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

Derivatives of the Triazoloquinazoline Adenosine Antagonist (CGS15943) Are Selective for the Human A3 Receptor Subtype

View Author Information
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810
Cite this: J. Med. Chem. 1996, 39, 21, 4142–4148
Publication Date (Web):October 11, 1996
Copyright © 1996 American Chemical Society

    Article Views





    Other access options


    The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS15943) binds to human A3 receptors with high affinity (Ki = 14 nM), while it lacks affinity at rat A3 receptors. Acylated derivatives of the 5-amino group and other modifications were prepared in an effort to provide A3 subtype selectivity. Affinity was determined in radioligand binding assays at rat brain A1 and A2A receptors using [3H]-(R)-PIA ([3H]-(R)-N6-(phenylisopropyl)adenosine) and [3H]CGS 21680 ([3H]-2-[[4-(2-carboxy ethyl)phenyl]ethylamino]-5‘-(N-ethylcarbamoyl)adenosine), respectively. Affinity was determined at cloned human A3 receptors using [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)-5‘-(N-methylcarbamoyl)adenosine). A series of straight chain alkyl amides demonstrated that the optimal chain length occurs with the 5-N-propionyl derivative, 3, which had a Ki value of 7.7 nM at human A3 receptors, and was 40- and 14-fold selective vs rat A1 and A2A receptors, respectively. The 5-N-benzoyl derivative, 10, displayed Ki values of 680 and 273 nM at rat A1 and A2A receptors, respectively, and 3.0 nM at human A3 receptors. A 5-N-phenylacetyl derivative, 12, was 470-fold selective for human A3 vs rat A1 receptors with a Ki value of 0.65 nM. A conjugate of Boc-γ-aminobutyric acid was also prepared but was nonselective. Conversion of the 5-amino group of CGS15943 to an oxo function resulted in lower affinity but 15-fold selectivity for human A3 receptors.

    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.


     Correspondence to:  Dr. K. A. Jacobson, Bldg. 8A, Rm. B1A-19, NIH, NIDDK, LBC, Bethesda, MD 20892-0810. Tel:  (301) 496-9024. Fax:  (301) 480-8422. E-mail:  [email protected].

     Abstract published in Advance ACS Abstracts, October 1, 1996.

    Cited By

    This article is cited by 104 publications.

    1. Eline Pottie, R. Rama Suresh, Kenneth A. Jacobson, Christophe P. Stove. Assay-Dependent Inverse Agonism at the A3 Adenosine Receptor: When Neutral Is Not Neutral. ACS Pharmacology & Translational Science 2023, 6 (9) , 1266-1274.
    2. Fabian Wesseler, Stefan Lohmann, Daniel Riege, Jonas Halver, Aileen Roth, Christian Pichlo, Sabrina Weber, Masanari Takamiya, Eva Müller, Jana Ketzel, Jana Flegel, Adrian Gihring, Sepand Rastegar, Jessica Bertrand, Ulrich Baumann, Uwe Knippschild, Christian Peifer, Sonja Sievers, Herbert Waldmann, Dennis Schade. Phenotypic Discovery of Triazolo[1,5-c]quinazolines as a First-In-Class Bone Morphogenetic Protein Amplifier Chemotype. Journal of Medicinal Chemistry 2022, 65 (22) , 15263-15281.
    3. Sabrina Taliani, Concettina La Motta, Laura Mugnaini, Francesca Simorini, Silvia Salerno, Anna Maria Marini, Federico Da Settimo, Sandro Cosconati, Barbara Cosimelli, Giovanni Greco, Vittorio Limongelli, Luciana Marinelli, Ettore Novellino, Osele Ciampi, Simona Daniele, Maria Letizia Trincavelli and Claudia Martini . Novel N2-Substituted Pyrazolo[3,4-d]pyrimidine Adenosine A3 Receptor Antagonists: Inhibition of A3-Mediated Human Glioblastoma Cell Proliferation. Journal of Medicinal Chemistry 2010, 53 (10) , 3954-3963.
    4. Siew Lee Cheong, Anna Dolzhenko, Sonja Kachler, Silvia Paoletta, Stephanie Federico, Barbara Cacciari, Anton Dolzhenko, Karl-Norbert Klotz, Stefano Moro, Giampiero Spalluto and Giorgia Pastorin . The Significance of 2-Furyl Ring Substitution with a 2-(para-substituted) Aryl Group in a New Series of Pyrazolo-triazolo-pyrimidines as Potent and Highly Selective hA3 Adenosine Receptors Antagonists: New Insights into Structure−Affinity Relationship and Receptor−Antagonist Recognition. Journal of Medicinal Chemistry 2010, 53 (8) , 3361-3375.
    5. Barbara Cosimelli, Giovanni Greco, Marina Ehlardo, Ettore Novellino, Federico Da Settimo, Sabrina Taliani, Concettina La Motta, Marusca Bellandi, Tiziano Tuccinardi, Adriano Martinelli, Osele Ciampi, Maria Letizia Trincavelli and Claudia Martini. Derivatives of 4-Amino-6-hydroxy-2-mercaptopyrimidine as Novel, Potent, and Selective A3 Adenosine Receptor Antagonists. Journal of Medicinal Chemistry 2008, 51 (6) , 1764-1770.
    6. Pier Giovanni Baraldi,, Mojgan Aghazadeh Tabrizi,, Stefania Gessi, and, Pier Andrea Borea. Adenosine Receptor Antagonists:  Translating Medicinal Chemistry and Pharmacology into Clinical Utility. Chemical Reviews 2008, 108 (1) , 238-263.
    7. Zhan-Guo Gao, John A. Auchampach, Kenneth A. Jacobson. Species dependence of A3 adenosine receptor pharmacology and function. Purinergic Signalling 2023, 19 (3) , 523-550.
    8. Filippo Prencipe, Tatiana Da Ros, Eleonora Cescon, Ilenia Grieco, Margherita Persico, Giampiero Spalluto, Stephanie Federico. Adenosine Receptor Ligands, Probes, and Functional Conjugates: A 20-Year History of Pyrazolo[4,3-e][1,2,4]Triazolo[1,5-c]Pyrimidines (PTP). 2023, 47-87.
    9. Tejinder Kaur, Brenna Weadick, Thomas A. Mace, Kajal Desai, Hannah Odom, Rajgopal Govindarajan. Nucleoside transporters and immunosuppressive adenosine signaling in the tumor microenvironment: Potential therapeutic opportunities. Pharmacology & Therapeutics 2022, 240 , 108300.
    10. Jorge Barbazán, Maria Majellaro, Antón L. Martínez, José M. Brea, Eddy Sotelo, Miguel Abal. Identification of A2BAR as a potential target in colorectal cancer using novel fluorescent GPCR ligands. Biomedicine & Pharmacotherapy 2022, 153 , 113408.
    11. Manish Rawat, Toshiaki Taniike, Diwan S. Rawat. Magnetically Separable Fe 3 O 4 @poly( m‐ phenylenediamine)@Cu 2 O Nanocatalyst for the Facile Synthesis of 5‐phenyl‐[1,2,3]triazolo[1,5‐c]quinazolines. ChemCatChem 2022, 14 (5)
    12. Zhan-Guo Gao, R. Rama Suresh, Kenneth A. Jacobson. Pharmacological characterization of DPTN and other selective A3 adenosine receptor antagonists. Purinergic Signalling 2021, 17 (4) , 737-746.
    13. Hatem A. Abuelizz, Rashad Al-Salahi. An overview of triazoloquinazolines: Pharmacological significance and recent developments. Bioorganic Chemistry 2021, 115 , 105263.
    14. Yulya Martynenko, Oleksii Antypenko, Inna Nosulenko, Galina Berest, Sergii Kovalenko. Directed Search of Anti-inflammatory Agents Among (3HQuinazoline- 4-ylidene)hydrazides of N-protected Amino acids and their Heterocyclization Products. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 2020, 19 (1) , 61-73.
    15. Raghu P. Mailavaram, Omar H.A. Al-Attraqchi, Supratik Kar, Shinjita Ghosh. Current Status in the Design and Development of Agonists and Antagonists of Adenosine A3 Receptor as Potential Therapeutic Agents. Current Pharmaceutical Design 2019, 25 (25) , 2772-2787.
    16. Enrico Margiotta, Stefano Moro. A Comparison in the Use of the Crystallographic Structure of the Human A1 or the A2A Adenosine Receptors as a Template for the Construction of a Homology Model of the A3 Subtype. Applied Sciences 2019, 9 (5) , 821.
    17. Kenneth A. Jacobson, Stefania Merighi, Katia Varani, Pier Andrea Borea, Stefania Baraldi, Mojgan Aghazadeh Tabrizi, Romeo Romagnoli, Pier Giovanni Baraldi, Antonella Ciancetta, Dilip K. Tosh, Zhan‐Guo Gao, Stefania Gessi. A 3 Adenosine Receptors as Modulators of Inflammation: From Medicinal Chemistry to Therapy. Medicinal Research Reviews 2018, 38 (4) , 1031-1072.
    18. Kenneth A. Jacobson, Dilip K. Tosh, Zhan-Guo Gao, Jinha Yu, Rama R. Suresh, Harsha Rao, Romeo Romagnoli, Pier Giovanni Baraldi, Mojgan Aghazadeh Tabrizi. Medicinal Chemistry of the A3 Adenosine Receptor. 2018, 169-198.
    19. Daniela Poli, Matteo Falsini, Flavia Varano, Marco Betti, Katia Varani, Fabrizio Vincenzi, Anna Maria Pugliese, Felicita Pedata, Diego Dal Ben, Ajiroghene Thomas, Ilaria Palchetti, Francesca Bettazzi, Daniela Catarzi, Vittoria Colotta. Imidazo[1,2-a]pyrazin-8-amine core for the design of new adenosine receptor antagonists: Structural exploration to target the A3 and A2A subtypes. European Journal of Medicinal Chemistry 2017, 125 , 611-628.
    20. Flavia Varano, Daniela Catarzi, Lucia Squarcialupi, Marco Betti, Fabrizio Vincenzi, Annalisa Ravani, Katia Varani, Diego Dal Ben, Ajiroghene Thomas, Rosaria Volpini, Vittoria Colotta. Exploring the 7-oxo-thiazolo[5,4-d]pyrimidine core for the design of new human adenosine A3 receptor antagonists. Synthesis, molecular modeling studies and pharmacological evaluation. European Journal of Medicinal Chemistry 2015, 96 , 105-121.
    21. Daniela Catarzi, Flavia Varano, Daniela Poli, Lucia Squarcialupi, Marco Betti, Letizia Trincavelli, Claudia Martini, Diego Dal Ben, Ajiroghene Thomas, Rosaria Volpini, Vittoria Colotta. 1,2,4-Triazolo[1,5-a]quinoxaline derivatives and their simplified analogues as adenosine A3 receptor antagonists. Synthesis, structure–affinity relationships and molecular modeling studies. Bioorganic & Medicinal Chemistry 2015, 23 (1) , 9-21.
    22. Pier Andrea Borea, Katia Varani, Fabrizio Vincenzi, Pier Giovanni Baraldi, Mojgan Aghazadeh Tabrizi, Stefania Merighi, Stefania Gessi, . The A 3 Adenosine Receptor: History and Perspectives. Pharmacological Reviews 2015, 67 (1) , 74-102.
    23. Elena Casale, Nadia Amboldi, Maria Gabriella Brasca, Dannica Caronni, Nicoletta Colombo, Claudio Dalvit, Eduard R. Felder, Gianpaolo Fogliatto, Arturo Galvani, Antonella Isacchi, Paolo Polucci, Laura Riceputi, Francesco Sola, Carlo Visco, Fabio Zuccotto, Francesco Casuscelli. Fragment-based hit discovery and structure-based optimization of aminotriazoloquinazolines as novel Hsp90 inhibitors. Bioorganic & Medicinal Chemistry 2014, 22 (15) , 4135-4150.
    24. Stephen P.H. Alexander, Helen E. Benson, Elena Faccenda, Adam J. Pawson, Joanna L. Sharman, Michael Spedding, John A. Peters, Anthony J. Harmar, . The Concise Guide to PHARMACOLOGY 2013/14: G Protein-Coupled Receptors. British Journal of Pharmacology 2013, 170 (8) , 1459-1581.
    25. Michael F. Jarvis. Characterization of P1 (Adenosine) Purinoceptors. Current Protocols in Pharmacology 2013, 62 (1)
    26. Priyankar Paira, Mun Juinn Chow, Gopalakrishnan Venkatesan, Vamsi Krishna Kosaraju, Siew Lee Cheong, Karl‐Norbert Klotz, Wee Han Ang, Giorgia Pastorin. Organoruthenium Antagonists of Human A 3 Adenosine Receptors. Chemistry – A European Journal 2013, 19 (25) , 8321-8330.
    27. Anna Maria Almerico, Marco Tutone, Licia Pantano, Antonino Lauria. A3 adenosine receptor: Homology modeling and 3D-QSAR studies. Journal of Molecular Graphics and Modelling 2013, 42 , 60-72.
    28. Siew Lee Cheong, Stephanie Federico, Gopalakrishnan Venkatesan, Alexander Laurence Mandel, Yi‐Ming Shao, Stefano Moro, Giampiero Spalluto, Giorgia Pastorin. The A 3 adenosine receptor as multifaceted therapeutic target: pharmacology, medicinal chemistry, and in silico approaches. Medicinal Research Reviews 2013, 33 (2) , 235-335.
    29. Francesco Sirci, Laura Goracci, David Rodríguez, Jacqueline van Muijlwijk-Koezen, Hugo Gutiérrez-de-Terán, Raimund Mannhold. Ligand-, structure- and pharmacophore-based molecular fingerprints: a case study on adenosine A1, A2A, A2B, and A3 receptor antagonists. Journal of Computer-Aided Molecular Design 2012, 26 (11) , 1247-1266.
    30. ZheJun Xu, FeiXiong Cheng, Jie Li, YaDi Zhou, Ni Su, WeiHua Li, GuiXia Liu, Yun Tang. Comparative pharmacophore modeling of human adenosine receptor A1 and A3 antagonists. Science China Chemistry 2012, 55 (11) , 2407-2418.
    31. Eszter Kozma, T. Santhosh Kumar, Stephanie Federico, Khai Phan, Ramachandran Balasubramanian, Zhan-Guo Gao, Silvia Paoletta, Stefano Moro, Giampiero Spalluto, Kenneth A. Jacobson. Novel fluorescent antagonist as a molecular probe in A3 adenosine receptor binding assays using flow cytometry. Biochemical Pharmacology 2012, 83 (11) , 1552-1561.
    32. Judit Hodrea, Gyöngyike Majai, Zoltán Doró, Gábor Zahuczky, Attila Pap, Éva Rajnavölgyi, László Fésüs. The glucocorticoid dexamethasone programs human dendritic cells for enhanced phagocytosis of apoptotic neutrophils and inflammatory response. Journal of Leukocyte Biology 2011, 91 (1) , 127-136.
    33. Siew Lee Cheong, Stephanie Federico, Gopalakrishnan Venkatesan, Priyankar Paira, Yi-Ming Shao, Giampiero Spalluto, Chun Wei Yap, Giorgia Pastorin. Pharmacophore elucidation for a new series of 2-aryl-pyrazolo-triazolo-pyrimidines as potent human A3 adenosine receptor antagonists. Bioorganic & Medicinal Chemistry Letters 2011, 21 (10) , 2898-2905.
    34. Pier Giovanni Baraldi, Romeo Romagnoli, Giulia Saponaro, Stefania Baraldi, Mojgan Aghazadeh Tabrizi, Delia Preti. A3 Adenosine Receptor Antagonists: History and Future Perspectives. 2010, 121-147.
    35. Raul Chavez-Valdez, Marsha Wills-Karp, Rajni Ahlawat, Elizabeth A Cristofalo, Amy Nathan, Estelle B Gauda. Caffeine Modulates TNF-α Production by Cord Blood Monocytes: The Role of Adenosine Receptors. Pediatric Research 2009, 65 (2) , 203-208.
    36. Gloria Cristalli, Christa E. Müller, Rosaria Volpini. Recent Developments in Adenosine A2A Receptor Ligands. 2009, 59-98.
    37. Kenneth A. Jacobson, Athena M. Klutz, Dilip K. Tosh, Andrei A. Ivanov, Delia Preti, Pier Giovanni Baraldi. Medicinal Chemistry of the A3 Adenosine Receptor: Agonists, Antagonists, and Receptor Engineering. 2009, 123-159.
    38. Lijun Zhang, Daxin Shi, Jiarong Li, Ling Zhang, Yanqiu Fan. 1-Phenyl-6,7,8,9-hexahydro-1 H ,5 H -cyclohepta[1′,2′:2,3]pyrido[6,5- c ]pyrazol-4-amine: a new tacrine analogue. Acta Crystallographica Section E Structure Reports Online 2008, 64 (6) , o1056-o1056.
    39. Vittoria Colotta, Daniela Catarzi, Flavia Varano, Ombretta Lenzi, Guido Filacchioni, Claudia Martini, Letizia Trincavelli, Osele Ciampi, Chiara Traini, Anna Maria Pugliese, Felicita Pedata, Erika Morizzo, Stefano Moro. Synthesis, ligand–receptor modeling studies and pharmacological evaluation of novel 4-modified-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives as potent and selective human A3 adenosine receptor antagonists. Bioorganic & Medicinal Chemistry 2008, 16 (11) , 6086-6102.
    40. Maykel Pérez González, Carmen Terán, Marta Teijeira. Search for new antagonist ligands for adenosine receptors from QSAR point of view. How close are we?. Medicinal Research Reviews 2008, 28 (3) , 329-371.
    41. Lak Shin Jeong, Hyuk Woo Lee, Hea Ok Kim, Dilip K. Tosh, Shantanu Pal, Won Jun Choi, Zhan-Guo Gao, Amit R. Patel, Wanda Williams, Kenneth A. Jacobson, Hee-Doo Kim. Structure–activity relationships of 2-chloro-N6-substituted-4′-thioadenosine-5′-N,N-dialkyluronamides as human A3 adenosine receptor antagonists. Bioorganic & Medicinal Chemistry Letters 2008, 18 (5) , 1612-1616.
    42. G. Hajós, Z. Riedl. Bicyclic 5-6 Systems with One Bridgehead (Ring Junction) Nitrogen Atom: Three Extra Heteroatoms 2:1. 2008, 671-763.
    43. Seiji Miwatashi, Yasuyoshi Arikawa, Tatsumi Matsumoto, Keiko Uga, Naoyuki Kanzaki, Yumi N. Imai, Shigenori Ohkawa. Synthesis and Biological Activities of 4-Phenyl-5-pyridyl-1,3-thiazole Derivatives as Selective Adenosine A3 Antagonists. Chemical and Pharmaceutical Bulletin 2008, 56 (8) , 1126-1137.
    44. Sara Bar-Yehuda, Michael H Silverman, William D Kerns, Avivit Ochaion, Shira Cohen, Pnina Fishman. The anti-inflammatory effect of A 3 adenosine receptor agonists: a novel targeted therapy for rheumatoid arthritis. Expert Opinion on Investigational Drugs 2007, 16 (10) , 1601-1613.
    45. Barbara Cacciari, Chiara Bolcato, Giampiero Spalluto, Karl-Norbet Klotz, Magdalena Bacilieri, Francesca Deflorian, Stefano Moro. Pyrazolo-triazolo-pyrimidines as adenosine receptor antagonists: A complete structure–activity profile. Purinergic Signalling 2007, 3 (3) , 183-193.
    46. Jia Rong Li, Li Jun Zhang, Jin Nan Chen, Xi Quan Yang, Li Jun Wang, Xiao Fan Zhao, Jun Xia Qiu. Synthesis of 2H-3,1-pyrazolo[3,4-e]oxazines via a new conversion of Friedländer reaction. Chinese Chemical Letters 2007, 18 (6) , 636-638.
    47. Gloria Cristalli, Barbara Cacciari, Diego Dal Ben, Catia Lambertucci, Stefano Moro, Giampiero Spalluto, Rosaria Volpini. Highlights on the Development of A 2A Adenosine Receptor Agonists and Antagonists. ChemMedChem 2007, 2 (3) , 260-281.
    48. Karl-Norbert Klotz, Nico Falgner, Sonja Kachler, Catia Lambertucci, Sauro Vittori, Rosaria Volpini, Gloria Cristalli. [3H]HEMADO— a novel tritiated agonist selective for the human adenosine A3 receptor. European Journal of Pharmacology 2007, 556 (1-3) , 14-18.
    49. Michael Williams. MRS 1220. 2007, 1-2.
    50. Marina Hermes, Hartmut Osswald, Doris Kloor. Role of S-adenosylhomocysteine hydrolase in adenosine-induced apoptosis in HepG2 cells. Experimental Cell Research 2007, 313 (2) , 264-283.
    51. Dooil Kim, Suk-In Hong, Dae-Sil Lee. Triazoloquinazolines as Human A3 Adenosine Receptor Antagonists: A QSAR Study. International Journal of Molecular Sciences 2006, 7 (11) , 485-496.
    52. Margot W. Beukers, Illiana Meurs, Adriaan P. IJzerman. Structure-affinity relationships of adenosine A2B receptor ligands. Medicinal Research Reviews 2006, 26 (5) , 667-698.
    53. Michael P. DeNinno, Hiroko Masamune, Lois K. Chenard, Kenneth J. DiRico, Cynthia Eller, John B. Etienne, Jeanene E. Tickner, Scott P. Kennedy, Delvin R. Knight, Jimmy Kong, Joseph J. Oleynek, W. Ross Tracey, Roger J. Hill. The synthesis of highly potent, selective, and water-soluble agonists at the human adenosine A3 receptor. Bioorganic & Medicinal Chemistry Letters 2006, 16 (9) , 2525-2527.
    54. Raquel Guinzberg, Daniel Cortés, Antonio Díaz-Cruz, Héctor Riveros-Rosas, Rafael Villalobos-Molina, Enrique Piña. Inosine released after hypoxia activates hepatic glucose liberation through A 3 adenosine receptors. American Journal of Physiology-Endocrinology and Metabolism 2006, 290 (5) , E940-E951.
    55. L. Yates, J. H. Clark, T. J. Martin, S. James, K. J. Broadley, E. J. Kidd. Radioligand binding and functional responses of ligands for human recombinant adenosine A 3 receptors. Autonomic and Autacoid Pharmacology 2006, 26 (2) , 191-200.
    56. Stefano Moro, Zhan‐Guo Gao, Kenneth A. Jacobson, Giampiero Spalluto. Progress in the pursuit of therapeutic adenosine receptor antagonists. Medicinal Research Reviews 2006, 26 (2) , 131-159.
    57. Anna Maria Pugliese, Elisabetta Coppi, Giampiero Spalluto, Renato Corradetti, Felicita Pedata. A 3 adenosine receptor antagonists delay irreversible synaptic failure caused by oxygen and glucose deprivation in the rat CA1 hippocampus in vitro. British Journal of Pharmacology 2006, 147 (5) , 524-532.
    58. Zhan-Guo Gao, Bhalchandra V. Joshi, Athena M. Klutz, Soo-Kyung Kim, Hyuk Woo Lee, Hea Ok Kim, Lak Shin Jeong, Kenneth A. Jacobson. Conversion of A3 adenosine receptor agonists into selective antagonists by modification of the 5′-ribofuran-uronamide moiety. Bioorganic & Medicinal Chemistry Letters 2006, 16 (3) , 596-601.
    59. M. Verónica Donoso, Rodrigo López, Ramiro Miranda, René Briones, J. Pablo Huidobro-Toro. A 2B adenosine receptor mediates human chorionic vasoconstriction and signals through arachidonic acid cascade. American Journal of Physiology-Heart and Circulatory Physiology 2005, 288 (5) , H2439-H2449.
    60. Giorgia Pastorin, Chiara Bolcato, Barbara Cacciari, Sonja Kachler, Karl-Norbert Klotz, Christian Montopoli, Stefano Moro, Giampiero Spalluto. Synthesis, biological studies and molecular modeling investigation of 1,3-dimethyl-2,4-dioxo-6-methyl-8-(substituted) 1,2,3,4-tetrahydro [1,2,4]-triazolo [3,4-f]-purines as potential adenosine receptor antagonists. Il Farmaco 2005, 60 (4) , 299-306.
    61. Daniela Catarzi, Vittoria Colotta, Flavia Varano, Francesca Romana Calabri, Ombretta Lenzi, Guido Filacchioni, Letizia Trincavelli, Claudia Martini, Andrea Tralli, Christian Montopoli, Stefano Moro. 2-Aryl-8-chloro-1,2,4-triazolo[1,5-a]quinoxalin-4-amines as highly potent A1 and A3 adenosine receptor antagonists. Bioorganic & Medicinal Chemistry 2005, 13 (3) , 705-715.
    62. Takashi Okamura, Yasuhisa Kurogi, Kinji Hashimoto, Hiroshi Nishikawa, Yoshimitsu Nagao. Facile synthesis of fused 1,2,4-triazolo[1,5-c]pyrimidine derivatives as human adenosine A3 receptor ligands. Bioorganic & Medicinal Chemistry Letters 2004, 14 (10) , 2443-2446.
    63. Andrea Thiele, Romy Kronstein, Anne Wetzel, Anja Gerth, Karen Nieber, Sunna Hauschildt. Regulation of Adenosine Receptor Subtypes during Cultivation of Human Monocytes: Role of Receptors in Preventing Lipopolysaccharide-Triggered Respiratory Burst. Infection and Immunity 2004, 72 (3) , 1349-1357.
    64. Kwan-Young Jung, Soo-Kyung Kim, Zhan-Guo Gao, Ariel S Gross, Neli Melman, Kenneth A Jacobson, Yong-Chul Kim. Structure–activity relationships of thiazole and thiadiazole derivatives as potent and selective human adenosine A3 receptor antagonists. Bioorganic & Medicinal Chemistry 2004, 12 (3) , 613-623.
    65. Pier Giovanni Baraldi, Mojgan Aghazadeh Tabrizi, Andrea Bovero, Barbara Avitabile, Delia Preti, Francesca Fruttarolo, Romeo Romagnoli, Katia Varani, Pier Andrea Borea. Recent developments in the field of A2A and A3 adenosine receptor antagonists. European Journal of Medicinal Chemistry 2003, 38 (4) , 367-382.
    66. Pier Giovanni Baraldi, Mojgan Aghazadeh Tabrizi, Francesca Fruttarolo, Andrea Bovero, Barbara Avitabile, Delia Preti, Romeo Romagnoli, Stefania Merighi, Stefania Gessi, Katia Varani, Pier Andrea Borea. Recent developments in the field of A 3 adenosine receptor antagonists. Drug Development Research 2003, 58 (4) , 315-329.
    67. Chi-Chung Chou, Thomas W. Vickroy. Antagonism of adenosine receptors by caffeine and caffeine metabolites in equine forebrain tissues. American Journal of Veterinary Research 2003, 64 (2) , 216-224.
    68. Kenneth A. Jacobson, Susanna Tchilibon, Bhalchandra V. Joshi, Zhan-Guo Gao. Chapter 13. A3 adenosine receptors. 2003, 121-130.
    69. M. L. Trincavelli, D. Tuscano, M. Marroni, A. Falleni, V. Gremigni, S. Ceruti, M. P. Abbracchio, K. A. Jacobson, F. Cattabeni, C. Martini. A 3 Adenosine Receptors in Human Astrocytoma Cells: Agonist-Mediated Desensitization, Internalization, and Down-Regulation. Molecular Pharmacology 2002, 62 (6) , 1373-1384.
    70. Lazaros C. Foukas, Nathalie Daniele, Chariklia Ktori, Karen E. Anderson, Jørgen Jensen, Peter R. Shepherd. Direct Effects of Caffeine and Theophylline on p110δ and Other Phosphoinositide 3-Kinases. Journal of Biological Chemistry 2002, 277 (40) , 37124-37130.
    71. M. A. Hassan Talukder, R. Ray Morrison, Marlene A. Jacobson, Kenneth A. Jacobson, Catherine Ledent, S. Jamal Mustafa. Targeted deletion of adenosine A 3 receptors augments adenosine-induced coronary flow in isolated mouse heart. American Journal of Physiology-Heart and Circulatory Physiology 2002, 282 (6) , H2183-H2189.
    72. Mayumi Saki, Hiroshi Tsumuki, Hiromi Nonaka, Junichi Shimada, Michio Ichimura. KF26777 (2-(4-bromophenyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one dihydrochloride), a new potent and selective adenosine A3 receptor antagonist. European Journal of Pharmacology 2002, 444 (3) , 133-141.
    73. Sonja Hess. Recent advances in adenosine receptor antagonist research. Expert Opinion on Therapeutic Patents 2001, 11 (10) , 1533-1561.
    74. Ye Chen, Michel P. Rathbone, Leif Hertz. Guanosine‐induced increase in free cytosolic calcium concentration in mouse astrocytes in primary cultures: Does it act on an A3 adenosine receptor?. Journal of Neuroscience Research 2001, 65 (2) , 184-189.
    75. Charles I. Ezeamuzie. Involvement of A 3 receptors in the potentiation by adenosine of the inhibitory effect of theophylline on human eosinophil degranulation: possible novel mechanism of the anti-inflammatory action of theophylline 1 1Abbreviations: C5a, complement fragment 5a; ECP, eosinophil cationic protein; EDN, eosinophil-derived neurotoxin; EPO, eosinophil peroxidase; OPD, O-phenylenediamine; CGS 21680, 2-[[2-[4-(2-carboxyethyl)phenyl]ethyl]amino]-N-ethylcarboxamidoadenosine; CPA, N-cyclopentyladenosine; DMPX, 3,7-dimethyl-1-propargylxanthine; DPCPX, 1,3-dipropyly-8-cyclo-pentylxanthine; IB-MECA, N6-(3-iodobenzyl)-5′-N-methylcarbamoyladen-osine; MBP, major basic protein; MRS1220, 9-chloro-2-(2-furyl)-5-phenyl-actylamino[1,2,4]triazolo[1,5-c]quinazoline; PDE, phosphodiesterase; cAMP, adenosine 3′,5′-cyclic monophosphate.. Biochemical Pharmacology 2001, 61 (12) , 1551-1559.
    76. MARIA P. ABBRACCHIO, ALESSANDRA CAMURRI, STEFANIA CERUTI, FLAMINIO CATTABENI, LOREDANA FALZANO, ANNA MARIA GIAMMARIOLI, KENNETH A. JACOBSON, LETIZIA TRINCAVELLI, CLAUDIA MARTINI, WALTER MALORNI, CARLA FIORENTINI. The A 3 Adenosine Receptor Induces Cytoskeleton Rearrangement in Human Astrocytoma Cells via a Specific Action on Rho Proteins. Annals of the New York Academy of Sciences 2001, 939 (1) , 63-73.
    77. K. A. Jacobson, L. J. S. Knutsen. P1 and P2 Purine and Pyrimidine Receptor Ligands. 2001, 129-175.
    78. A Brand, Z Vissiennon, D Eschke, K Nieber. Adenosine A1 and A3 receptors mediate inhibition of synaptic transmission in rat cortical neurons. Neuropharmacology 2001, 40 (1) , 85-95.
    79. Jacqueline E. Van Muijlwijk-Koezen, Henk Timmerman, Adriaan P. Ijzerman. 2 The Adenosine A3 Receptor and its Ligands. 2001, 61-113.
    80. Pier Giovanni Baraldi, Barbara Cacciari, Romeo Romagnoli, Giampiero Spalluto, Katia Varani, Stefania Gessi, Stefania Merighi, Pier Andrea Borea. Pyrazolo[4,3‐e]1,2,4‐triazolo[1,5‐c]pyrimidine derivatives: A new pharmacological tool for the characterization of the human A 3 adenosine receptor. Drug Development Research 2001, 52 (1-2) , 406-415.
    81. Suyou Liu, Xuhong Qian, Gonghua Song, Jing Chen, Weidong Chen. Fluorine containing heterocyclic compounds: synthesis of 6-substituted-2-substituted-aryl-1,2,4-triazolo[5,1-b] 1,3,5-thiadiazin-7-one derivatives. Journal of Fluorine Chemistry 2000, 105 (1) , 111-115.
    82. Mahmood S Mozaffari, Worku Abebe, Brett K Warren. Renal adenosine A 3 receptors in the rat: assessment of functional role. Canadian Journal of Physiology and Pharmacology 2000, 78 (5) , 428-432.
    83. Pier Giovanni Baraldi, Barbara Cacciari, Romeo Romagnoli, Stefania Merighi, Katia Varani, Pier Andrea Borea, Giampiero Spalluto. A3 Adenosine Receptor Ligands: History and Perspectives. Medicinal Research Reviews 2000, 20 (2) , 103-128.<103::AID-MED1>3.0.CO;2-X
    84. Thomas R Webb, Neli Melman, Dmitriy Lvovskiy, Xiao-duo Ji, Kenneth A Jacobson. The utilization of a unified pharmacophore query in the discovery of new antagonists of the adenosine receptor family. Bioorganic & Medicinal Chemistry Letters 2000, 10 (1) , 31-34.
    85. Rashmi A. Mittal, Chee‐Hong Tan, Hoon‐Eng Khoo. Adenosine modulates cell growth in baby hamster kidney (BHK) cells. BioFactors 2000, 11 (4) , 247-256.
    86. Maarten de Zwart, Roel C. Vollinga, Margot W. Beukers, Danielle F. Sleegers, Jacobien K. von Frijtag Drabbe K�nzel, Miriam de Groote, Ad P. Ijzerman. Potent antagonists for the human adenosine A2B receptor. Derivatives of the triazolotriazine adenosine receptor antagonist ZM241385 with high affinity. Drug Development Research 1999, 48 (3) , 95-103.<95::AID-DDR1>3.0.CO;2-B
    87. Charles I Ezeamuzie, Elizabeth Philips. Adenosine A 3 receptors on human eosinophils mediate inhibition of degranulation and superoxide anion release. British Journal of Pharmacology 1999, 127 (1) , 188-194.
    88. Kenneth A. Jacobson, Stefano Moro, Yong-Chul Kim, An-Hu Li. A3 adenosine receptors: Protective vs. damaging effects identified using novel agonists and antagonists. Drug Development Research 1998, 45 (3-4) , 113-124.<113::AID-DDR5>3.0.CO;2-S
    89. Erica W. van Tilburg, Jacqueline E. van Muijlwijk-Koezen, Adriaan P. Ijzerman. Medicinal chemistry of the human adenosine A3 receptor. Drug Development Research 1998, 45 (3-4) , 182-189.<182::AID-DDR15>3.0.CO;2-E
    90. Maria P. Abbracchio, Stefania Ceruti, Roberta Brambilla, Daniela Barbieri, Alessandra Camurri, Claudio Franceschi, Anna Maria Giammarioli, Kenneth A. Jacobson, Flaminio Cattabeni, Walter Malorni. Adenosine A3 receptors and viability of astrocytes. Drug Development Research 1998, 45 (3-4) , 379-386.<379::AID-DDR38>3.0.CO;2-Y
    91. Kyung-sun Park, Carsten Hoffmann, Hea Ok Kim, William L. Padgett, John W. Daly, Roberta Brambilla, Cristina Motta, Maria P. Abbracchio, Kenneth A. Jacobson. Activation and desensitization of rat A3-adenosine receptors by selective adenosine derivatives and xanthine-7-ribosides. Drug Development Research 1998, 44 (2-3) , 97-105.<97::AID-DDR7>3.0.CO;2-5
    92. K. Varani, B. Cacciari, P.G. Baraldi, S. Dionisotti, E. Ongini, P.A. Borea. Binding affinity of adenosine receptor agonists and antagonists at human cloned A3 adenosine receptors. Life Sciences 1998, 63 (5) , PL81-PL87.
    93. Sally-Ann Poulsen, Ronald J Quinn. Adenosine receptors: new opportunities for future drugs. Bioorganic & Medicinal Chemistry 1998, 6 (6) , 619-641.
    94. K.A. Jacobson. Adenosine A3 receptors: novel ligands and paradoxical effects. Trends in Pharmacological Sciences 1998, 19 (5) , 184-191.
    95. Michael F. Jarvis. Characterization of P1 (Adenosine) Purinoceptors. Current Protocols in Pharmacology 1998, 00 (1)
    96. Michael P. DeNinno. Adenosine. 1998, 111-120.
    97. Joel Linden, Kenneth A. Jacobson. Molecular Biology and Pharmacology of Recombinant Adenosine Receptors. 1998, 1-20.
    98. Ennio Ongini. SCH 58261: A selective A2A adenosine receptor antagonists. Drug Development Research 1997, 42 (2) , 63-70.<63::AID-DDR2>3.0.CO;2-N
    99. Kenneth A. Jacobson, Kyung-Sun Park, Ji-Long Jiang, Yong-Chul Kim, Mark E. Olah, Gary L. Stiles, Xiao-Duo Ji. Pharmacological characterization of novel A3 adenosine receptor-selective antagonists. Neuropharmacology 1997, 36 (9) , 1157-1165.
    100. John C Shryock, Luiz Belardinelli. Adenosine and Adenosine Receptors in the Cardiovascular System: Biochemistry, Physiology, and Pharmacology. The American Journal of Cardiology 1997, 79 (12) , 2-10.
    Load all citations

    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