ACS Publications. Most Trusted. Most Cited. Most Read
My Activity

Cannabilactones: A Novel Class of CB2 Selective Agonists with Peripheral Analgesic Activity

View Author Information
Center for Drug Discovery, Northeastern University, 116 Mugar Hall, 360 Huntington Avenue, Boston, Massachusetts 02115-5000, Departments of Anesthesiology and Pharmacology, University of Arizona College of Medicine, 1501 North Campbell Avenue, Tucson, Arizona 85724-5114, Naval Research Laboratory, Code 6030, 4555 Overlook Avenue, Washington, DC 20375-5341, and Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vass. Constantinou, Athens 116-35 Greece
* To whom correspondence should be addressed Tel.: 1-617-373-4200 . Fax: 1-617-373-7493. E-mail: [email protected]
†Northeastern University.
‡University of Arizona College of Medicine.
§Naval Research Laboratory.
∥National Hellenic Research Foundation.
Cite this: J. Med. Chem. 2007, 50, 26, 6493–6500
Publication Date (Web):November 27, 2007
Copyright © 2007 American Chemical Society

    Article Views





    Other access options
    Supporting Info (1)»


    Abstract Image

    The identification of the CB2 cannabinoid receptor has provided a novel target for the development of therapeutically useful cannabinergic molecules. We have synthesized benzo[c]chromen-6-one analogs possessing high affinity and selectivity for this receptor. These novel compounds are structurally related to cannabinol (6,6,9-trimethyl-3-pentyl-6H-benzo[c]chromen-1-ol), a natural constituent of cannabis with modest CB2 selectivity. Key pharmacophoric features of the new selective agonists include a 3-(1′,1′-dimethylheptyl) side chain and a 6-oxo group on the cannabinoid tricyclic structure that characterizes this class of compounds as “cannabilactones.” Our results suggest that the six-membered lactone pharmacophore is critical for CB2 receptor selectivity. Optimal receptor subtype selectivity of 490-fold and subnanomolar affinity for the CB2 receptor is exhibited by a 9-hydroxyl analog 5 (AM1714), while the 9-methoxy analog 4b (AM1710) had a 54-fold CB2 selectivity. X-ray crystallography and molecular modeling show the cannabilactones to have a planar ring conformation. In vitro testing revealed that the novel compounds are CB2 agonists, while in vivo testing of cannabilactones 4b and 5 found them to possess potent peripheral analgesic activity.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.


    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    Supporting Information

    Jump To

    Elemental analyses data and X-ray diffraction data for 4a and 4b. This material is available free of charge via the Internet at .

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system:

    Cited By

    This article is cited by 81 publications.

    1. Pritam Roy, David G. Dennis, Mark D. Eschbach, Shravanthi D. Anand, Fengyun Xu, Jonathan Maturano, Judith Hellman, David Sarlah, Aditi Das. Metabolites of Cannabigerol Generated by Human Cytochrome P450s Are Bioactive. Biochemistry 2022, 61 (21) , 2398-2408.
    2. Shan Jiang, Christos Iliopoulos-Tsoutsouvas, Fei Tong, Christina A. Brust, Catherine M. Keenan, Jimit Girish Raghav, Tian Hua, Simiao Wu, Jo-Hao Ho, Yiran Wu, Travis W. Grim, Nikolai Zvonok, Ganesh A. Thakur, Zhi-Jie Liu, Keith A. Sharkey, Laura M. Bohn, Spyros P. Nikas, Alexandros Makriyannis. Novel Functionalized Cannabinoid Receptor Probes: Development of Exceptionally Potent Agonists. Journal of Medicinal Chemistry 2021, 64 (7) , 3870-3884.
    3. Thanh C. Ho, Naoyuki Shimada, Marcus A. Tius, Spyros P. Nikas, Wen Zhang, and Alexandros Makriyannis . C1′-Azacycloalkyl Hexahydrocannabinols. The Journal of Organic Chemistry 2017, 82 (15) , 7839-7849.
    4. Joydev K. Laha, Ketul V. Patel, and Sheetal Sharma . Palladium-Catalyzed Decarboxylative Ortho-Acylation of Tertiary Benzamides with Arylglyoxylic Acids. ACS Omega 2017, 2 (7) , 3806-3815.
    5. Dong-Dong Guo, Bin Li, Da-Yu Wang, Ya-Ru Gao, Shi-Huan Guo, Gao-Fei Pan, and Yong-Qiang Wang . Synthesis of 6H-Benzo[c]chromenes via Palladium-Catalyzed Intramolecular Dehydrogenative Coupling of Two Aryl C–H Bonds. Organic Letters 2017, 19 (4) , 798-801.
    6. Shashank Kulkarni, Spyros P. Nikas, Rishi Sharma, Shan Jiang, Carol A. Paronis, Michael Z. Leonard, Bin Zhang, Chandrashekhar Honrao, Srikrishnan Mallipeddi, Jimit Girish Raghav, Othman Benchama, Torbjörn U. C. Järbe, Jack Bergman, and Alexandros Makriyannis . Novel C-Ring-Hydroxy-Substituted Controlled Deactivation Cannabinergic Analogues. Journal of Medicinal Chemistry 2016, 59 (14) , 6903-6919.
    7. Pradeep Nareddy, Frank Jordan, Stacey E. Brenner-Moyer, and Michal Szostak . Ruthenium(II)-Catalyzed Regioselective C–H Arylation of Cyclic and N,N-Dialkyl Benzamides with Boronic Acids by Weak Coordination. ACS Catalysis 2016, 6 (7) , 4755-4759.
    8. Pushkar M. Kulkarni, Abhijit R. Kulkarni, Anisha Korde, Ritesh B. Tichkule, Robert B. Laprairie, Eileen M. Denovan-Wright, Han Zhou, David R. Janero, Nikolai Zvonok, Alexandros Makriyannis, Maria G. Cascio, Roger G. Pertwee, and Ganesh A. Thakur . Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s). Journal of Medicinal Chemistry 2016, 59 (1) , 44-60.
    9. Go Ogawa, Marcus A. Tius, Han Zhou, Spyros P. Nikas, Aneetha Halikhedkar, Srikrishnan Mallipeddi, and Alexandros Makriyannis . 3′-Functionalized Adamantyl Cannabinoid Receptor Probes. Journal of Medicinal Chemistry 2015, 58 (7) , 3104-3116.
    10. Spyros P. Nikas, Rishi Sharma, Carol A. Paronis, Shashank Kulkarni, Ganesh A. Thakur, Dow Hurst, JodiAnne T. Wood, Roger S. Gifford, Girija Rajarshi, Yingpeng Liu, Jimit Girish Raghav, Jason Jianxin Guo, Torbjörn U.C. Järbe, Patricia H. Reggio, Jack Bergman, and Alexandros Makriyannis . Probing the Carboxyester Side Chain in Controlled Deactivation (−)-Δ8-Tetrahydrocannabinols. Journal of Medicinal Chemistry 2015, 58 (2) , 665-681.
    11. Alexandros Makriyannis . 2012 Division of Medicinal Chemistry Award Address. Trekking the Cannabinoid Road: A Personal Perspective. Journal of Medicinal Chemistry 2014, 57 (10) , 3891-3911.
    12. Rishi Sharma, Spyros P. Nikas, Jason Jianxin Guo, Srikrishnan Mallipeddi, JodiAnne T. Wood, and Alexandros Makriyannis . C-Ring Cannabinoid Lactones: A Novel Cannabinergic Chemotype. ACS Medicinal Chemistry Letters 2014, 5 (4) , 400-404.
    13. Rishi Sharma, Spyros P. Nikas, Carol A. Paronis, JodiAnne T. Wood, Aneetha Halikhedkar, Jason Jianxin Guo, Ganesh A. Thakur, Shashank Kulkarni, Othman Benchama, Jimit Girish Raghav, Roger S. Gifford, Torbjörn U. C. Järbe, Jack Bergman, and Alexandros Makriyannis . Controlled-Deactivation Cannabinergic Ligands. Journal of Medicinal Chemistry 2013, 56 (24) , 10142-10157.
    14. Ganesh A. Thakur, Shama Bajaj, Carol Paronis, Yan Peng, Anna L. Bowman, Lawrence S. Barak, Marc G. Caron, Demon Parrish, Jeffrey R. Deschamps, and Alexandros Makriyannis . Novel Adamantyl Cannabinoids as CB1 Receptor Probes. Journal of Medicinal Chemistry 2013, 56 (10) , 3904-3921.
    15. Viktor Rempel, Nicole Volz, Sonja Hinz, Tadeusz Karcz, Irene Meliciani, Martin Nieger, Wolfgang Wenzel, Stefan Bräse, and Christa E. Müller . 7-Alkyl-3-benzylcoumarins: A Versatile Scaffold for the Development of Potent and Selective Cannabinoid Receptor Agonists and Antagonists. Journal of Medicinal Chemistry 2012, 55 (18) , 7967-7977.
    16. Lucio Minuti, Andrea Temperini, and Eleonora Ballerini . High-Pressure-Promoted Diels–Alder Approach to Biaryls: Application to the Synthesis of the Cannabinols Family. The Journal of Organic Chemistry 2012, 77 (18) , 7923-7931.
    17. Penchal Reddy Nandaluru and Graham J. Bodwell . Multicomponent Synthesis of 6H-Dibenzo[b,d]pyran-6-ones and a Total Synthesis of Cannabinol. Organic Letters 2012, 14 (1) , 310-313.
    18. Richard I. Duclos, Jr., Meghan Johnston, Subramanian K. Vadivel, Alexandros Makriyannis, Sherrye T. Glaser, and S. John Gatley . A Methodology for Radiolabeling of the Endocannabinoid 2-Arachidonoylglycerol (2-AG). The Journal of Organic Chemistry 2011, 76 (7) , 2049-2055.
    19. Spyros P. Nikas, Shakiru O. Alapafuja, Ioannis Papanastasiou, Carol A. Paronis, Vidyanand G. Shukla, Demetris P. Papahatjis, Anna L. Bowman, Aneetha Halikhedkar, Xiuwen Han, and Alexandros Makriyannis . Novel 1′,1′-Chain Substituted Hexahydrocannabinols: 9β-Hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a Highly Potent Cannabinoid Receptor 1 (CB1) Agonist. Journal of Medicinal Chemistry 2010, 53 (19) , 6996-7010.
    20. Kodumuru Vishnumurthy and Alexandros Makriyannis. Novel and Efficient One-Step Parallel Synthesis of Dibenzopyranones via Suzuki−Miyaura Cross Coupling. Journal of Combinatorial Chemistry 2010, 12 (5) , 664-669.
    21. Michał Achmatowicz, Oliver R. Thiel, Philip Wheeler, Charles Bernard, Jinkun Huang, Robert D. Larsen and Margaret M. Faul. Practical Synthesis of a p38 MAP Kinase Inhibitor. The Journal of Organic Chemistry 2009, 74 (2) , 795-809.
    22. Dai Lu, Jianxin Guo, Richard I. Duclos, Jr., Anna L. Bowman and Alexandros Makriyannis. Bornyl- and Isobornyl-Δ8-tetrahydrocannabinols: A Novel Class of Cannabinergic Ligands. Journal of Medicinal Chemistry 2008, 51 (20) , 6393-6399.
    23. Jesse A. Teske and Alexander Deiters. A Cyclotrimerization Route to Cannabinoids. Organic Letters 2008, 10 (11) , 2195-2198.
    24. Partha Pratim Dutta, Faruk Alam, Biplab Kumar Dey, Rajeev K. Tonk. Miscellany of Chromene. 2023, 245-280.
    25. Emma R. Carruthers, Natasha L. Grimsey. Cannabinoid CB 2 receptor orthologues; in vitro function and perspectives for preclinical to clinical translation. British Journal of Pharmacology 2023, 292
    26. H. Surya Prakash Rao, M. Prabakaran, Nandurka Muthanna. New method for synthesis of 7-hydroxydibenzopyran-6-ones: Benzannulation of coumarins by three-component condensation. Tetrahedron 2023, 132 , 133234.
    27. Eduardo Muñoz, Matthias Winkler, Marcus R Götz, Isabel González-Mariscal. Features of (+)-trans-cannabidiol-2-hydroxy pentyl and applications to disease: A focus on usage in diabetic nephropathy. 2023, 449-455.
    28. Ana Bagues, Yolanda López-Tofiño, Álvaro Llorente-Berzal, Raquel Abalo. Cannabinoid drugs against chemotherapy-induced adverse effects: focus on nausea/vomiting, peripheral neuropathy and chemofog in animal models. Behavioural Pharmacology 2022, 33 (2&3) , 105-129.
    29. Pradeep Paudel, Samir Ross, Xing-Cong Li. Molecular Targets of Cannabinoids Associated with Depression. Current Medicinal Chemistry 2022, 29 (11) , 1827-1850.
    30. Toru Amaya. 9‐Iodo‐9‐Borabicyclo[3.3.1]nonane. 2022, 1-4.
    31. Jenny L. Wilkerson, Lauren B. Alberti, Ganesh A. Thakur, Alexandros Makriyannis, Erin D. Milligan. Peripherally administered cannabinoid receptor 2 (CB2R) agonists lose anti-allodynic effects in TRPV1 knockout mice, while intrathecal administration leads to anti-allodynia and reduced GFAP, CCL2 and TRPV1 expression in the dorsal spinal cord and DRG. Brain Research 2022, 1774 , 147721.
    32. Paola Terrazas, Efrain Salamanca, Marcelo Dávila, Sophie Manner, Alberto Gimenez, Olov Sterner. SARs for the Antiparasitic Plant Metabolite Pulchrol. 3. Combinations of New Substituents in A/B-Rings and A/C-Rings. Molecules 2021, 26 (13) , 3944.
    33. Sant Kumar Verma, Niraj Kumar, Suresh Thareja. Gaussian field-based comparative 3D QSAR modelling for the identification of favourable pharmacophoric features of chromene derivatives as selective inhibitors of ALR2 over ALR1. Structural Chemistry 2021, 32 (3) , 1289-1298.
    34. Benjamin Brennecke, Thais Gazzi, Kenneth Atz, Jürgen Fingerle, Pascal Kuner, Torsten Schindler, Guy de Weck, Marc Nazaré, Uwe Grether. Cannabinoid Receptor Type 2 Ligands: An Analysis of Granted Patents Since 2010. Pharmaceutical Patent Analyst 2021, 10 (3) , 111-163.
    35. Thanh C. Ho, Marcus A. Tius, Spyros P. Nikas, Ngan K. Tran, Fei Tong, Han Zhou, Nikolai Zvonok, Alexandros Makriyannis. Oxa-adamantyl cannabinoids. Bioorganic & Medicinal Chemistry Letters 2021, 38 , 127882.
    36. Ana Bornadiego, Ana G. Neo, Carlos F. Marcos. Synthesis of Chromeno[3,4-b]piperazines by an Enol-Ugi/Reduction/Cyclization Sequence. Molecules 2021, 26 (5) , 1287.
    37. Jenny L. Wilkerson, Lauren B. Alberti, Audra A. Kerwin, Catherine A. Ledent, Ganesh A. Thakur, Alexandros Makriyannis, Erin D. Milligan. Peripheral versus central mechanisms of the cannabinoid type 2 receptor agonist AM1710 in a mouse model of neuropathic pain. Brain and Behavior 2020, 10 (12)
    38. Paola Terrazas, Efrain Salamanca, Marcelo Dávila, Sophie Manner, Alberto Giménez, Olov Sterner. SAR:s for the Antiparasitic Plant Metabolite Pulchrol. 1. The Benzyl Alcohol Functionality. Molecules 2020, 25 (13) , 3058.
    39. Primali V. Navaratne, Jenny L. Wilkerson, Kavindri D. Ranasinghe, Evgeniya Semenova, Jasmine S. Felix, Ion Ghiviriga, Adrian Roitberg, Lance R. McMahon, Alexander J. Grenning. Axially Chiral Cannabinols: A New Platform for Cannabinoid‐Inspired Drug Discovery. ChemMedChem 2020, 15 (9) , 728-732.
    40. Yingpeng Liu, Thanh C. Ho, Mohammed Baradwan, Maria Pascual Lopez-Alberca, Christos Iliopoulos-Tsoutsouvas, Spyros P. Nikas, Alexandros Makriyannis. Synthesis of Functionalized Cannabilactones. Molecules 2020, 25 (3) , 684.
    41. Shakiru O. Alapafuja, Spyros P. Nikas, Thanh C. Ho, Fei Tong, Othman Benchama, Alexandros Makriyannis. Chain Substituted Cannabilactones with Selectivity for the CB2 Cannabinoid Receptor. Molecules 2019, 24 (19) , 3559.
    42. Juan A. Páez, Nuria E. Campillo. Innovative Therapeutic Potential of Cannabinoid Receptors as Targets in Alzheimer’s Disease and Less Well-Known Diseases. Current Medicinal Chemistry 2019, 26 (18) , 3300-3340.
    43. Xiaodong Si, Yuanyuan Jia, Xinqi Luan, Luo Yang, Yong Pei, Wang Zhou. Insight into 6π Electrocyclic Reactions of 1,8‐Dioxatetraene. Angewandte Chemie 2019, 131 (9) , 2686-2690.
    44. Xiaodong Si, Yuanyuan Jia, Xinqi Luan, Luo Yang, Yong Pei, Wang Zhou. Insight into 6π Electrocyclic Reactions of 1,8‐Dioxatetraene. Angewandte Chemie International Edition 2019, 58 (9) , 2660-2664.
    45. Ai-Ling Li, Xiaoyan Lin, Amey S. Dhopeshwarkar, Ana Carla Thomaz, Lawrence M. Carey, Yingpeng Liu, Spyros P. Nikas, Alexandros Makriyannis, Ken Mackie, Andrea G. Hohmann. Cannabinoid CB2 Agonist AM1710 Differentially Suppresses Distinct Pathological Pain States and Attenuates Morphine Tolerance and Withdrawal. Molecular Pharmacology 2019, 95 (2) , 155-168.
    46. Thanh C. Ho, Marcus A. Tius. Synthesis of Classical/Nonclassical Hybrid Cannabinoids and Related Compounds. 2019, 247-289.
    47. Ana Bornadiego, Jesús Díaz, Carlos Fernández Marcos. Direct multicomponent synthesis of benzocoumarins. PeerJ Organic Chemistry 2019, 1 , e1.
    48. Michael S. Malamas, Jimit Girish Raghav, Xiaoyu Ma, Chandrashekhar Honrao, JodiAnne T. Wood, Othman Benchama, Han Zhou, Srikrishnan Mallipeddi, Alexandros Makriyannis. Oximes short-acting CB1 receptor agonists. Bioorganic & Medicinal Chemistry 2018, 26 (18) , 4963-4970.
    49. Federica Barutta, Graziella Bruno, Raffaella Mastrocola, Stefania Bellini, Gabriella Gruden. The role of cannabinoid signaling in acute and chronic kidney diseases. Kidney International 2018, 94 (2) , 252-258.
    50. . 2,2‐Dimethylbenzopyrans. 2018, 414-434.
    51. Richard C. Larock, Tanay Kesharwani. Formation of Ethers by Acetal, Carbonyl, and Ortho Ester Conversions. 2018, 1-90.
    52. Amey Dhopeshwarkar, Natalia Murataeva, Alex Makriyannis, Alex Straiker, Ken Mackie. Two Janus Cannabinoids That Are Both CB 2 Agonists and CB 1 Antagonists. Journal of Pharmacology and Experimental Therapeutics 2017, 360 (2) , 300-311.
    53. Marta Costa, Tatiana A. Dias, Alexandra Brito, Fernanda Proença. Biological importance of structurally diversified chromenes. European Journal of Medicinal Chemistry 2016, 123 , 487-507.
    54. Takayo Haruna, Masahiko Soga, Yasuhide Morioka, Ichiro Hikita, Kinichi Imura, Yoko Furue, Mina Yamamoto, Chihiro Imura, Minoru Ikeda, Akira Yamauchi, Masashi Deguchi, Michitaka Shichijo, Akinori Arimura, Kiyoshi Yasui. S-777469, a Novel Cannabinoid Type 2 Receptor Agonist, Suppresses Itch-Associated Scratching Behavior in Rodents through Inhibition of Itch Signal Transmission. Pharmacology 2015, 95 (1-2) , 95-103.
    55. Liting Deng, Josée Guindon, Benjamin L. Cornett, Alexandros Makriyannis, Ken Mackie, Andrea G. Hohmann. Chronic Cannabinoid Receptor 2 Activation Reverses Paclitaxel Neuropathy Without Tolerance or Cannabinoid Receptor 1–Dependent Withdrawal. Biological Psychiatry 2015, 77 (5) , 475-487.
    56. Elena Cichero, Giulia Menozzi, Sara Guariento, Paola Fossa. Ligand-based homology modelling of the human CB 2 receptor SR144528 antagonist binding site: a computational approach to explore the 1,5-diaryl pyrazole scaffold. MedChemComm 2015, 6 (11) , 1978-1986.
    57. H. Amhaoul, S. Staelens, S. Dedeurwaerdere. Imaging brain inflammation in epilepsy. Neuroscience 2014, 279 , 238-252.
    58. Fangfang Fan, Jingjing Dong, Jinqian Wang, Lina Song, Chuanjun Song, Junbiao Chang. An Intramolecular Pyranone Diels–Alder Cycloaddition Approach to Cannabinol. Advanced Synthesis & Catalysis 2014, 356 (6) , 1337-1342.
    59. Meghan Johnston, Shachi R. Bhatt, Surina Sikka, Richard W. Mercier, Jay M. West, Alexandros Makriyannis, S. John Gatley, Richard I. Duclos. Assay and inhibition of diacylglycerol lipase activity. Bioorganic & Medicinal Chemistry Letters 2012, 22 (14) , 4585-4592.
    60. Jenny L. Wilkerson, Katherine R. Gentry, Ellen C. Dengler, James A. Wallace, Audra A. Kerwin, Leisha M. Armijo, Megan N. Kuhn, Ganesh A. Thakur, Alexandros Makriyannis, Erin D. Milligan. Intrathecal cannabilactone CB2R agonist, AM1710, controls pathological pain and restores basal cytokine levels. Pain 2012, 153 (5) , 1091-1106.
    61. Jose Cumella, Laura Hernández‐Folgado, Rocio Girón, Eva Sánchez, Paula Morales, Dow P. Hurst, Maria Gómez‐Cañas, Maria Gómez‐Ruiz, Diana C. G. A. Pinto, Pilar Goya, Patricia H. Reggio, María Isabel Martin, Javier Fernández‐Ruiz, Artur M. S. Silva, Nadine Jagerovic. Chromenopyrazoles: Non‐psychoactive and Selective CB 1 Cannabinoid Agonists with Peripheral Antinociceptive Properties. ChemMedChem 2012, 7 (3) , 452-463.
    62. Jenny L. Wilkerson, Katherine R. Gentry, Ellen C. Dengler, James A. Wallace, Audra A. Kerwin, Megan N. Kuhn, Alexander M. Zvonok, Ganesh A. Thakur, Alexandros Makriyannis, Erin D. Milligan. Immunofluorescent spectral analysis reveals the intrathecal cannabinoid agonist, AM1241, produces spinal anti‐inflammatory cytokine responses in neuropathic rats exhibiting relief from allodynia. Brain and Behavior 2012, 2 (2) , 155-177.
    63. Brady K. Atwood, James Wager-Miller, Christopher Haskins, Alex Straiker, Ken Mackie. Functional Selectivity in CB 2 Cannabinoid Receptor Signaling and Regulation: Implications for the Therapeutic Potential of CB 2 Ligands. Molecular Pharmacology 2012, 81 (2) , 250-263.
    64. Liting Deng, Josée Guindon, V Kiran Vemuri, Ganesh A Thakur, Fletcher A White, Alexandros Makriyannis, Andrea G Hohmann. The Maintenance of Cisplatin- and Paclitaxel-Induced Mechanical and Cold Allodynia is Suppressed by Cannabinoid CB 2 Receptor Activation and Independent of CXCR4 Signaling in Models of Chemotherapy-Induced Peripheral Neuropathy. Molecular Pain 2012, 8 , 1744-8069-8-71.
    65. Jenny L. Wilkerson, Erin D. Milligan. The Central Role of Glia in Pathological Pain and the Potential of Targeting the Cannabinoid 2 Receptor for Pain Relief. ISRN Anesthesiology 2011, 2011 , 1-19.
    66. Heidi Teng, Ganesh A. Thakur, Alexandros Makriyannis. Conformationally constrained analogs of BAY 59–3074 as novel cannabinoid receptor ligands. Bioorganic & Medicinal Chemistry Letters 2011, 21 (19) , 5999-6002.
    67. Jiaying Luo, Youling Lu, Saiwen Liu, Jing Liu, Guo‐Jun Deng. Efficient One‐Pot Synthesis of Dibenzopyranones via a Decarboxylative Cross‐Coupling and Lactonization Sequence. Advanced Synthesis & Catalysis 2011, 353 (14-15) , 2604-2608.
    68. Elena Cichero, Alessia Ligresti, Marco Allarà, Vincenzo di Marzo, Zelda Lazzati, Pasqualina D’Ursi, Anna Marabotti, Luciano Milanesi, Andrea Spallarossa, Angelo Ranise, Paola Fossa. Homology modeling in tandem with 3D-QSAR analyses: A computational approach to depict the agonist binding site of the human CB2 receptor. European Journal of Medicinal Chemistry 2011, 46 (9) , 4489-4505.
    69. Nikita B. Ruparel, Amol M. Patwardhan, Armen N. Akopian, Kenneth M. Hargreaves. Desensitization of Transient Receptor Potential Ankyrin 1 (TRPA1) by the TRP Vanilloid 1-Selective Cannabinoid Arachidonoyl-2 Chloroethanolamine. Molecular Pharmacology 2011, 80 (1) , 117-123.
    70. Elizabeth J. Rahn, Ganesh A. Thakur, Jodi Anne T. Wood, Alexander M. Zvonok, Alexandros Makriyannis, Andrea G. Hohmann. Pharmacological characterization of AM1710, a putative cannabinoid CB2 agonist from the cannabilactone class: Antinociception without central nervous system side-effects. Pharmacology Biochemistry and Behavior 2011, 98 (4) , 493-502.
    71. Elena Cichero, Sara Cesarini, Luisa Mosti, Paola Fossa. CoMFA and CoMSIA analyses on 1,2,3,4-tetrahydropyrrolo[3,4-b]indole and benzimidazole derivatives as selective CB2 receptor agonists. Journal of Molecular Modeling 2010, 16 (9) , 1481-1498.
    72. Brady K Atwood, Ken Mackie. CB 2 : a cannabinoid receptor with an identity crisis. British Journal of Pharmacology 2010, 160 (3) , 467-479.
    73. Elena Cichero, Sara Cesarini, Luisa Mosti, Paola Fossa. CoMFA and CoMSIA analyses on 4-oxo-1,4-dihydroquinoline and 4-oxo-1,4-dihydro-1,5-, -1,6- and -1,8-naphthyridine derivatives as selective CB2 receptor agonists. Journal of Molecular Modeling 2010, 16 (4) , 677-691.
    74. Ganesh A Thakur, Ritesh Tichkule, Shama Bajaj, Alexandros Makriyannis. Latest advances in cannabinoid receptor agonists. Expert Opinion on Therapeutic Patents 2009, 19 (12) , 1647-1673.
    75. Michaela Kress, R. Kuner. Mode of action of cannabinoids on nociceptive nerve endings. Experimental Brain Research 2009, 196 (1) , 79-88.
    76. Andrea Behrenswerth, Nicole Volz, Jakob Toräng, Sonja Hinz, Stefan Bräse, Christa E. Müller. Synthesis and pharmacological evaluation of coumarin derivatives as cannabinoid receptor antagonists and inverse agonists. Bioorganic & Medicinal Chemistry 2009, 17 (7) , 2842-2851.
    77. Marco Mor, Alessio Lodola. Pharmacological Tools in Endocannabinoid Neurobiology. 2009, 87-110.
    78. David R. Janero, Subramanian K. Vadivel, Alexandros Makriyannis. Pharmacotherapeutic modulation of the endocannabinoid signalling system in psychiatric disorders: Drug-discovery strategies. International Review of Psychiatry 2009, 21 (2) , 122-133.
    79. Elizabeth J. Rahn, Alexander M. Zvonok, Ganesh A. Thakur, Atmaram D. Khanolkar, Alexandros Makriyannis, Andrea G. Hohmann. Selective Activation of Cannabinoid CB 2 Receptors Suppresses Neuropathic Nociception Induced by Treatment with the Chemotherapeutic Agent Paclitaxel in Rats. Journal of Pharmacology and Experimental Therapeutics 2008, 327 (2) , 584-591.
    80. Wayne E Childers, Adam M Gilbert, Jeffrey D Kennedy, Garth T Whiteside. Advances in the development of novel analgesics. Expert Opinion on Therapeutic Patents 2008, 18 (9) , 1027-1067.
    81. Daniel Pagé, Elise Balaux, Luc Boisvert, Ziping Liu, Claire Milburn, Maxime Tremblay, Zhongyong Wei, Simon Woo, Xuehong Luo, Yun-Xing Cheng, Hua Yang, Sanjay Srivastava, Fei Zhou, William Brown, Miroslaw Tomaszewski, Christopher Walpole, Leila Hodzic, Stéphane St-Onge, Claude Godbout, Dominic Salois, Keymal Payza. Novel benzimidazole derivatives as selective CB2 agonists. Bioorganic & Medicinal Chemistry Letters 2008, 18 (13) , 3695-3700.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Your Mendeley pairing has expired. Please reconnect