administration of the CB1 cannabinoid receptor antagonist SR 141716A induces anxiety-like responses in the rat. Neuroreport, 1997, 8(2), 491-496.
[http://dx.doi.org/10.1097/00001756-199701200-00023] [PMID: 9080435]
[34]
Malamas, M.S.; Raghav, J.G.; Ma, X.; Honrao, C.; Wood, J.T.; Benchama, O.; Zhou, H.; Mallipeddi, S.; Makriyannis, A. Oximes short-acting CB1 receptor agonists. Bioorg. Med. Chem., 2018, 26(18), 4963-4970.
[http://dx.doi.org/10.1016/j.bmc.2018.08.003] [PMID: 30122284]
[35]
Monory, K.; Tzavara, E.T.; Lexime, J.; Ledent, C.; Parmentier, M.; Borsodi, A.; Hanoune, J. Novel, not adenylyl cyclase-coupled cannabinoid binding site in cerebellum of mice. Biochem. Biophys. Res. Commun., 2002, 292(1), 231-235.
[http://dx.doi.org/10.1006/bbrc.2002.6635] [PMID: 11890697]
[36]
Straiker, A.; Wager-Miller, J.; Hutchens, J.; Mackie, K. Differential signalling in human cannabinoid CB1 receptors and their splice variants in autaptic hippocampal neurones. Br. J. Pharmacol., 2012, 165(8), 2660-2671.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01744.x] [PMID: 22014238]
[37]
Felder, C.C.; Veluz, J.S.; Williams, H.L.; Briley, E.M.; Matsuda, L.A. Cannabinoid agonists stimulate both receptor- and non-receptor-mediated signal transduction pathways in cells transfected with and expressing cannabinoid receptor clones. Mol. Pharmacol., 1992, 42(5), 838-845.
[PMID: 1331766]
[38]
Insel, T.R. Rethinking schizophrenia. Nature, 2010, 468(7321), 187-193.
[http://dx.doi.org/10.1038/nature09552] [PMID: 21068826]
[39]
Kumar, K.K. Structure of a signaling cannabinoid receptor 1-G protein complex. Cell, 2019, 176(3), 448-458.e12.
[http://dx.doi.org/10.1016/j.cell.2018.11.040] [PMID: 30639101]
[40]
Nguyen, T.; Thomas, B.F.; Zhang, Y. Overcoming the psychiatric side effects of the cannabinoid CB1 receptor antagonists: current approaches for therapeutics development. Curr. Top. Med. Chem., 2019, 19(16), 1418-1435.
[http://dx.doi.org/10.2174/1568026619666190708164841] [PMID: 31284863]
[41]
Showalter, V.M.; Compton, D.R.; Martin, B.R.; Abood, M.E. Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): Identification of cannabinoid receptor subtype selective ligands. J. Pharmacol. Exp. Ther., 1996, 278(3), 989-999.
[PMID: 8819477]
[42]
Lan, R.; Lu, Q.; Fan, P.; Gatley, J.; Volkow, N.D.; Fernando, S.R.; Pertwee, R.; Makriyannis, A. Design and synthesis of the CB1 selective cannabinoid antagonist AM281: A potential human SPECT ligand. AAPS PharmSci, 1999, 1(2), 39-45.
[http://dx.doi.org/10.1208/ps010204] [PMID: 11741201]
[43]
Hollinshead, S.P.; Tidwell, M.W.; Palmer, J.; Guidetti, R.; Sanderson, A.; Johnson, M.P.; Chambers, M.G.; Oskins, J.; Stratford, R.; Astles, P.C. Selective cannabinoid receptor type 2 (CB2) agonists: Optimization of a series of purines leading to the identification of a clinical candidate for the treatment of osteoarthritic pain. J. Med. Chem., 2013, 56(14), 5722-5733.
[http://dx.doi.org/10.1021/jm400305d] [PMID: 23795771]
[44]
Manera, C.; Saccomanni, G.; Malfitano, A.M.; Bertini, S.; Castelli, F.; Laezza, C.; Ligresti, A.; Lucchesi, V.; Tuccinardi, T.; Rizzolio, F.; Bifulco, M.; Di Marzo, V.; Giordano, A.; Macchia, M.; Martinelli, A. Rational design, synthesis and anti-proliferative properties of new CB2 selective cannabinoid receptor ligands: An investigation of the 1,8-naphthyridin-2(1H)-one scaffold. Eur. J. Med. Chem., 2012, 52, 284-294.
[http://dx.doi.org/10.1016/j.ejmech.2012.03.031] [PMID: 22483967]
[45]
Cabral, G.A.; Marciano-Cabral, F. Cannabinoid receptors in microglia of the central nervous system: Immune functional relevance. J. Leukoc. Biol., 2005, 78(6), 1192-1197.
[http://dx.doi.org/10.1189/jlb.0405216] [PMID: 16204639]
[46]
Stempel, A.V.; Stumpf, A.; Zhang, H.Y. Özdoğan, T.; Pannasch, U.; Theis, A.K.; Otte, D.M.; Wojtalla, A.; Rácz, I.; Ponomarenko, A.; Xi, Z.X.; Zimmer, A.; Schmitz, D. Cannabinoid type 2 receptors mediate a cell type-specific plasticity in the hippocampus. Neuron, 2016, 90(4), 795-809.
[http://dx.doi.org/10.1016/j.neuron.2016.03.034] [PMID: 27133464]
[47]
Rempel, V.; Volz, N.; Hinz, S.; Karcz, T.; Meliciani, I.; Nieger, M.; Wenzel, W.; Bräse, S.; Müller, C.E. 7-Alkyl-3-benzylcoumarins: A versatile scaffold for the development of potent and selective cannabinoid receptor agonists and antagonists. J. Med. Chem., 2012, 55(18), 7967-7977.
[http://dx.doi.org/10.1021/jm3008213] [PMID: 22916707]
[48]
Joshi, N.; Onaivi, E.S. Endocannabinoid system components: overview and tissue distribution; Recent Advances in Cannabinoid Physiology and Pathology, 2019, pp. 1-12.
[49]
Jordan, C.J.; Xi, Z.X. Progress in brain cannabinoid CB2 receptor research: From genes to behavior. Neurosci. Biobehav. Rev., 2019, 98, 208-220.
[http://dx.doi.org/10.1016/j.neubiorev.2018.12.026] [PMID: 30611802]
[50]
Benito, C.; Tolón, R.M.; Pazos, M.R.; Núñez, E.; Castillo, A.I.; Romero, J. Cannabinoid CB 2 receptors in human brain inflammation. Br. J. Pharmacol., 2008, 153(2), 277-285.
[http://dx.doi.org/10.1038/sj.bjp.0707505] [PMID: 17934510]
[51]
Adel, Y.; Alexander, S.P. Neuromolecular mechanisms of cannabis action. In: Cannabinoids and Neuropsychiatric Disorders. Advances in Experimental Medicine and Biology; Murillo-Rodriguez, E.; Pandi-Perumal, S.R.; Monti, J.M., Eds.; , 2021; p. 1264.
[http://dx.doi.org/10.1007/978-3-030-57369-0_2]
[52]
Leleu-Chavain, N.; Body-Malapel, M.; Spencer, J.; Chavatte, P.; Desreumaux, P.; Millet, R. Recent advances in the development of selective CB(2) agonists as promising anti-inflammatory agents. Curr. Med. Chem., 2012, 19(21), 3457-3474.
[http://dx.doi.org/10.2174/092986712801323207] [PMID: 22709008]
[53]
Gertsch, J. Antiinflammatory cannabinoids in diet – towards a better understanding of CB2 receptor action? Commun. Integr. Biol., 2008, 1(1), 26-28.
[http://dx.doi.org/10.4161/cib.1.1.6568] [PMID: 19704783]
[54]
Diaz, P.; Phatak, S.S.; Xu, J.; Fronczek, F.R.; Astruc-Diaz, F.; Thompson, C.M.; Cavasotto, C.N.; Naguib, M. 2,3-Dihydro-1-benzofuran derivatives as a series of potent selective cannabinoid receptor 2 agonists: Design, synthesis, and binding mode prediction through ligand-steered modeling. ChemMedChem, 2009, 4(10), 1615-1629.
[http://dx.doi.org/10.1002/cmdc.200900226] [PMID: 19637157]
[55]
Xin, Q.; Xu, F.; Taylor, D.H.; Zhao, J.; Wu, J. The impact of cannabinoid type 2 receptors (CB2Rs) in neuroprotection against neurological disorders. Acta Pharmacol. Sin., 2020, 41(12), 1507-1518.
[http://dx.doi.org/10.1038/s41401-020-00530-2] [PMID: 33024239]
[56]
Li, X.; Tian, H.; Kiran, V. Crystal structure of the human cannabinoid receptor CB2. Cell, 2019, 176(3), 459-467.e13.
[http://dx.doi.org/10.1016/j.cell.2018.12.011]
[57]
Krishna Deepak, R.N.V.; Verma, R.K.; Hartono, Y.D.; Yew, W.S.; Fan, H. Recent advances in structure, function, and pharmacology of class a lipid GPCRs: Opportunities and challenges for drug discovery. Pharmaceuticals, 2021, 15(1), 12.
[http://dx.doi.org/10.3390/ph15010012] [PMID: 35056070]
[58]
Shahbazi, F.; Grandi, V.; Banerjee, A.; Trant, J.F. Cannabinoids and cannabinoid receptors: The story so far. iScience, 2020, 23(7), 101301.
[http://dx.doi.org/10.1016/j.isci.2020.101301] [PMID: 32629422]
[59]
Rodríguez de Fonseca, F.; Del Arco, I.; Bermudez-Silva, F.J.; Bilbao, A.; Cippitelli, A.; Navarro, M. The endocannabinoid system: Physiology and pharmacology. Alcohol Alcohol., 2005, 40(1), 2-14.
[http://dx.doi.org/10.1093/alcalc/agh110] [PMID: 15550444]
[60]
Raymon, L.P.; Walls, H. Pharmacology of cannabinoids; Marijuana and the Cannabinoids, 2007, pp. 97-123.
[61]
Richard, D.; Guesdon, B.; Timofeeva, E. The brain endocannabinoid system in the regulation of energy balance. Best Pract. Res. Clin. Endocrinol. Metab., 2009, 23(1), 17-32.
[http://dx.doi.org/10.1016/j.beem.2008.10.007] [PMID: 19285258]
[62]
Ross, R. Allosterism and cannabinoid CB1 receptors: The shape of things to come. Trends Pharmacol. Sci., 2007, 28(11), 567-572.
[http://dx.doi.org/10.1016/j.tips.2007.10.006] [PMID: 18029031]
[63]
Chung, H.; Fierro, A.; Pessoa-Mahana, C.D. Cannabidiol binding and negative allosteric modulation at the cannabinoid type 1 receptor in the presence of delta-9-tetrahydrocannabinol: An In Silico study. PLoS One, 2019, 14(7), e0220025.
[http://dx.doi.org/10.1371/journal.pone.0220025] [PMID: 31335889]
[64]
Corradi, V.; Sejdiu, B.I.; Mesa-Galloso, H.; Abdizadeh, H.; Noskov, S.Y.; Marrink, S.J.; Tieleman, D.P. Emerging diversity in lipid–protein interactions. Chem. Rev., 2019, 119(9), 5775-5848.
[http://dx.doi.org/10.1021/acs.chemrev.8b00451] [PMID: 30758191]
[65]
Massi, P.; Vaccani, A.; Parolaro, D. Cannabinoids, immune system and cytokine network. Curr. Pharm. Des., 2006, 12(24), 3135-3146.
[http://dx.doi.org/10.2174/138161206777947425] [PMID: 16918439]
[66]
Pertwee, R.G. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol. Ther., 1997, 74(2), 129-180.
[http://dx.doi.org/10.1016/S0163-7258(97)82001-3] [PMID: 9336020]
[67]
Reggio, P.H. Toward the design of cannabinoid CB1 receptor inverse agonists and neutral antagonists. Drug Dev. Res., 2009, 70(8), 585-600.
[http://dx.doi.org/10.1002/ddr.20337]
[68]
Cheng, Y.; Hitchcock, S.A. Targeting cannabinoid agonists for inflammatory and neuropathic pain. Expert Opin. Investig. Drugs, 2007, 16(7), 951-965.
[http://dx.doi.org/10.1517/13543784.16.7.951] [PMID: 17594182]
[69]
Pertwee, R.G. The pharmacology of cannabinoid receptors and their ligands: An overview. Int. J. Obes., 2006, 30(S1), S13-S18.
[http://dx.doi.org/10.1038/sj.ijo.0803272] [PMID: 16570099]
[70]
Gaoni, Y.; Mechoulam, R. Isolation, structure, and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc., 1964, 86(8), 1646-1647.
[http://dx.doi.org/10.1021/ja01062a046]
[71]
Hensen, B. Cannabinoid therapeutics: High hopes for the future. Drug Discov. Today, 2005, 10(7), 459-462.
[http://dx.doi.org/10.1016/S1359-6446(05)03417-3] [PMID: 15809190]
[72]
Manzanares, J.; Julian, M.; Carrascosa, A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr. Neuropharmacol., 2006, 4(3), 239-257.
[http://dx.doi.org/10.2174/157015906778019527] [PMID: 18615144]
[73]
Rinaldi-Carmona, M.; Barth, F.; Héaulme, M.; Shire, D.; Calandra, B.; Congy, C.; Martinez, S.; Maruani, J.; Néliat, G.; Caput, D.; Ferrara, P.; Soubrié, P.; Brelière, J.C.; Le Fur, G. SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett., 1994, 350(2-3), 240-244.
[http://dx.doi.org/10.1016/0014-5793(94)00773-X] [PMID: 8070571]
[74]
Lin, L.S.; Lanza, T.J., Jr; Jewell, J.P.; Liu, P.; Shah, S.K.; Qi, H.; Tong, X.; Wang, J.; Xu, S.S.; Fong, T.M.; Shen, C.P.; Lao, J.; Xiao, J.C.; Shearman, L.P.; Stribling, D.S.; Rosko, K.; Strack, A.; Marsh, D.J.; Feng, Y.; Kumar, S.; Samuel, K.; Yin, W.; Van der Ploeg, L.H.T.; Goulet, M.T.; Hagmann, W.K. Discovery of N -[(1 S, 2 S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2- [5-(trifluoromethyl)pyridin-2-yl]oxypropanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity. J. Med. Chem., 2006, 49(26), 7584-7587.
[http://dx.doi.org/10.1021/jm060996+] [PMID: 17181138]
[75]
Gao, H.M.; Hong, J.S. Why neurodegenerative diseases are progressive: Uncontrolled inflammation drives disease progression. Trends Immunol., 2008, 29(8), 357-365.
[http://dx.doi.org/10.1016/j.it.2008.05.002] [PMID: 18599350]
[76]
Mingle, D.; Ospanov, M.; Radwan, M.O.; Ashpole, N.; Otsuka, M.; Ross, S.A.; Walker, L.A.; Shilabin, A.G.; Ibrahim, M.A. First in class (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs as selective CB2 modulators targeting neurodegenerative disorders. Med. Chem. Res., 2021, 30(1), 98-108.
[http://dx.doi.org/10.1007/s00044-020-02640-2] [PMID: 33776384]
[77]
González-Naranjo, P.; Pérez-Macias, N.; Campillo, N.E.; Pérez, C.; Arán, V.J.; Girón, R.; Sánchez-Robles, E.; Martín, M.I.; Gómez-Cañas, M.; García-Arencibia, M.; Fernández-Ruiz, J.; Páez, J.A. Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer’s disease. Eur. J. Med. Chem., 2014, 73, 56-72.
[http://dx.doi.org/10.1016/j.ejmech.2013.11.026] [PMID: 24378710]
[78]
Montanari, S.; Mahmoud, A.M.; Pruccoli, L.; Rabbito, A.; Naldi, M.; Petralla, S.; Moraleda, I.; Bartolini, M.; Monti, B.; Iriepa, I.; Belluti, F.; Gobbi, S.; Di Marzo, V.; Bisi, A.; Tarozzi, A.; Ligresti, A.; Rampa, A. Discovery of novel benzofuran-based compounds with neuroprotective and immunomodulatory properties for Alzheimer’s disease treatment. Eur. J. Med. Chem., 2019, 178, 243-258.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.080] [PMID: 31185414]
[79]
Röver, S.; Andjelkovic, M.; Bénardeau, A.; Chaput, E.; Guba, W.; Hebeisen, P.; Mohr, S.; Nettekoven, M.; Obst, U.; Richter, W.F.; Ullmer, C.; Waldmeier, P.; Wright, M.B. 6-Alkoxy-5-aryl-3-pyridinecarboxamides, a new series of bioavailable cannabinoid receptor type 1 (CB1) antagonists including peripherally selective compounds. J. Med. Chem., 2013, 56(24), 9874-9896.
[http://dx.doi.org/10.1021/jm4010708] [PMID: 24175572]
[80]
Pandey, P.; Roy, K.; Liu, H.; Ma, G.; Pettaway, S.; Alsharif, W.; Gadepalli, R.; Rimoldi, J.; McCurdy, C.; Cutler, S.; Doerksen, R. Structure-based identification of potent natural product chemotypes as cannabinoid receptor 1 inverse agonists. Molecules, 2018, 23(10), 2630.
[http://dx.doi.org/10.3390/molecules23102630] [PMID: 30322136]
[81]
Zhang, Y.M.; Greco, M.N.; Macielag, M.J.; Teleha, C.A.; DesJarlais, R.L.; Tang, Y.; Ho, G.; Hou, C.; Chen, C.; Zhao, S.; Kauffman, J.; Camacho, R.; Qi, J.; Murray, W.; Demarest, K.; Leonard, J. 6-Benzhydryl-4-amino-quinolin-2-ones as potent cannabinoid type 1 (CB1) receptor inverse agonists and chemical modifications for peripheral selectivity. J. Med. Chem., 2018, 61(22), 10276-10298.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01467] [PMID: 30339387]
[82]
Chorvat, R.J.; Berbaum, J.; Seriacki, K.; McElroy, J.F. JD-5006 and JD-5037: Peripherally restricted (PR) cannabinoid-1 receptor blockers related to SLV-319 (Ibipinabant) as metabolic disorder therapeutics devoid of CNS liabilities. Bioorg. Med. Chem. Lett., 2012, 22(19), 6173-6180.
[http://dx.doi.org/10.1016/j.bmcl.2012.08.004] [PMID: 22959249]
[83]
Heilig, M.; Egli, M. Pharmacological treatment of alcohol dependence: Target symptoms and target mechanisms. Pharmacol. Ther., 2006, 111(3), 855-876.
[http://dx.doi.org/10.1016/j.pharmthera.2006.02.001] [PMID: 16545872]
[84]
Lazary, J.; Juhasz, G.; Hunyady, L.; Bagdy, G. Personalized medicine can pave the way for the safe use of CB1 receptor antagonists. Trends Pharmacol. Sci., 2011, 32(5), 270-280.
[http://dx.doi.org/10.1016/j.tips.2011.02.013] [PMID: 21497918]
[85]
Fulp, A.; Zhang, Y.; Bortoff, K.; Seltzman, H.; Snyder, R.; Wiethe, R.; Amato, G.; Maitra, R. Pyrazole antagonists of the CB1 receptor with reduced brain penetration. Bioorg. Med. Chem., 2016, 24(5), 1063-1070.
[http://dx.doi.org/10.1016/j.bmc.2016.01.033] [PMID: 26827137]
[86]
Tu, G.; Xiong, F.; Huang, H.; Kuang, B.; Li, S. Design, synthesis and biological evaluation of CB1 cannabinoid receptor ligands derived from the 1,5-diarylpyrazole scaffold. J. Enzyme Inhib. Med. Chem., 2011, 26(2), 222-230.
[http://dx.doi.org/10.3109/14756366.2010.491794] [PMID: 20565336]
[87]
Chang, C.P.; Wu, C.H.; Song, J.S.; Chou, M.C.; Wong, Y.C.; Lin, Y.; Yeh, T.K.; Sadani, A.A.; Ou, M.H.; Chen, K.H.; Chen, P.H.; Kuo, P.C.; Tseng, C.T.; Chang, K.H.; Tseng, S.L.; Chao, Y.S.; Hung, M.S.; Shia, K.S. Discovery of 1-(2,4-Dichlorophenyl)- N-(piperidin-1-yl)-4-((pyrrolidine-1-sulfonamido)methyl)-5-(5-((4-(trifluoromethyl)phenyl)ethynyl)thiophene-2-yl)-1 H -pyrazole-3-carboxamide as a novel peripherally restricted cannabinoid-1 receptor antagonist with significant weight-loss efficacy in diet-induced obese mice. J. Med. Chem., 2013, 56(24), 9920-9933.
[http://dx.doi.org/10.1021/jm401158e] [PMID: 24224693]
[88]
Murineddu, G.; Asproni, B.; Corona, P.; Piras, S.; Lazzari, P.; Ruiu, S.; Legnani, L.; Toma, L.; Pinna, G.A. Development of oxygen-bridged pyrazole-based structures as cannabinoid receptor 1 ligands. Molecules, 2019, 24(9), 1656.
[http://dx.doi.org/10.3390/molecules24091656] [PMID: 31035548]
[89]
Sharma, M.K.; Murumkar, P.R.; Giridhar, R.; Yadav, M.R. Exploring structural requirements for peripherally acting 1,5-diaryl pyrazole-containing cannabinoid 1 receptor antagonists for the treatment of obesity. Mol. Divers., 2015, 19(4), 871-893.
[http://dx.doi.org/10.1007/s11030-015-9611-5] [PMID: 26183840]
[90]
Sharma, M.K.; Machhi, J.; Murumkar, P.; Yadav, M.R. New role of phenothiazine derivatives as peripherally acting CB1 receptor antagonizing anti-obesity agents. Sci. Rep., 2018, 8(1), 1650.
[http://dx.doi.org/10.1038/s41598-018-20078-w] [PMID: 29374224]
[91]
Sarnataro, D.; Pisanti, S.; Santoro, A.; Gazzerro, P.; Malfitano, A.M.; Laezza, C.; Bifulco, M. The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits human breast cancer cell proliferation through a lipid raft-mediated mechanism. Mol. Pharmacol., 2006, 70(4), 1298-1306.
[http://dx.doi.org/10.1124/mol.106.025601] [PMID: 16822929]
[92]
Kogan, N.M.; Rabinowitz, R.; Levi, P.; Gibson, D.; Sandor, P.; Schlesinger, M.; Mechoulam, R. Synthesis and antitumor activity of quinonoid derivatives of cannabinoids. J. Med. Chem., 2004, 47(15), 3800-3806.
[http://dx.doi.org/10.1021/jm040042o] [PMID: 15239658]
[93]
Morales, P.; Vara, D.; Goméz-Cañas, M.; Zúñiga, M.C.; Olea-Azar, C.; Goya, P.; Fernández-Ruiz, J.; Díaz-Laviada, I.; Jagerovic, N. Synthetic cannabinoid quinones: Preparation, in vitro antiproliferative effects and in vivo prostate antitumor activity. Eur. J. Med. Chem., 2013, 70, 111-119.
[http://dx.doi.org/10.1016/j.ejmech.2013.09.043] [PMID: 24141201]
[94]
Morales, P.; Blasco-Benito, S.; Andradas, C.; Gómez-Cañas, M.; Flores, J.M.; Goya, P.; Fernández-Ruiz, J.; Sánchez, C.; Jagerovic, N. Selective, nontoxic CB(2) cannabinoid o-quinone with in vivo activity against triple-negative breast cancer. J. Med. Chem., 2015, 58(5), 2256-2264.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00078] [PMID: 25671648]
[95]
Manera, C.; Malfitano, A.M.; Parkkari, T.; Lucchesi, V.; Carpi, S.; Fogli, S.; Bertini, S.; Laezza, C.; Ligresti, A.; Saccomanni, G.; Savinainen, J.R.; Ciaglia, E.; Pisanti, S.; Gazzerro, P.; Di Marzo, V.; Nieri, P.; Macchia, M.; Bifulco, M. New quinolone- and 1,8-naphthyridine-3-carboxamides as selective CB2 receptor agonists with anticancer and immuno–modulatory activity. Eur. J. Med. Chem., 2015, 97, 10-18.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.034] [PMID: 25935384]
[96]
Sathynathan, C.V.; Raman, L.S.; Vajiravelu, S.; Kumar, T.D.; Panchatcharam, T.S.; Narasimhan, G.; Doss, G.C.P.; Krishnan, M.E.G. 3-Hydroxypropane-1,2-Diyl Dipalmitoleate—a natural compound with dual Roles (CB1 Agonist/FAAH1 Blocker) in inhibiting ovarian cancer cell line. Pharmaceuticals, 2021, 14(3), 255.
[http://dx.doi.org/10.3390/ph14030255] [PMID: 33809034]
[97]
Youssif, B.G.M.; Mohamed, A.M.; Osman, E.E.A.; Abou-Ghadir, O.F.; Elnaggar, D.H.; Abdelrahman, M.H.; Treamblu, L.; Gomaa, H.A.M. 5-Chlorobenzofuran-2-carboxamides: From allosteric CB1 modulators to potential apoptotic antitumor agents. Eur. J. Med. Chem., 2019, 177, 1-11.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.040] [PMID: 31128433]
[98]
Mugnaini, C.; Rabbito, A.; Brizzi, A.; Palombi, N.; Petrosino, S.; Verde, R.; Di Marzo, V.; Ligresti, A.; Corelli, F. Synthesis of novel 2-(1-adamantanylcarboxamido)thiophene derivatives. Selective cannabinoid type 2 (CB2) receptor agonists as potential agents for the treatment of skin inflammatory disease. Eur. J. Med. Chem., 2019, 161, 239-251.
[http://dx.doi.org/10.1016/j.ejmech.2018.09.070] [PMID: 30359820]
[99]
Schoeder, C.T. Kaleta, M.; Mahardhika, A.B.; Olejarz-Maciej, A.; Łażewska, D.; Kieć-Kononowicz, K.; Müller, C.E. Structure-activity relationships of imidazothiazinones and analogs as antagonists of the cannabinoid-activated orphan G protein-coupled receptor GPR18. Eur. J. Med. Chem., 2018, 155, 381-397.
[http://dx.doi.org/10.1016/j.ejmech.2018.05.050] [PMID: 29902723]
[100]
Li, J.; Ji, J.; Xu, R.; Li, Z. Indole compounds with N -ethyl morpholine moieties as CB2 receptor agonists for anti-inflammatory management of pain: Synthesis and biological evaluation. MedChemComm, 2019, 10(11), 1935-1947.
[http://dx.doi.org/10.1039/C9MD00173E] [PMID: 32952995]
[101]
Ghonim, A.E.; Ligresti, A.; Rabbito, A.; Mahmoud, A.M.; Di Marzo, V.; Osman, N.A.; Abadi, A.H. Structure-activity relationships of thiazole and benzothiazole derivatives as selective cannabinoid CB2 agonists with in vivo anti-inflammatory properties. Eur. J. Med. Chem., 2019, 180, 154-170.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.002] [PMID: 31302448]
[102]
Wadea, N.E.; Issac, M.M.; Osman, N.A.; Abadi, A.H. Benzofuran and pyrrole derivatives as cannabinoid receptor modulators with in vivo efficacy against ulcerative colitis. Future Med. Chem., 2019, 11(24), 3139-3159.
[http://dx.doi.org/10.4155/fmc-2019-0172] [PMID: 31838898]
[103]
Amato, G.S.; Manke, A.; Harris, D.L.; Wiethe, R.W.; Vasukuttan, V.; Snyder, R.W.; Lefever, T.W.; Cortes, R.; Zhang, Y.; Wang, S.; Runyon, S.P.; Maitra, R. Blocking alcoholic steatosis in mice with a peripherally restricted purine antagonist of the type 1 cannabinoid receptor. J. Med. Chem., 2018, 61(10), 4370-4385.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01820] [PMID: 29688015]
[104]
Compton, D.R.; Rice, K.C.; De Costa, B.R.; Razdan, R.K.; Melvin, L.S.; Johnson, M.R.; Martin, B.R. Cannabinoid structure-activity relationships: correlation of receptor binding and in vivo activities. J. Pharmacol. Exp. Ther., 1993, 265(1), 218-226.
[PMID: 8474008]
[105]
Atwood, B.K.; Mackie, K. CB2: A cannabinoid receptor with an identity crisis. Br. J. Pharmacol., 2010, 160(3), 467-479.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00729.x] [PMID: 20590558]
[106]
Ragusa, G.; Gómez-Cañas, M.; Morales, P.; Rodríguez-Cueto, C.; Pazos, M.R.; Asproni, B.; Cichero, E.; Fossa, P.; Pinna, G.A.; Jagerovic, N.; Fernández-Ruiz, J.; Murineddu, G. New pyridazinone-4-carboxamides as new cannabinoid receptor type-2 inverse agonists: Synthesis, pharmacological data and molecular docking. Eur. J. Med. Chem., 2017, 127, 398-412.
[http://dx.doi.org/10.1016/j.ejmech.2017.01.002] [PMID: 28088085]
[107]
Christensen, R.; Kristensen, P.K.; Bartels, E.M.; Bliddal, H.; Astrup, A. Efficacy and safety of the weight-loss drug rimonabant: A meta-analysis of randomised trials. Lancet, 2007, 370(9600), 1706-1713.
[http://dx.doi.org/10.1016/S0140-6736(07)61721-8] [PMID: 18022033]
[108]
Varga, B.; Kassai, F.; Szabó, G.; Kovács, P.; Fischer, J.; Gyertyán, I. Pharmacological comparison of traditional and non-traditional cannabinoid receptor 1 blockers in rodent models in vivo. Pharmacol. Biochem. Behav., 2017, 159, 24-35.
[http://dx.doi.org/10.1016/j.pbb.2017.06.012] [PMID: 28666894]
[109]
Matthews, J.M.; McNally, J.J.; Connolly, P.J.; Xia, M.; Zhu, B.; Black, S.; Chen, C.; Hou, C.; Liang, Y.; Tang, Y.; Macielag, M.J. Tetrahydroindazole derivatives as potent and peripherally selective cannabinoid-1 (CB1) receptor inverse agonists. Bioorg. Med. Chem. Lett., 2016, 26(21), 5346-5349.
[http://dx.doi.org/10.1016/j.bmcl.2016.09.025] [PMID: 27671496]
[110]
Griffith, D.A.; Hadcock, J.R.; Black, S.C.; Iredale, P.A.; Carpino, P.A.; DaSilva-Jardine, P.; Day, R.; DiBrino, J.; Dow, R.L.; Landis, M.S.; O’Connor, R.E.; Scott, D.O. Discovery of 1-[9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylaminopiperidine-4-carboxylic acid amide hydrochloride (CP-945,598), a novel, potent, and selective cannabinoid type 1 receptor antagonist. J. Med. Chem., 2009, 52(2), 234-237.
[http://dx.doi.org/10.1021/jm8012932] [PMID: 19102698]
[111]
Amato, G.S.; Manke, A.; Vasukuttan, V.; Wiethe, R.W.; Snyder, R.W.; Runyon, S.P.; Maitra, R. Synthesis and pharmacological characterization of functionalized 6-piperazin-1-yl-purines as cannabinoid receptor 1 (CB1) inverse agonists. Bioorg. Med. Chem., 2018, 26(15), 4518-4531.
[http://dx.doi.org/10.1016/j.bmc.2018.07.043] [PMID: 30077609]
[112]
McGolrick, D.; Frey, N. Nabilone for Chronic Pain Management: A Review of Clinical Effectiveness and Guidelines – An Update. In: CADTH Rapid Response Reports; Canadian Agency for Drugs and Technologies in Health: Ottawa (ON), 2018.
[PMID: 30896900]
[113]
Penthala, N.R.; Shoeib, A.; Dachavaram, S.S.; Cabanlong, C.V.; Yang, J.; Zhan, C.G.; Prather, P.L.; Crooks, P.A. 7-Azaindolequinuclidinones (7-AIQD): A novel class of cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor ligands. Bioorg. Med. Chem. Lett., 2020, 30(22), 127501.
[http://dx.doi.org/10.1016/j.bmcl.2020.127501] [PMID: 32882418]
[114]
Cassano, T.; Villani, R.; Pace, L.; Carbone, A.; Bukke, V.N.; Orkisz, S.; Avolio, C.; Serviddio, G. From cannabis sativa to cannabidiol: Promising therapeutic candidate for the treatment of neurodegenerative diseases. Front. Pharmacol., 2020, 11, 124.
[http://dx.doi.org/10.3389/fphar.2020.00124] [PMID: 32210795]
[115]
Oz, M. Receptor-independent effects of endocannabinoids on ion channels. Curr. Pharm. Des., 2006, 12(2), 227-239.
[http://dx.doi.org/10.2174/138161206775193073] [PMID: 16454739]
[116]
Aly, E. Khajah, M.A.; Masocha, W. β-Caryophyllene, a CB2-receptor-selective phytocannabinoid, suppresses mechanical allodynia in a mouse model of antiretroviral-induced neuropathic pain. Molecules, 2019, 25(1), 106.
[http://dx.doi.org/10.3390/molecules25010106] [PMID: 31892132]
[117]
Shi, Y.; Duan, Y.H.; Ji, Y.Y.; Wang, Z.L.; Wu, Y.R.; Gunosewoyo, H.; Xie, X.Y.; Chen, J.Z.; Yang, F.; Li, J.; Tang, J.; Xie, X.; Yu, L.F. Amidoalkylindoles as potent and selective cannabinoid type 2 receptor agonists with in vivo efficacy in a mouse model of multiple sclerosis. J. Med. Chem., 2017, 60(16), 7067-7083.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00724] [PMID: 28726401]
[118]
Bermudez-Silva, F.J.; Viveros, M.P.; McPartland, J.M.; Rodriguez de Fonseca, F. The endocannabinoid system, eating behavior and energy homeostasis: The end or a new beginning? Pharmacol. Biochem. Behav., 2010, 95(4), 375-382.
[http://dx.doi.org/10.1016/j.pbb.2010.03.012] [PMID: 20347862]
[119]
Espinosa-Bustos, C.; Lagos, C.F.; Romero-Parra, J.; Zárate, A.M.; Mella-Raipán, J.; Pessoa-Mahana, H.; Recabarren-Gajardo, G.; Iturriaga-Vásquez, P.; Tapia, R.A.; Pessoa-Mahana, C.D. Design, synthesis, biological evaluation and binding mode modeling of benzimidazole derivatives targeting the cannabinoid receptor type 1. Arch. Pharm., 2015, 348(2), 81-88.
[http://dx.doi.org/10.1002/ardp.201400201] [PMID: 25641513]
[120]
Dhopeshwarkar, A.; Mackie, K. Functional selectivity of CB2 cannabinoid receptor ligands at a canonical and noncanonical pathway. J. Pharmacol. Exp. Ther., 2016, 358(2), 342-351.
[http://dx.doi.org/10.1124/jpet.116.232561] [PMID: 27194477]
[121]
Li, A.L.; Lin, X.; Dhopeshwarkar, A.S.; Thomaz, A.C.; Carey, L.M.; Liu, Y.; Nikas, S.P.; Makriyannis, A.; Mackie, K.; Hohmann, A.G. Cannabinoid CB2 agonist AM1710 differentially suppresses distinct pathological pain states and attenuates morphine tolerance and withdrawal. Mol. Pharmacol., 2019, 95(2), 155-168.
[http://dx.doi.org/10.1124/mol.118.113233] [PMID: 30504240]
[122]
Alapafuja, S.O.; Nikas, S.P.; Ho, T.C.; Tong, F.; Benchama, O.; Makriyannis, A. Chain substituted cannabilactones with selectivity for the CB2 cannabinoid receptor. Molecules, 2019, 24(19), 3559.
[http://dx.doi.org/10.3390/molecules24193559] [PMID: 31581433]
[123]
Han, S.; Zhang, F.F.; Qian, H.Y.; Chen, L.L.; Pu, J.B.; Xie, X.; Chen, J.Z. Design, syntheses, structure–activity relationships and docking studies of coumarin derivatives as novel selective ligands for the CB2 receptor. Eur. J. Med. Chem., 2015, 93, 16-32.
[http://dx.doi.org/10.1016/j.ejmech.2015.01.054] [PMID: 25644673]
[124]
Odan, M.; Ishizuka, N.; Hiramatsu, Y.; Inagaki, M.; Hashizume, H.; Fujii, Y.; Mitsumori, S.; Morioka, Y.; Soga, M.; Deguchi, M.; Yasui, K.; Arimura, A. Discovery of S-777469: An orally available CB2 agonist as an antipruritic agent. Bioorg. Med. Chem. Lett., 2012, 22(8), 2803-2806.
[http://dx.doi.org/10.1016/j.bmcl.2012.02.072] [PMID: 22444677]
[125]
Han, S.; Zhang, F.F.; Xie, X.; Chen, J.Z. Design, synthesis, biological evaluation, and comparative docking study of 1,2,4-triazolones as CB1 receptor selective antagonists. Eur. J. Med. Chem., 2014, 74, 73-84.
[http://dx.doi.org/10.1016/j.ejmech.2013.12.018] [PMID: 24445310]
[126]
Singh, U.P.; Singh, N.P.; Singh, B.; Price, R.L.; Nagarkatti, M.; Nagarkatti, P.S. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10−/− mice by attenuating the activation of T cells and promoting their apoptosis. Toxicol. Appl. Pharmacol., 2012, 258(2), 256-267.
[http://dx.doi.org/10.1016/j.taap.2011.11.005] [PMID: 22119709]
[127]
Moir, M.; Lane, S.; Montgomery, A.P.; Hibbs, D.; Connor, M.; Kassiou, M. The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist. Eur. J. Med. Chem., 2021, 210, 113087.
[http://dx.doi.org/10.1016/j.ejmech.2020.113087] [PMID: 33321261]
[128]
Qian, H.Y.; Wang, Z.L.; Chen, L.L.; Pan, Y.L.; Xie, X.Y.; Xie, X.; Chen, J.Z. Design, synthesis, and SAR studies of heteroarylpyrimidines and heteroaryltriazines as CB 2 R ligands. ChemMedChem, 2018, 13(22), 2455-2463.
[http://dx.doi.org/10.1002/cmdc.201800541] [PMID: 30246417]

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