Medicinal chemistry of adenosine, P2Y and P2X receptors

Neuropharmacology

Volumn 104, Issue , 2016, Pages 31-49

  Jacobson, Kenneth A ^a,c   Müller, Christa E ^b  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b UNIVERSITY OF BONN   (Germany)

^c Bldg 8A ^*  (United States)

Author keywords

Agonists; Antagonists; ATP; GPCR; Ion channel; Nucleosides; Nucleotides

Indexed keywords

1,4 DIHYDRO 2 METHYL 6 PHENYL 4 (2 PHENYLETHYNYL) 3,5 PYRIDINEDICARBOXYLIC ACID 5 BENZYL 3 ETHYL ESTER; 2 [4 (2 CARBOXYETHYL)PHENETHYLAMINO]ADENOSINE 5' (N ETHYLCARBOXAMIDE); 4 AMINO 5 (3 BROMOPHENYL) 7 (6 MORPHOLINO 3 PYRIDINYL)PYRIDO[2,3 D]PYRIMIDINE; 4 [2 [7 AMINO 2 (2 FURYL) 1,2,4 TRIAZOLO[2,3 A][1,3,5]TRIAZIN 5 YLAMINO]ETHYL]PHENOL; 5 IODOTUBERCIDIN; 6 ETHYL 2 PHENYL 4 PROPYL 3 PYRIDINECARBOXYLIC ACID 5 THIOCARBOXYLIC ACID 5 ETHYL 3 PROPYL ESTER; 6 N (2 HYDROXYCYCLOPENTYL)ADENOSINE; 9 CHLORO 2 (2 FURYL) 5 PHENYLACETYLAMINO 1,2,4 TRIAZOLO[1,5 C]QUINAZOLINE; ADENOSINE A2A RECEPTOR; ADENOSINE RECEPTOR; CAPADENOSON; EVODENOSON; GW 493838; ISTRADEFYLLINE; PARAXANTHINE; PENTOSTATIN; PICLIDENOSON; PRELADENANT; PURINERGIC P2X RECEPTOR; PURINERGIC P2Y RECEPTOR; PURINERGIC P2Y12 RECEPTOR; PURINERGIC P2Y2 RECEPTOR; REGADENOSON; ROLOFYLLINE; THEOPHYLLINE; TOZADENANT; TRABODENOSON; UK 432097; UNINDEXED DRUG; VIPADENANT; ADENOSINE RECEPTOR BLOCKING AGENT; ADENOSINE RECEPTOR STIMULATING AGENT; PURINERGIC P2Y RECEPTOR AGONIST; PURINERGIC RECEPTOR AFFECTING AGENT;

ALLOSTERISM; BRAIN INJURY; CHRONIC PAIN; CRYSTAL STRUCTURE; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; GLAUCOMA; HUMAN; HYPERSOMNIA; MUTAGENESIS; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NEUROPATHIC PAIN; NEUROPROTECTION; NONHUMAN; OPTIC NERVE DISEASE; PAIN; PARKINSON DISEASE; PERSISTENT ATRIAL FIBRILLATION; PRIORITY JOURNAL; REVIEW; ANIMAL; CHEMISTRY; MEDICINAL CHEMISTRY; METABOLISM; STRUCTURE ACTIVITY RELATION;

ANIMALS; CHEMISTRY, PHARMACEUTICAL; HUMANS; PURINERGIC AGENTS; PURINERGIC P1 RECEPTOR AGONISTS; PURINERGIC P1 RECEPTOR ANTAGONISTS; PURINERGIC P2Y RECEPTOR AGONISTS; RECEPTORS, PURINERGIC P1; RECEPTORS, PURINERGIC P2X; RECEPTORS, PURINERGIC P2Y; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84951309922     PISSN: 00283908     EISSN: 18737064     Source Type: Journal    
DOI: 10.1016/j.neuropharm.2015.12.001     Document Type: Review

References (192)

1. M. Al-Rashida, and J. Iqbal Therapeutic potentials of ecto-nucleoside triphosphate diphosphohydrolase, ecto-nucleotide pyrophosphatase/phosphodiesterase, ecto-5′-nucleotidase, and alkaline phosphatase inhibitors Med. Res. Rev. 34 2014 703 743
2. K. Alexander, W. Niforatos, B. Bianchi, E.C. Burgard, K.J. Lynch, E.A. Kowaluk, M.F. Jarvis, and T. van Biesen Allosteric modulation and accelerated resensitization of human P2X(3) receptors by cibacron blue J. Pharmacol. Exp. Ther. 291 1999 1135 1142
3. M.W. Alnouri, S. Jepards, A. Casari, A.C. Schiedel, S. Hinz, and C.E. Müller Selectivity is species-dependent: characterization of standard agonists and antagonists at human, rat, and mouse adenosine receptors Purinergic Signal 11 2015 389 407
4. J.M. Amatrudo, J.P. Olson, H.K. Agarwal, and G.C. Ellis-Davies Caged compounds for multichromic optical interrogation of neural systems Eur. J. Neurosci. 41 2015 5 16
5. R.D. Andó, B. Méhész, K. Gyires, P. Illes, and B. Sperlágh A comparative analysis of the activity of ligands acting at P2X and P2Y receptor subtypes in models of neuropathic, acute and inflammatory pain Br. J. Pharmacol. 159 2010 1106 1117
6. 2A adenosine receptor antagonists in the therapy of Parkinson's disease Pharmacol. Pharmacol. Ther. 132 2011 280 299
7. A.R. Ase, N.S. Honson, H. Zaghdane, T.A. Pfeifer, and P. Séguéla Identification and characterization of a selective allosteric antagonist of human P2X4 receptor channels Mol. Pharmacol. 87 2015 606 616
8. B. Balázs, T. Dankó, G. Kovács, L. Köles, M.A. Hediger, and A. Zsembery Investigation of the inhibitory effects of the benzodiazepine derivative, 5-BDBD on P2X4 purinergic receptors by two complementary methods Cell. Physiol. biochem. 32 2013 11 24
9. Y. Baqi Ecto-Nucleotidase inhibitors: recent developments in drug discovery Mini-Rev. Med. Chem. 15 2015 21 33
10. Y. Baqi, R. Hausmann, C. Rosefort, J. Rettinger, G. Schmalzing, and C.E. Müller Discovery of potent competitive antagonists and positive modulators of the P2X2 receptor J. Med. Chem. 54 2011 817 830
11. 14 receptor inhibits UDP-glucose-stimulated chemotaxis of human neutrophils Mol. Pharmacol. 84 2013 41 49
12. R. Bartlett, L. Stokes, and R. Sluyter The P2X7 receptor channel: recent developments and the Use of P2X7 antagonists in models of disease Pharmacol. Rev. 66 2014 638 675
13. D. Baudelet, E. Lipka, R. Millte, and A. Ghinet Involvement of the P2X7 purinergic receptor in inflammation: an update of antagonists series since 2009 and their promising therapeutic potential Curr. Med. Chem. 22 2015 713 729
14. S. Beggs, T. Trang, and M.W. Salter P2X4R+ microglia drive neuropathic pain Nat. Neurosci. 15 2012 1068 1073
15. T. Bele, and E. Fabbretti P2X receptors, sensory neurons and pain Curr. Med. Chem. 22 2015 845 850
16. L.P. Bernier, A.R. Ase, X. Tong, E. Hamel, D. Blais, Q. Zhao, D.E. Logothetis, and P. Séguéla Direct modulation of P2X1 receptor-channels by the lipid phosphatidylinositol 4,5-bisphosphate Mol. Pharmacol. 74 2008 785 792
17. L.P. Bernier, A.R. Ase, S. Chevallier, D. Blais, Q. Zhao, E. Boué-Grabot, D. Logothetis, and P. Séguéla Phosphoinositides regulate P2X4 ATP-gated channels through direct interactions J. Neurosci. 28 2008 12938 12945
18. L.P. Bernier, A.R. Ase, and P. Séguéla Post-translational regulation of P2X receptor channels: modulation by phospholipids Front. Cell. Neurosci. 7 2013 226
19. A. Bhattacharya, Q. Wang, H. Ao, J.R. Shoblock, B. Lord, L. Aluisio, I. Fraser, D. Nepomuceno, R.A. Neff, N. Welty, T.W. Lovenberg, P. Bonaventure, A.D. Wickenden, and M.A. Letavic Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567 Br. J. Pharmacol. 170 2013 624 640
20. S. Bhattarai, M. Freundlieb, J. Pippel, A. Meyer, A. Abdelrahman, A. Fiene, S.-Y. Lee, H. Zimmermann, G.G. Yegutkin, N. Sträter, A. El-Tayeb, and C.E. Müller β-Methylene-ADP (AOPCP) derivatives and analogues: development of potent and selective ecto-5′-nucleotidase (CD73) inhibitors J. Med. Chem. 58 2015 6248 6263
21. H. Bölcskei, and B. Farkas P2X3 and P2X2/3 receptor antagonists Pharm. Pat. Anal. 3 2014 53 64
22. 2 receptor heterotetramer Proc. Natl. Acad. Sci. U. S. A. 112 2015 E3609 E3618
23. 2B receptor antagonists and a new radioligand with subnanomolar affinity and subtype specificity J. Med. Chem. 52 2009 3994 4006
24. 1 receptor Mol. Pharmacol. 50 1996 1323 1329
25. A. Brunschweiger, and C.E. Müller P2 receptors activated by uracil nucleotides - an update Curr. Med. Chem. 13 2006 289 312
26. G. Burnstock Physiopathological roles of P2X receptors in the central nervous system Curr. Med. Chem. 22 2015 819 844
27. G. Burnstock, and F. Di Virgilio Purinergic Signalling and cancer Purinergic Signal 9 2013 491 540
28. G. Burnstock, and A. Verkhratsky Purinergic Signalling and the Nervous System 2012 Springer-Verlag Berlin Heidelberg 978-3-642-28862-3
29. 14 receptor Mol. Pharmacol. 76 2009 1341 1348
30. D.S. Carter, M. Alam, H. Cai, M.P. Dillon, A.P. Ford, J.R. Gever, A. Jahangir, C. Lin, A.G. Moore, P.J. Wagner, and Y. Zhai Identification and SAR of novel diaminopyrimidines. Part 1: the discovery of RO-4, a dual P2X(3)/P2X(2/3) antagonist for the treatment of pain. Bioorg Med. Chem. Lett. 19 2009 1628 1631
31. J.K. Chambers, L.E. Macdonald, H.M. Sarau, R.S. Ames, K. Freeman, J.J. Foley, Y. Zhu, M.M. McLaughlin, P. Murdock, L. McMillan, and et al. A G protein-coupled receptor for UDP-glucose J. Biol. Chem. 275 2000 10767 10771
32. L. Chang, S.Y. Lee, P. Leonczak, J. Rozenski, S. De Jonghe, T. Hanck, C.E. Müller, and P. Herdewijn Imidazopyridine- and purine-thioacetamide derivatives: potent inhibitors of nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) J. Med. Chem. 57 2014 10080 10100
33. 1 antagonists J. Med. Chem. 56 2013 1704 1714
34. T. Chataigneau, D. Lemoine, and T. Grutter Exploring the ATP-binding site of P2X receptors Front. Cell. Neurosci. 7 2013 273
35. J.F. Chen Adenosine receptor control of cognition in normal and disease Int. Rev. Neurobiol. 119 2014 257 307
36. J.F. Chen, H.K. Eltzschig, and B.B. Fredholm Adenosine receptors as drug targets - what are the challenges? Nat. Rev. Drug Disc. 12 2013 265 286
37. 13 receptors by conformational constraint of an ADP analogue J. Pharm. Exp. Ther. 311 2004 1038 1043
38. A.M. Choo, W.J. Miller, Y.C. Chen, P. Nibley, T.P. Patel, C. Goletiani, B. Morrison 3rd, M.K. Kutzing, B.L. Firestein, J.Y. Sul, P.G. Haydon, and D.F. Meaney Antagonism of purinergic signalling improves recovery from traumatic brain injury Brain 136 2013 65 80
39. C.C. Chrovian, C.J. Rech, A. Bhattacharya, and M.A. Letavic P2X7 antagonists as potential therapeutic agents for the treatment of CNS disorders Prog. Med. Chem. 53 2014 65 100
40. D.A. Cockayne, P.M. Dunn, Y. Zhong, W. Rong, S.G. Hamilton, G.E. Knight, H.Z. Ruan, B. Ma, P. Yip, P. Nunn, S.B. McMahon, G. Burnstock, and A.P. Ford P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP J. Physiol. 567 2005 621 639
41. C. Coddou, Z. Yan, T. Obsil, J.P. Huidobro-Toro, and S.S. Stojilkovic Activation and regulation of purinergic P2X receptor channels Pharmacol. Rev. 63 2011 641 683
42. C. Coddou, S.S. Stojilkovic, and J.P. Huidobro-Toro Allosteric modulation of ATP-gated P2X receptor channels Rev. Neurosci. 22 2011 335 354
43. M. Congreve, A.S. Doré, A. Jazayeri, and R. Nonoo Chapter 1 Scapin Multifaceted Roles of Crystallography in Modern Drug Discovery NATO Science for Peace and Security Series a: Chemistry and Biology 2015 Springer Science+Business Media Dordrecht 10.1007/978-94-017-9719-1-1
44. P.F. Corbelini, F. Figueiró, G.M. das Neves, S. Andrade, D.F. Kawano, A.M. Oliveira Battastini, and V.L. Eifler-Lima Insights into ecto-5′-nucleotidase as a new target for cancer therapy: a medicinal chemistry study Curr. Med. Chem. 22 2015 1776 1792
45. D. Dal Ben, M. Buccioni, C. Lambertucci, G. Marucci, A. Thomas, and R. Volpini Purinergic P2X receptors: structural models and analysis of ligand-target interaction Eur. J. Med. Chem. 89 2015 561 580
46. J.P. De Rivero Vaccari, D. Bastien, G. Yurcisin, I. Pineau, W.D. Dietrich, Y. De Koninck, R.W. Keane, and S. Lacroix P2X4 receptors influence inflammasome activation after spinal cord injury J. Neurosci. 32 2012 3058 3066
47. M. De Roo, J. Rodeau, and R. Schlichter Dehydroepiandrosterone potentiates native ionotropic ATP receptors containing the P2X2 subunit in rat sensory neurones J. Physiol. 552 2003 59 71
48. 1 receptor signaling mediates astrocytic hyperactivity in vivo in an Alzheimer's disease mouse model Nat. Commun. 5 2014 5422
49. F. Di Virgilio Liaisons dangereuses: P2X7 and the inflammasome Trends Pharmacol. Sci. 28 2007 465 472
50. F. Di Virgilio P2X receptors and inflammation Curr. Med. Chem. 22 2015 866 877
51. D. Donnelly-Roberts, S. McGaraughty, C.C. Shieh, P. Honore, and M.F. Jarvis Painful purinergic receptors J. Pharmacol. Exp. Ther. 324 2008 409 415
52. A.J. Duplantier, M.A. Dombroski, C. Subramanyam, A.M. Beaulieu, S.-P. Chang, C.A. Gabel, C. Jordan, A.S. Kalgutkar, K.G. Kraus, J.M. Labasi, C. Mussari, D.G. Perregaux, R. Shepard, T.J. Taylor, K.A. Trevena, C. Whitney-Pickett, and K. Yoon Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224,535 Bioorg. Med. Chem. Lett. 21 2011 3708 3711
53. 1 receptor activator in the gut Proc. Natl. Acad. Sci. U. S. A. 111 2014 15821 15826
54. 11 receptor Biochem. J. 409 2008 107 116
55. S. El-Ajouz, D. Ray, R.C. Allsopp, and R.J. Evans Molecular basis of selective antagonism of the P2X1 receptor for ATP by NF449 and suramin: contribution of basic amino acids in the cysteine-rich loop Br. J. Pharmacol. 165 2012 390 400
56. 1 adenosine receptor agonists and their potential therapeutic applications Exp. Opin. Investig. Drugs 17 2008 1901 1910
57. L.K. Farmer, R. Schmid, and R.J. Evans Use of chimeras, point mutants, and molecular modeling to map the antagonist-binding site of 4,4′,4″,4a (carbonylbis-(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakisbenzene-1,3-disulfonic acid (NF449) at P2X1 receptors for ATP J. Biol. Chem. 290 2015 1559 1569
58. S. Ferré, V. Casadó, L.A. Devi, M. Filizola, R. Jockers, M.J. Lohse, G. Milligan, J.P. Pin, and X. Guitart G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives Pharmacol. Rev. 66 2014 413 434
59. 3AR) agonists Drug Disc, Today 17 2012 359 366
60. A.P. Ford In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization Purinergic Signal. 8 2012 3 26
61. A.P. Ford, J.R. Gever, P.A. Nunn, Y. Zhong, J.S. Cefalu, M.P. Dillon, and D.A. Cockayne Purinoceptors as therapeutic targets for lower urinary tract dysfunction Br. J. Pharmacol. 147 2 2006 132 143
62. A.P. Ford, and B.J. Undem The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders Front. Cell. Neurosci. 7 2013 267 10.3389/fncel.2013.00267
63. 1 adenosine receptor with antinociceptive effects in mice J. Med. Chem. 52 2009 2393 2406
64. 1 receptor signaling without affecting nucleotide binding Biochem. Pharmacol. 68 2004 231 237
65. 12 receptors for light-directed facilitation of platelet aggregation Biochem. Pharmacol. 75 2008 1341 1347
66. 3 adenosine receptor agonist efficacy and potency by imidazoquinolinamine allosteric enhancers Biochem. Pharmacol. 82 2011 658 668
67. M. Gao, M. Wang, M.A. Green, G.D. Hutchins, and Q.-H. Zheng Synthesis of [3H]GSK1482160 as a new PET agent for targeting P2X7 receptor Bioorg. Med. Chem. Lett. 25 2015 1965 1970
68. J.R. Gever, D.A. Cockayne, M.P. Dillon, G. Burnstock, and A.P. Ford Pharmacology of P2X channels Pflugers Arch. 452 2006 513 537
69. J.R. Gever, R. Soto, R.A. Henningsen, R.S. Martin, D.H. Hackos, S. Panicker, W. Rubas, I.B. Oglesby, M.P. Dillon, M.E. Milla, G. Burnstock, and A.P. Ford AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist Br. J. Pharmacol. 160 2010 1387 1398
70. 1 receptors mediate local anti-nociceptive effects of acupuncture Nat. Neurosci. 13 2010 883 888
71. L. Grimes, and M.T. Young Purinergic P2X receptors: structural and functional features depicted by X-ray and molecular modelling studies Curr. Med. Chem. 22 2015 783 798
72. H. Gunosewoyo, and M. Kassiou P2X purinergic receptor ligands: recently patented compounds Expert Opin. Ther. Pat. 2010 20 2010 625 646
73. H. Gunosewoyo, M.J. Coster, M.R. Bennett, and M. Kassiou Purinergic P2X7 receptor antagonists: chemistry and fundamentals of biological screening Bioorg. Med. Chem. Lett. 2009 17 2009 4861 4865
74. 11 receptor Biochem. Pharmacol. 86 2013 645 655
75. 6 receptor protects against death-receptor mediated glial apoptosis Neurosci. Lett. 578 2014 80 84
76. M. Hattori, and E. Gouaux Molecular mechanism of ATP binding and ion channel activation in P2X receptors Nature 485 2012 207 212
77. R. Hausmann, and G. Schmalzing P2X1 and P2X2 receptors in the central nervous system as possible drug targets CNS Neurol. Disord. Drug Targets 11 2012 675 686
78. R. Hausmann, A. Kless, and G. Schmalzing Key sites for P2X receptor function and multimerization: overview of mutagenesis studies on a structural basis Curr. Med. Chem. 22 2015 799 818
79. 12 receptor regulates microglial activation by extracellular nucleotides Nat. Neurosci. 9 2006 1512 1519
80. B. Hechler, and C. Gachet P2 receptors and platelet function Purinergic Signal. 7 2011 293 303
81. V. Hernandez-Olmos, A. Abdelrahman, A. El-Tayeb, D. Freudendahl, S. Weinhausen, and C.E. Müller N-substituted phenoxazine and acridone derivatives: structure-activity relationships of potent P2X4 receptor antagonists J. Med. Chem. 55 2012 9576 9588
82. C.L. Herold, A.D. Qi, T.K. Harden, and R.A. Nicholas Agonist versus antagonist action of ATP at the P2Y4 receptor is determined by the second extracellular loop J. Biol. Chem. 279 2004 11456 11464
83. 2B receptors J. Pharmacol. Exp. Ther. 349 2014 427 436
84. 12-receptor J. Thromb. Haemost. 12 2014 1898 1905
85. 12 receptor blockade alleviates inflammatory and neuropathic pain and cytokine production in rodents Neurobiol. Dis. 70 100 2014 162 178
86. 2A adenosine receptor bound to an antagonist Science 322 2008 1211 1217
87. 1-adenosine receptors J. Med. Chem. 32 1989 1043 1051
88. K.A. Jacobson, Y.C. Kim, S.S. Wildman, A. Mohanram, T.K. Harden, J.L. Boyer, B.F. King, and G. Burnstock A pyridoxine cyclic phosphate and its 6-azoaryl derivative selectively potentiate and antagonize activation of P2X1 receptors J. Med. Chem. 41 1998 2201 2206
89. K.A. Jacobson, S. Paoletta, V. Katritch, B. Wu, Z.G. Gao, Q. Zhao, R.C. Stevens, and E. Kiselev Nucleotides acting at P2Y receptors: Connecting structure and function Mol. Pharmacol. 88 2015 220 230
90. A. Jahangir, M. Alam, D.S. Carter, M.P. Dillon, D.J. Bois, A.P. Ford, J.R. Gever, C. Lin, P.J. Wagner, Y. Zhai, and J. Zira Identification and SAR of novel diaminopyrimidines. Part 2: the discovery of RO-51, a potent and selective, dual P2X(3)/P2X(2/3) antagonist for the treatment of pain Bioorg. Med. Chem. Lett. 19 2009 1632 1635
91. S. Jaime-Figueroa, R. Greenhouse, F. Padilla, M.P. Dillon, J.R. Gever, and A.P. Ford Discovery and synthesis of a novel and selective drug-like P2X(1) antagonist Bioorg. Med. Chem. Lett. 15 2005 3292 3295
92. J. Jankowski, V. Jankowski, B. Seibt, L. Henning, W. Zidek, and H. Schlüter Identification of dinucleoside polyphosphates in adrenal glands Biochem. Biophys. Res. Commun. 304 2003 365 370
93. V. Jankowski, M. Tölle, R. Vanholder, G. Schönfelder, M. van der Giet, L. Henning, H. Schlüter, M. Paul, W. Zidek, and J. Jankowski Uridine adenosine tetraphosphate: a novel endothelium- derived vasoconstrictive factor Nat. Med. 11 2005 223 227
94. V. Jankowski, M. van der Giet, H. Mischak, M. Morgan, W. Zidek, and J. Jankowski Dinucleoside polyphosphates: strong endogenous agonists of the purinergic system Br. J. Pharmacol. 157 2009 1142 1153
95. M.F. Jarvis Contributions of P2X3 homomeric and heteromeric channels to acute and chronic pain Expert Opin. Ther. Targets 7 2003 513 522
96. M.F. Jarvis, E.C. Burgard, S. McGaraughty, P. Honore, K. Lynch, T.J. Brennan, A. Subieta, T. Van Biesen, J. Cartmell, B. Bianchi, W. Niforatos, K. Kage, H. Yu, J. Mikusa, C.T. Wismer, C.Z. Zhu, K. Chu, C.H. Lee, A.O. Steward, J. Polakowski, B.F. Cox, E. Kowaluk, M. Williams, J. Sullivan, and C. Faltynek A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat Proc. Natl. Acad. Sci. U. S. A. 99 2002 17179 17184
97. 6 receptors J. Med. Chem. 57 2014 3874 3883
98. 3 receptor antagonist J. Med. Chem. 50 2007 4543 4547
99. M.U. Kassack, K. Braun, M. Ganso, H. Ullmann, P. Nickel, B. Böing, G. Müller, and G. Lambrecht Structure-activity relationships of analogues of NF449 confirm NF449 as the most potent and selective known P2X1 receptor antagonist Eur. J. Med. Chem. 39 2004 345 357
100. T. Kawate, J.C. Michel, W.T. Birdsong, and E. Gouaux Crystal structure of the ATP-gated P2X4 ion channel in the closed state Nature 460 2009 592 598
101. P.A. Kemp, R.A. Sugar, and A.D. Jackson Nucleotide-mediated mucin secretion from differentiated human bronchial epithelial cells Am. J. Respir. Cell Mol. Biol. 31 2004 446 455
102. 4 receptor Mol. Pharmacol. 57 2000 926 931
103. E.C. Keystone, M.M. Wang, M. Layton, S. Hollis, and I.B. McInnes Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active disease despite treatment with methotrexate or sulphasalazine Ann. Rheum. Dis. 71 2012 1630 1635
104. B.F. King, I.D. Knowles, G. Burnstock, and A.G. Ramage Investigation of the effects of P2 purinoceptor ligands on the micturition reflex in female urethane-anaesthetized rats Br. J. Pharmacol. 142 2004 519 530
105. 14 receptor antagonist molecular probes ACS Chem. Biol. 9 2014 2833 2842
106. 14 receptor Bioorg. Med. Chem. Lett. 25 2015 4733 4739
107. 1 receptor mediated nitric oxide production Neuropsychopharmacol 28 2003 435 444
108. 3 receptor Eur. J. Pharmacol. 556 1-3 2007 14 18
109. 6 receptors is a novel mediator of microglial phagocytosis Nature 446 2007 1091 1095
110. 1 receptor agonists with antinociceptive effects in mice J. Med. Chem. 55 2012 6467 6477
111. E.A. Kowaluk, J. Mikusa, C.T. Wismer, C.Z. Zhu, E. Schweitzer, J.J. Lynch, and et al. ABT-702 (4-amino-5-(3-bromophenyl)-7-(6- morpholino-pyridin- 3-yl)pyrido[2,3-d]pyrimidine), a novel orally effective adenosine kinase inhibitor with analgesic and anti-inflammatory properties. II. In vivo characterization in the rat J. Pharmacol. Exp. Ther. 295 2000 1165 1174
112. E. Kozma, P.S. Jayasekara, L. Squarcialupi, S. Paoletta, S. Moro, S. Federico, G. Spalluto, and K.A. Jacobson Fluorescent ligands for adenosine receptors Bioorg. Med. Chem. Lett. 23 2013 26 36
113. 3 adenosine receptor J. Pharmacol. Exp. Ther. 317 2006 172 180
114. U. Lalo, A. Verkhratsky, and Y. Pankratov Ivermectin potentiates ATP-induced ion currents in cortical neurones: evidence for functional expression of P2X4 receptors? Neurosci. Lett. 421 2007 158 162
115. C. Lambertucci, D. Dal Ben, M. Buccioni, G. Marucci, A. Thomas, and R. Volpini Medicinal chemistry of P2X receptors: agonists and orthosteric antagonists Curr. Med. Chem. 22 2015 915 928
116. E.R. Lazarowski, W.C. Watt, M.J. Stutts, R.C. Boucher, and T.K. Harden Pharmacological selectivity of the cloned human P2U-purinoceptor: potent activation by diadenosine tetraphosphate Br. J. Pharmacol. 116 1995 1619 1627
117. 2A receptor Mol. Pharmacol. 87 2015 907 915
118. S.Y. Lee, A. Fienem, W. Li, T. Hanck, K.A. Brylev, V.E. Fedorov, J. Lecka, A. Haider, H.J. Pietzsch, H. Zimmermann, J. Sévigny, U. Kortz, H. Stephan, and C.E. Müller Polyoxometalates - potent and selective ecto-nucleotidase inhibitors Biochem. Pharmacol. 93 2015 171 181
119. R.D. Leone, Y.C. Lo, and J.D. Powell A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy Comput. Struct. Biotechnol. J. 13 2015 265 272
120. M.A. Letavic, B. Lord, F. Bischoff, N.A. Hwryluk, S. Pieters, J.Z. Sales, A.I. Velter, H. Ao, P. Bonaventure, V. Contreras, X. Jiang, K.L. Morton, B. Scott, Q. Wang, A.D. Wickenden, N.I. Carruthers, and A. Bhattacharya Synthesis and pharmacological characterization of two novel penetrating P2X7 antagonists ACS Med. Chem. Lett. 12 2013 419 422
121. 3 adenosine receptor antagonists J. Med. Chem. 41 1998 3186 3201
122. 3 receptor activation selectively alleviates persistent pain states Brain 138 2015 28 35
123. W. Liu, E. Chun, A.A. Thompson, P. Chubukov, F. Xu, V. Katritch, G.W. Han, C.B. Roth, L.H. Heitman, A.P. IJzerman, V. Cherezov, and R.C. Stevens Structural basis for allosteric regulation of GPCRs by sodium ions Science 337 2012 232 236
124. L.C. Loram, J.A. Harrison, E.M. Sloane, M.R. Hutchinson, P. Sholar, F.R. Taylor, and et al. Enduring reversal of neuropathic pain by a single intrathecal injection of adenosine 2A receptor agonists: a novel therapy for neuropathic pain J. Neurosci. 29 2009 14015 14025
125. B. Lord, L. Aluisio, J.R. Shoblock, R.A. Neff, E.I. Varlinskaya, M. Ceusters, T.W. Lovenberg, N. Carruthers, P. Bonaventure, M.A. Letavic, T. Deak, W. Drinkenburg, and A. Bhattacharya Pharmacology of a novel central nervous system-penetrant P2X7 antagonist JNJ-42253432 J. Pharmacol. Exp. Ther. 351 2014 628 641
126. 3H]JNJ-54232334 Eur. J. Pharmacol. 765 2015 551 559
127. 1 receptor agonist, alleviates neuropathic pain in mice through functional glial and microglial changes without affecting Motor or cardiovascular functions Molecules 17 2012 13712 13726
128. G. Magni, and S. Ceruti P2Y purinergic receptors: new targets for analgesic and antimigraine drugs Biochem. Pharmacol. 85 2013 466 477
129. M. Malmsjö, M. Hou, W. Pendergast, D. Erlinge, and L. Edvinsson The stable pyrimidines UDPβS and UTPγS discriminate between contractile cerebrovascular P2 receptors Eur. J. Pharmacol. 458 2003 305 311
130. 6 nucleotide receptors Biochem. Pharmacol. 67 2004 1763 1770
131. N. Mehta, M. Kaur, M. Singh, S. Chand, B. Vyas, P. Silakari, M.S. Bahia, and O. Silakari Purinergic receptor P2X : a novel target for anti-inflammatory therapy Bioorg. Med. Chem. Lett. 22 2014 54 88
132. 11 agonist and stimulates release of interleukin-8 from human monocyte-derived dendritic cells J. Pharmacol. Exp. Ther. 332 2011 238 247
133. K.J. Miller, A.D. Michel, I.P. Chessell, and P.P. Humphrey Cibacron blue allosterically modulates the rat P2X4 receptor Neuropharmacology 37 1998 1579 1586
134. G. Mo, L.P. Bernier, Q. Zhao, A.J. Chabot-Doré, A.R. Ase, D. Logothetis, C.Q. Cao, and P. Séguéla Subtype-specific regulation of P2X3 and P2X2/3 receptors by phosphoinositides in peripheral nociceptors Mol. Pain 5 2009 47
135. C.E. Müller Emerging structures and ligands for P2X3 and P2X4 receptors-towards novel treatments of neuropathic pain Purinergic Signal 6 2010 145 148
136. C.E. Müller Medicinal chemistry of P2X receptors: allosteric modulators Curr. Med. Chem. 22 2015 929 941
137. C.E. Müller, and K.A. Jacobson Recent developments in adenosine receptor ligands and their potential as novel drugs Biochem. Biophys. Acta - Biomembr. 1808 2011 1290 1308
138. C.E. Müller, A.C. Schiedel, and Y. Baqi Allosteric modulators of rhodopsin-like G protein-coupled receptors: opportunities in drug development Pharmacol. Ther. 135 2012 292 315
139. K. Mulryan, D.P. Gitterman, C.J. Lewis, C. Vial, B.J. Leckie, A.L. Cobb, J.E. Brown, E.C. Conley, G. Buell, C.A. Pritchard, and R.J. Evans Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors Nature 403 2000 86 89
140. K. Nagata, T. Imai, T. Yamashita, M. Tsuda, H. Tozaki-Saitoh, and K. Inoue Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief Mol. Pain 5 2009 20 10.1186/1744-8069-5-20
141. G. Navarro, D.O. Borroto-Escuela, K. Fuxe, and R. Franco Purinergic signaling in Parkinson's disease Relevance Treat. Neuropharmacol. 104 2015 161 168 10.1016/j.neuropharm.2015.07.024
142. A. Nicke, H.G. Baumert, J. Rettinger, A. Eichele, G. Lambrecht, E. Mutschler, and G. Schmalzing P2X1 and P2X3 receptors form stable trimers: a novel structural motif of ligand-gated ion channels EMBO J. 17 1998 3016 3028
143. W. Nörenberg, H. Sobottka, C. Hempel, T. Plötz, W. Fischer, G. Schmalzing, and M. Schaefer Positive allosteric modulation by ivermectin of human but not murine P2X7 receptors Br. J. Pharmacol. 167 2012 48 66
144. F. Ochoa-Cortes, A. Liñán-Rico, K.A. Jacobson, and F.L. Christofi Potential for developing purinergic drugs for gastrointestinal diseases Inflamm. Bowel Dis. 20 2014 1259 1287
145. 3H]PSB-0413 Purinergic Signal 9 2013 59 66
146. M. Okuro, N. Fujiki, N. Kotorii, Y. Ishimaru, P. Sokoloff, and S. Nishino Effects of paraxanthine and caffeine on sleep, Locomotor activity, and body temperature in Orexin/Ataxin-3 Transgenic Narcoleptic mice Sleep 33 7 2010 930 942
147. S. Omura, and A. Crump The life and times of ivermectin - a success story Nat. Rev. Microbiol. 2 2004 984 989
148. O. Ostrovskaya, L. Asatryan, L. Wyatt, M. Popova, K. Li, R.W. Peoples, R.L. Alkana, and D.L. Davies Ethanol is a fast channel inhibitor of P2X4 receptors J. Pharmacol. Exp. Ther. 337 2011 171 179
149. 3 adenosine receptor-selective nucleosides as pharmacological tools to study chronic neuropathic pain J. Med. Chem. 56 2013 5949 5963
150. 12 receptor in light of X-ray structural information J. Computer-Aided Mol. Des. 29 2015 737 756
151. K. Puchałowicz, M. Tarnowski, I. Baranowska-Bosiacka, D. Chlubek, and V. Dziedziejko P2X and P2Y Receptors - Role in the Pathophysiology of the Nervous System Int. J. Mol. Sci. 15 2014 23672 23704
152. J. Rettinger, G. Schmalzing, S. Damer, G. Müller, P. Nickel, and G. Lambrecht The suramin analogue NF279 is a novel and potent antagonist selective for the P2X(1) receptor Neuropharmacology 39 2000 2044 2053
153. M. Rivera-Oliver, and M. Díaz-Ríos Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: a review Life Sci. 101 2014 1 9
154. 14 Bioorg. Med. Chem. Lett. 21 2011 4366 4368
155. D.A. Rudolph, J. Alcazar, M.K. Ameriks, A.B. Anton, H. Ao, P. Bonaventure, N.I. Carruther, C.C. Chrovian, M. De Angelis, B. Lord, J.C. Rech, Q. Wang, A. Bhattacharya, J.I. Andres, and M.A. Letavic Novel methyl substituted 1-(5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)methanones are P2X7 antagonists Bioorg. Med. Chem. Lett. 25 2015 3157 3163
156. 1 receptor partial agonists in neuropathic pain Eur. J. Pharmacol. 514 2005 131 140
157. 1 receptors, sleep Deprivation, Imipramine, and Ketamine inhibit Depressive-like Behavior via Induction of Homer1a Neuron 87 2015 549 562
158. C.J. Sharp, A.J. Reeve, S.D. Collins, J.C. Martindale, S.G. Summerfield, B.S. Sargent, and et al. Investigation into the role of P2X3/P2X2/3 receptors in neuropathic pain following chronic constriction injury in the rat: an electrophysiological study Br. J. Pharmacol. 148 2006 845 851
159. S.R. Shaver, J.L. Rideout, W. Pendergast, J.G. Douglass, E.G. Brown, J.L. Boyer, R.I. Patel, C.C. Redick, A.C. Jones, M. Picher, and et al. Structure-activity relationships of dinucleotides: potent and selective agonists of P2Y receptors Purinergic Signal 1 2005 183 191
160. 2A-Adenosine receptor reserve for coronary vasodilation Circulation 98 1998 711 718
161. J.A. Sim, and R.A. North Amitriptyline does not block the action of ATP at human P2X4 receptor Br. J. Pharmacol. 160 2010 88 92
162. F. Soto, G. Lambrecht, P. Nickel, W. Stühmer, and A.E. Busch Antagonistic properties of the suramin analogue NF023 at heterologously expressed P2X receptors Neuropharmacology 38 1999 141 149
163. 12 receptor antagonist for the prevention of thrombosis Bioorg. Med. Chem. Lett. 17 2007 6013 6018
164. T.C. Stock, B.J. Bloom, N. Wei, S. Ishaq, W. Park, X. Wang, P. Gupta, and C.A. Mebus Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate J. Rheumatol. 39 2012 720 727
165. L.A. Stoddart, L.E. Kilpatrick, S.J. Briddon, and S.J. Hill Probing the pharmacology of G protein-coupled receptors with fluorescent ligands Neuropharmacology 2015 98, 48-57 http://dx.doi.org/10.1016/j.neuropharm.2015.04.033
166. M. Tendera, E. Gaszewska-Zurek, Z. Parma, P. Ponikowski, E. Jankowska, K. Kawecka-Jaszcz, D. Czarnecka, M. Krzemińska-Pakuła, Z. Bednarkiewicz, M. Sosnowski, M. Ochan Kilama, and R. Agrawal The new oral adenosine A1 receptor agonist capadenoson in male patients with stable angina Clin. Res. Cardiol. 101 7 2012 585 591
167. M. Tian, A. Abdelrahman, S. Weinhausen, S. Hinz, S. Weyer, S. Dosa, A. El-Tayeb, and C.E. Müller Carbamazepine derivatives with P2X4 receptor-blocking activity Bioorg. Med. Chem. 22 2014 1077 1088
168. 3 adenosine receptor-selective nucleosides: combination of 2-arylethynyl and bicyclo[3.1.0]hexane substitutions J. Med. Chem. 55 2012 4847 4860
169. 1 adenosine receptor activation by truncated (N)-methanocarba nucleosides: receptor docking and potent anticonvulsant activity J. Med. Chem. 55 2012 8075 8090
170. 3 adenosine receptor agonists J. Med. Chem. 57 2014 9901 9914
171. 3 adenosine receptor agonist that protects against chronic neuropathic pain Purinerg. Signal 11 2015 371 387
172. C.A. Trujillo, A.A. Nery, A.H. Martins, P. Majumder, F.A. Gonzalez, and H. Ulrich Inhibition mechanism of the recombinant rat P2X(2) receptor in glial cells by suramin and TNP-ATP Biochemistry 45 2006 224 233
173. 14 receptor: a template for structure-based design of selective agonist ligands Bioorg. Med. Chem. 23 2015 4056 4064
174. M. Tsuda, Y. Shigemoto-Mogami, S. Koizumi, A. Mizokoshi, S. Kohsaka, M.W. Salter, and K. Inoue P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury Nature 424 2003 778 783
175. L. Ulmann, F. Levavasseur, E. Avignone, R. Peyroutou, H. Hirbec, E. Audinat, and F. Rassendren Involvement of P2X4 receptors in hippocampal microglial activation after status epilepticus Glia 61 2013 1306 1319
176. 3 adenosine receptor Mol. Pharmacol. 45 1994 1101 1111
177. R. Varma, Y. Chai, J. Troncoso, J. Gu, H. Xing, S.S. Stojilkovic, M.P. Mattson, and N.J. Haughey Amyloid-beta induces a caspase-mediated cleavage of P2X4 to promote purinotoxicity Neuromolecular Med. 11 2009 63 75
178. 1 adenosine receptor allosteric modulator, exhibits anti-nociceptive properties in acute and neuropathic pain models in mice Neuropharmacology 81 2014 6 14
179. 1 receptor Mol. Pharmacol. 65 2004 426 436 Erratum in: Mol Pharmacol. 2004 65, 811
180. G.A. Weisman, L.T. Woods, L. Erb, and C.I. Seye P2Y receptors in the mammalian nervous system: pharmacology, ligands and therapeutic potential CNS Neurol. Disord. Drug Targets 11 6 2012 722 738
181. 2 receptor and cross-communication to the PDGF receptor Biochem. Biophys. Res. Commun. 417 2012 1035 1040
182. S.M. Wilkinson, H. Gunosewoyo, M.L. Barron, A. Boucher, M. McDonnel, P. Turner, D.E. Morrison, M.R. Bennett, I.S. McGregor, L.M. Rendina, and M. Kassiou The first CNS-active carborane: a novel P2X7 receptor antagonist with antidepressant activity ACS Chem. Neurosci. 21 2014 335 339
183. C. Wolf, C. Rosefort, G. Fallah, M.U. Kassack, A. Hamacher, M. Bodnar, H. Wang, P. Illes, A. Kless, G. Bahrenberg, G. Schmalzing, and R. Hausmann Molecular determinants of potent P2X2 antagonism identified by functional analysis, mutagenesis, and homology docking Mol. Pharmacol. 79 2011 649 661
184. 2A adenosine receptor Science 332 2011 322 327
185. S. Yelovitch, J. Camden, G.A. Weisman, and B. Fischer Boranophosphate isoster controls P2Y-receptor subtype selectivity and metabolic stability of dinucleoside polyphosphate analogues J. Med. Chem. 55 2012 437 448
186. C.L. Yi, Y.W. Liu, K.M. Xiong, R.R. Stewart, R.W. Peoples, X. Tian, L. Zhou, Y.X. Ai, Z.W. Li, Q.W. Wang, and C.Y. Li Conserved extracellular cysteines differentially regulate the inhibitory effect of ethanol in rat P2X4 receptors Biochem. Biophys. Res. Commun. 381 2009 102 106
187. H. Zemkova, V. Tvrdonova, A. Bhattacharya, and M. Jindrichova Allosteric modulation of ligand gated ion channels by ivermectin Physiol. Res. 63 2014 S215 S224
188. 12 receptor in complex with an antithrombotic drug Nature 509 2014 115 118
189. 12R receptor Nature 509 2014 119 122
190. 1 receptor Nature 520 2015 317 321
191. H. Zimmermann, M. Zebisch, and N. Sträter Cellular function and molecular structure of ecto-nucleotidases Purinergic Signal 8 2012 437 502
192. M.J. Zylka Pain-relieving prospects for adenosine receptors and ectonucleotidases Trends Mol. Med. 17 2011 188 196