2-Triazole-substituted adenosines: A new class of selective A3 adenosine receptor agonists, partial agonists, and antagonists

Journal of Medicinal Chemistry

Volumn 49, Issue 25, 2006, Pages 7373-7383

  Cosyn, Liesbet ^a   Palaniappan, Krishnan K ^b   Kim, Soo Kyung ^b   Duong, Heng T ^b   Gao, Zhan Guo ^b   Jacobson, Kenneth A ^b   Van Calenbergh, Serge ^a  

^a GHENT UNIVERSITY   (Belgium)

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

Author keywords

[No Author keywords available]

Indexed keywords

1 DEOXY 1 (6 METHYLAMINO 2 IODO 9H PURIN 9 YL) 2,3 O ISOPROPYLIDENE BETA DEXTRO RIBOFURANURONIC ACID; 2 (1 BENZYL 1,2,3 TRIAZOL 4 YL) N 6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; 2 (1,2,3 TRIAZOLYL)ADENOSINE DERIVATIVE; 2 (4 BUTYL 1,2,3 TRIAZOL 1 YL) 9 (5 ETHYLCARBAMOYL BETA DEXTRO RIBOFURANOSYL) N6 METHYLADENINE; 2 (4 BUTYL 1,2,3 TRIAZOL 1 YL) N6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; 2 (4 CYCLOHEXYLMETHYL 1,2,3 TRIAZOL 1 YL) N6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; 2 (4 CYCLOPENTYLMETHYL 1,2,3 TRIAZOL 1 YL) 9 (5 ETHYLCARBAMOYL BETA DEXTRO RIBOFURANOSYL) N6 METHYLADENINE; 2 (4 CYCLOPENTYLMETHYL 1,2,3 TRIAZOL 1 YL) N6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; 2 (4 DIMETHYLAMINOMETHYL 1,2,3 TRIAZOL 1 YL) N6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; 2 (4 ETHYL 1,2,3 TRIAZOL 1 YL) N6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; 2 [1 (3 METHOXYBENZYL) 1,2,3 TRIAZOL 4 YL)] N6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; 2 [4 (2 HYDROXYETHYL) 1,2,3 TRIAZOL 1 YL] N6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; 2 AZIDO 9 (5 ETHYLCARBAMOYL BETA DEXTRO RIBOFURANOSYL) N6 METHYLADENINE; 2 AZIDO N6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; 2 ETHYNYL N 6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL)PURINE; 9 (5 ETHYLCARBAMOYL BETA DEXTRO RIBOFURANOSYL) 2 IODO N6 METHYLADENINE; 9 (5 ETHYLCARBAMOYL BETA DEXTRO RIBOFURANOSYL) N6 METHYL 2 (1,2,3 TRIAZOL 1 YL)ADENINE; 9 (5 ETHYLCARBAMOYL BETA DEXTRO RIBOFURANOSYL) N6 METHYL 2 (4 BENZYL 1,2,3 TRIAZOL 1 YL)ADENINE; 9 (5 ETHYLCARBAMOYL BETA DEXTRO RIBOFURANOSYL) N6 METHYL 2 (4 PYRIDIN 2 YL 1,2,3 TRIAZOL 1 YL)ADENINE; ADENOSINE A3 RECEPTOR AGONIST; ADENOSINE A3 RECEPTOR ANTAGONIST; N6 (5 CHLORO 2 METHOXYBENZYL) 2 (4 CYCLOPENTYLMETHYL 1,2,3 TRIAZOL 1 YL) 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; N6 METHYL 2 (4 BENZYL 1,2,3 TRIAZOL 1 YL) 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; N6 METHYL 2 (4 PHENYL 1,2,3 TRIAZOL 1 YL) 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; N6 METHYL 2 (4 PYRIDIN 2 YL 1,2,3 TRIAZOL 1 YL) 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; N6 METHYL 2 [4 (4 PROPOXYPHENYL) 1,2,3 TRIAZOL 1 YL] 9 (BETA DEXTRO RIBOFURANOSYL)ADENINE; N6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL) 2 (1,2,3 TRIAZOL 1 YL)ADENINE; N6 METHYL 9 (BETA DEXTRO RIBOFURANOSYL) 2 [2 TRIMETHYLSILYLETHYN 1 YL]ADENINE; UNINDEXED DRUG;

ANIMAL CELL; ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; NONHUMAN; REACTION ANALYSIS;

ADENOSINE; ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; CYCLIC AMP; HUMANS; MODELS, MOLECULAR; RADIOLIGAND ASSAY; RECEPTOR, ADENOSINE A3; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZOLES;

EID: 33845481152     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0608208     Document Type: Article

References (50)

1. Müller, C. E. Adenosine receptor ligands. Recent developments. Part I. Agonists. Curr. Top. Med. Chem. 2000, 7, 1269-1288.
2. 3 receptors: pharmacological properties, species differences and receptor functions. Trends Pharmacol. Sci. 1994, 15, 298-306.
3. Fredholm, B. B.; Uzerman, A. P.; Jacobson, K. A.; Klotz, K. N.; Linden, J. International Union of Pharmacology XXV. Nomenclature and classification of adenosine receptors Pharmacol. Rev. 2001, 53, 527-552.
4. Jacobson, K. A.; Gao, Z-G. Adenosine receptors as therapeutic targets. Nat. Rev. Drug Discovery 2006, 5, 247-246.
5. 3 receptor subtype. Curr. Top. Med. Chem. 2003, 3, 463-469.
6. 3 adenosine receptor as a new target for cancer therapy and chemoprotection. Exp. Cell Res. 2001, 269, 230-236.
7. 3 receptor ligands. Curr. Top. Med. Chem. 2003, 3, 445-462.
8. 3 adenosine receptors: Protective vs. damaging effects identified using novel agonists and antagonists. Drug Dev. Res. 1998, 45, 113-124.
9. 3 adenosine receptor effects cell cycle progression and cell growth. Naunyn-Schmiedeberg's Arch. Pharmacol. 2000, 361, 225-234.
10. 3 receptor stimulation and cerebral ischemia. Eur. J. Pharmacol. 1994, 263, 59-67.
11. 3 adenosine receptor stimulation on seizures in mice. Eur. J. Pharmacol. 1995, 275, 23-29.
12. 3 antagonists. PCT Int. Appl. WO 2004000224, 2003.
13. Civan, M. M.; Macknight, A. D. C. The ins and outs of aqueous humour secretion. Exp. Eye Res. 2004, 78, 625-631.
14. 3 receptor ligands: New potential therapy for the treatment of glaucoma. Bioorg. Med. Chem. Lett. 2004, 14, 3775-3779.
15. 3 adenosine-receptor antagonist MRS 1292 inhibits adenosine-triggered human nonpigmented ciliary epithelial cell fluid release and reduces mouse intraocular pressure. Curr. Eye Res. 2005, 30, 747-754.
16. Poulsen, S. A.; Quinn, R. J. Adenosine receptors: New opportunities for future drugs. Bioorg. Med. Chem. 1998, 6, 619-641.
17. 3 adenosine receptor antagonists. J. Med. Chem. 2005, 48, 4910-4918.
18. 3 adenosine receptor antagonists. Synthesis, pharmacological evaluation, and ligand-receptor modeling studies. J. Med. Chem. 2006, 49, 3916-3925.
19. 3 adenosine receptor activation: Nucleoside ligands at the agonist/antagonist boundary. J. Med. Chem. 2002, 45, 4471-4484.
20. 3 adenosine receptors. Biochem. Pharmacol. 2003, 65, 1675-1684.
21. 3 adenosine aeceptor. Bioorg. Med. Chem. Lett. 2001, 11, 1931-1934.
22. 3 receptor agonists. J. Med. Chem. 2004, 47, 4766-4773.
23. 2B ligands. J. Med. Chem. 2002, 45, 3271-3279.
24. Lewis, W. G.; Green, L. G.; Grynszpan, F.; Radić, Z.; Carlier, P. R.; Taylor, P.; Finn, M. G.; Sharpless, K. B. Click chemistry in situ: acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks. Angew. Chem., Int. Ed. 2002, 41, 1053-1057.
25. (a) Alvarez, R.; Velázquez, S.; San-Félix, A.; Aquaro, S.; De Clercq, E.; Perno, C.-F.; Karlsson, A.; Balzarini, J.; Camarassa, M. J. 1,2,3-Triazol-[2′,5′-bis-O-(tert-butyldimethylsilyl) -β-D-ribofuranosyl]-3′-spiro-5″-(4″-amino-1, 2″-oxothiole 2″,2″-dioxide) (TSAO) analogues: synthesis and anti-HIV-1 activity. J. Med. Chem. 1994, 37, 4185-4198.
26. (b) Gunji, H.; Vasella, A. Oligonucleotides with a nucleobase-including backbone. Part 4. A convergent synthesis of ethylenediyl-linked adenosine tetramers Helv. Chim. Acta 2000, 83, 3229-3245.
27. (c) Epple, R.; Kudirka, R.; Greenberg, W. A. Solid-phase synthesis of nucleoside analogs. J. Comb. Chem. 2003, 5, 292-310.
28. (d) O'Mahony, G.; Ehrman, E.; Grøtli, M. Synthesis of adenosine-based fluorosides containing a novel heterocyclic ring system. Tetrahedron Lett. 2005, 46, 4745-6748.
29. (e) Moukha-Chafiq, O.; Taha, M. L.; Lazrek, H. B.; Pannecouque, C.; Witvrouw, M.; De Clercq, E.; Barascut, L.; Imbach, J. L. Synthesis and biological activity of 4-substituted 1-[1-(2-hydroxymethoxy)-methyl-1,2,3- triazol-(4 & 5)-ylmethyl]-1H-pyrazolo-[3,4-d]pyrimidines. Nucleosides, Nucleotides Nucleic Acids 2001, 20, 1797-1810.
30. (f) Moukha-Chafiq, O.; Taha, M. L.; Lazrek, H. B.; Vasseur, J. J.; Pannecouque, C.; Witvrouw, M.; De Clercq, E. Synthesis and biological evaluation of some 4-substituted 1-[1-(2-hydroxybutyl)-1,2,3-triazol-(4 & 5)-ylmethyl]-1H-pyrazolo[3,4-d]pyrimidines. Nucleosides, Nucleotides Nucleic Acids 2001, 20, 1811-1821.
31. (g) Wigerinck, P.; Van Aerschot, A.; Claes, P.; Balzani, J.; Declercq, E.; Herdewijn, P. 3′-(1,2,3-Triazol-1-yl)-2′,3′- dideoxythymidine and 3′-(1,2,3-triazol-1-yl)-2′,3′- dideoxyuridine. J. Heterocycl. Chem. 1989, 26, 1635-1642.
32. 2 receptor agonists with potent antihypertensive effects. J. Med. Chem. 1992, 35, 241-252.
33. Feldman, A. K.; Colasson, B.; Fokin, V. V. One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles from in situ generated azides. Org. Lett. 2004, 6, 3897-3899.
34. Temple, C., Jr.; Kussner, C. L.; Montgommery, J. A. Studies on the azidomethine-tetrazole equilibrium. V. 2- and 6-azidopurines. J. Org. Chem. 1966, 31, 2210-2215.
35. Lioux, T.; Gosselin, G.; Mathé, C. Azido/tetrazole tautomerism in 2-azidoadenine beta-D-pentofuranonucleoside derivatives. Eur. J. Org. Chem. 2003, 20, 3997-4002.
36. Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. Copper(I)-catalysed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates. J. Am. Chem. Soc. 2005, 127, 210-216.
37. 3 purinoceptor-like proteins J. Med. Chem. 2001, 44, 208-214.
38. Nordstedt, C.; Fredholm, B. B. A modification of a protein-binding method for rapid quantification of cAMP in cell-culture supernatants and body-fluid. Anal. Biochem. 1990, 189, 234.
39. 3 adenosine receptor. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 10365-10369.
40. Ohno, M.; Gao, Z. G.; Van Rompaey, P.; Tchilibon, S.; Kim, S. K.; Harris, B. A.; Blaustein, J.; Gross, A. S.; Duong, H. T.; Van Calenbergh, S.; Jacobson, K. A. Modulation of adenosine receptor affinity and intrinsic efficacy in nucleosides substituted at the 2-position. Biooorg. Med. Chem. 2004, 12, 2995-3007.
41. 3 receptor ligands. Bioorg. Med. Chem. 2006, 14, 1403-1412.
42. 3 adenosine receptors: Modification of the ribose moiety. Biochem. Pharmacol. 2004, 67, 893-901.
43. 6-(2-phenylethyl)adenosine derivatives as potent ligands. Bioorg. Med. Chem. 2004, 12, 2021-2034.
44. Palczewski, K.; Kumasaka, T.; Hori, T.; Behnke, C. A.; Motoshima, H.; Fox, B. A.; Le Trong, I.; Teller, D. C.; Okada, T.; Stenkamp, T. E.; Yamamoto, M.; Miyano, M. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 2000, 289, 739-745.
45. Bradford, M. M. Rapid and sensitive method for quantification of microgram quantities of protein utilizing principle of protein-dye binding. Anal. Biochem. 1976, 72, 248.
46. 3 adenosine receptor agonists. J. Med. Chem. 1998, 41, 3174-3185.
47. Halgren, T. A. MMFF VII. Characterization of MMFF94, MMFF94s, and other widely available force fields for conformational energies and for intermolecular-interaction energies and geometries. J. Comput. Chem. 1999, 20, 730-748.
48. Stewart, J. J. P. MOPAC: A semiempirical molecular orbital program. J. Comput.-Aided Mol. Des. 1990, 4, 1-105.
49. Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz, K. M., Jr.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids and organic molecules. J. Am. Chem. Soc. 1995, 117, 5179-5197.
50. 2 receptor ligands. J. Med. Chem. 1990, 33, 1919-1924.