Journal of Medicinal Chemistry
ARTICLE
analogues in the treatment of haematological malignancies. Expert Opin.
Pharmacother. 2001, 2, 929–943. (c) Parker, W. B.; Secrist, J. A., III;
Waud, W. R. Purine nucleoside antimetabolites in development for the
treatment of cancer. Curr. Opin. Invest. Drugs 2004, 5, 592–596.
(2) (a) Galmarini, C. M.; Mackey, J. R.; Dumontet, C. Nucleoside
analogues and nucleobases in cancer treatment. Lancet Oncol. 2002,
3, 415–242. (b) Galmarini, C. M.; Popowycz, F.; Joseph, B. Cytotoxic
nucleoside analogues: different strategies to improve their clinical
afficacy. Curr. Med. Chem. 2008, 15, 1072–1082.
(3) (a) Robins, R. K.; Revankar, G. R. Purine analogs and related
nucleosides and nucleotides as antitumor agents. Med. Res. Rev. 1985,
5, 273–296. (b) Plunkett, W.; Saunders, P. P. Metabolism and action of
purine nucleoside analogs. Pharmacol. Ther. 1991, 49, 239–268. (c)
Robak, T.; Korycka, A.; Kasznicki, M.; Wrzesien-Kus, A.; Smolewski, P.
Purine nucleoside analogues for the treatment of hematological malig-
nancies: pharmacology and clinical applications. Curr. Cancer Drug
Targets 2005, 5, 421–444. (d) Jordheim, L.; Galmarini, C. M.; Dumon-
tet, C. Drug resistance to cytotoxic nucleoside analogues. Curr. Drug
Targets 2003, 4, 443–460. (e) Jordheim, L. P.; Galmarini, C. M.;
Dumontet, C. Recent developments to improve the efficacy of cytotoxic
nucleoside analogues. Recent Patents Anti-Cancer Drug Discovery 2006,
1, 163–170. (f) Parker, W. B. Enzymology of Purine and Pyrimidine
Antimetabolites Used in the Treatment of Cancer. Chem. Rev. 2009,
109, 2880–2893.
(4) (a) Hocek, M.; Holꢁy, A.; Votruba, I.; Dvoꢀrꢁakovꢁa, H. Synthesis
and Cytostatic Activity of Substituted 6-Phenylpurine Bases and Nucleo-
sides: Application of the SuzukiꢀMiyaura Cross-Coupling Reactions of
6-Chloropurine Derivatives with Phenylboronic Acids. J. Med. Chem.
2000, 43, 1817–1825. (b) Hocek, M.; Holꢁy, A.; Votruba, I.; Dvoꢀrꢁakovꢁa,
H. Cytostatic 6-arylpurine nucleosides III. Synthesis and structureꢀ
activity relationship study in cytostatic activity of 6-aryl-, 6-hetaryl- and
6-benzylpurine ribonucleosides. Collect. Czech. Chem. Commun. 2001,
66, 483–499. (c) Hocek, M.; Nauꢀs, P.; Pohl, R.; Votruba, I.;
Furman, P. A.; Tharnish, P. M.; Otto, M. J. Cytostatic 6-arylpurine
Nucleosides 6. SAR in Anti-HCV and Cytostatic Activity of Extended
Series of 6-Hetarylpurine Ribonucleosides. J. Med. Chem. 2005, 48,
5869–5873.
(5) Nauꢀs, P.; Pohl, R.; Votruba, I.; Dꢀzubꢁak, P.; Hajdꢁuch, M.; Ameral,
R.; Birkus, G.; Wang, T.; Ray, A. S.; Mackman, R.; Cihlar, T.; Hocek, M.
6-(Het)aryl-7-Deazapurine Ribonucleosides as Novel Potent Cytostatic
Agents. J. Med. Chem. 2010, 53, 460–470.
(6) (a) Spꢁaꢀcilovꢁa, P.; Nauꢀs, P.; Pohl, R.; Votruba, I.; Snꢁaꢀsel, J.;
Zꢁabranskꢁa, H.; Pichovꢁa, I.; Ameral, R.; Birkuꢀs, G.; Cihlꢁaꢀr, T.; Hocek, M.
CycloSal-phosphate Pronucleotides of Cytostatic 6-(Het)aryl-7-deaza-
purine Ribonucleosides: Synthesis, Cytostatic Activity, and Inhibition of
Adenosine Kinases. ChemMedChem 2010, 5, 1386–1396. (b) Perlíkovꢁa,
P.; Pohl, R.; Votruba, I.; Shih, R.; Birkuꢀs, G.; Cihlꢁaꢀr, T.; Hocek, M.
Phosphoramidate pronucleotides of cytostatic 6-aryl-7-deazapurine
ribonucleosides. Bioorg. Med. Chem. 2011, 19, 229–242.
(7) (a) Anzai, K.; Nakamura, G.; Suzuki, S. A New Antibiotic,
Tubercidin. J. Antibiot. 1957, 10, 201–204. (b) Suzuki, S.; Marumo, S.
Chemical Structure of Tubercidin. J. Antibiot., Series A 1961, 13, 360–360. (c)
Acs, G.; Mori, M.; Reich, E. Biological + Biochemical Properties of Analogue
Antibiotic Tubercidin. Proc. Natl. Acad. Sci. U.S.A. 1964, 52, 493–501.
(8) (a) Ramasamy, K.; Imamura, N.; Robins, R. K.; Revankar, G. R. A
Facile Synthesis of Tubercidin And Related 7-Deazapurine Nucleosides
via The Stereospecific Sodium Salt Glycosylation Procedure. Tetrahe-
dron Lett. 1987, 28, 5107–5110. (b) Tolman, R. L.; Robins, R. K.;
Townsend, L. B. Pyrrolopyrimidine Nucleosides. III. The Total Synth-
esis of Toyocamycin, Sangivamycin, Tubercidin and Related Deriva-
tives. J. Am. Chem. Soc. 1969, 91, 2102–2108. (c) Bergstrom, D. E.;
Brattesani, A. J.; Ogawa, M. K.; Reddy, A. T.; Schweickert, M. J.;
Balzarini, J.; De Clercq, E. Antiviral Activity of C-5 Substituted Tuber-
cidin Analogues. J. Med. Chem. 1984, 27, 285–292. (d) Wu, R.;
Smidansky, E. D.; Oh, H. S.; Takhampunya, R.; Padmanabhan, R.;
Cameron, C. E.; Peterson, B. R. Synthesis of a 6-Methyl-7-deaza
Analogue of Adenosine That Potently Inhibits Replication of Polio
and Dengue Viruses. J. Med. Chem. 2010, 53, 7958–7966.
(9) (a) Cook, A. F.; Holman, M. J. Synthesis of the Natural Product
50-Deoxy-5-iodotubercidin and Related Halogenated Analogues. Nucleo-
sides Nucleotides 1984, 3, 401–411. (b) Ugarkar, B. G.; DaRe, J. M.;
Kopcho, J. J.; Browne, C. E., III; Schanzer, J. M.; Wiesner, J. B.; Erion,
M. D. Adenosine Kinase Inhibitors. 1. Synthesis, Enzyme Inhibition and
Antiseizure Activity of 5-Iodotubercidin Analogues. J. Med. Chem. 2000,
43, 2883–2893. (c) Ugarkar, B. G.; Castellino, A. J.; DaRe, J. S.; Ramirez-
Weinhouse, M.; Kopcho, J. J.; Rosengren, S.; Erion, M. D. Adenosine
Kinase Inhibitors. 3. Synthesis, SAR and Antiinflammatory Activity of a
SeriesofL-Lyxofuranosyl Nucleosides. J. Med. Chem. 2003, 46, 4750–4760.
(d) Kim, Y. A.; Sharon, A.; Chu, C. K.; Rais, R. H.; Al Safarjalani, O. N.;
Naguib, F. N. M.; el Kouni, M. H. StructureꢀActivity Relationships of
7-Deaza-6-benzylthioinosine Analogues as Ligands of Toxoplasma gondii
Adenosine Kinase. J. Med. Chem. 2008, 51, 3934–3945.
(10) (a) Eldrup, A. B.; Prhavc, M.; Brooks, J.; Bhat, B.; Prakash, T. P.;
Song, Q. L.; Bera, S.; Bhat, N.; Dande, P.; Cook, P. D.; Bennett, C. F.;
Carroll, S. S.; Ball, R. G.; Bosserman, M.; Burlein, C.; Colwell, L. F.; Fay,
J. F.; Flores, O. A.; Getty, K.; LaFemina, R. L.; Leone, J.; MacCoss, M.;
McMasters, D. R.; Tomassini, J. E.; Von Langen, D.; Wolanski, B.;
Olsen, D. B. Structureꢀactivity relationship of heterobase-modified 20-
C-methyl ribonucleosides as inhibitors of hepatitis C virus RNA
replication. J. Med. Chem. 2004, 47, 5284–5297. (b) Eldrup, A. B.;
Allerson, C. R.; Bennett, C. F.; Bera, S.; Bhat, B.; Bhat, N.; Bosserman,
M. R.; Brooks, J.; Burlein, C.; Carroll, S. S.; Cook, P. D.; Getty, K. L.;
MacCoss, M.; McMasters, D. R.; Olsen, D. B.; Prakash, T. P.; Prhavc, M.;
Song, Q. L.; Tomassini, J. E.; Xia, J. Structureꢀactivity relationship of
purine ribonucleosides for inhibition of hepatitis C virus RNA-depen-
dent RNA polymerase. J. Med. Chem. 2004, 47, 2283–2295. (c) Olsen,
D. B.; Eldrup, A. B.; Bartholomew, L.; Bhat, B.; Bosserman, M. R.;
Ceccacci, A.; Colwell, L. F.; Fay, J. F.; Flores, O. A.; Getty, K. L.; Grobler,
J. A.; LaFemina, R. L.; Markel, E. J.; Migliaccio, G.; Prhavc, M.; Stahlhut,
M. W.; Tomassini, J. E.; MacCoss, M.; Hazuda, D. J.; Carroll, S. S. A
7-deaza-adenosine analog is a potent and selective inhibitor of hepatitis
C virus replication with excellent pharmacokinetic properties. Antimi-
crob. Agents Chemother. 2004, 48, 3944–3953.
(11) (a) Ugarkar, B. G.; Castellino, A. J.; DaRe, J. M.; Kopcho, J. J.;
Wiesner, J. B.; Schanzer, J. M.; Erion, M. D. Adenosine Kinase Inhibitors.
2. Synthesis, Enzyme Inhibition and Antiseizure Activity of Diaryltu-
bercidin Analogues. J. Med. Chem. 2000, 43, 2894–2905. (b) Boyer,
S. H.; Ugarkar, B. G.; Solbach, J.; Kopcho, J.; Matelich, M. C.; Ollis, K.;
Gomez-Galeno, J. E.; Mendonca, R.; Tsuchiya, M.; Nagahisa, A.;
Nakane, M.; Wiesner, J. B.; Erion, M. D. Adenosine Kinase Inhibitors.
5. Synthesis, Enzyme Inhibition and Analgesic Activity of Erythro
Diarylturbercidin Analogs. J. Med. Chem. 2005, 48, 6430–6441. (c)
Bookser, B. C.; Matelich, M. C.; Ollis, K.; Ugarkar, B. G. Adenosine
Kinase Inhibitors. 4. 6,8-Disubstituted Purine Nucleoside Derivatives.
Synthesis, Conformation, and Enzyme Inhibition. J. Med. Chem. 2005,
48, 3389–3399.
(12) Seela, F.; Ming, X. 7-Functionalized 7-deazapurine β-D and β-L-
ribonucleosides related to tubercidin and 7-deazainosine: glycosylation
of pyrrolo[2,3-d]pyrimidines with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D or
β-L-ribofuranose. Tetrahedron 2007, 63, 9850–9861.
(13) (a) Western, E. C.; Daft, J. R.; Johnson, E. M.; Gannett, P. M.;
Shaughnessy, K. H. Efficient One-Step Suzuki Arylation of Unprotected
Halonucleosides, Using Water-Soluble Palladium Catalysts. J. Org. Chem.
ꢀ
2003, 68, 6767–6774. (b) Capek, P.; Pohl, R.; Hocek, M. Cross-Coupling
Reactions of Unprotected Halopurine Bases, Nucleosides, Nucleotides
and Nucleoside Triphosphates with 4-Boronophenylalanine in Water.
Synthesis of (Purin-8-yl)- and (Purin-6-yl)phenylalanines. Org. Biomol.
Chem. 2006, 4, 2278–2284.
(14) Park, S. B.; Dekeyser, M. A.; McDonald, P. T. Pesticidal
fluoroethyl pyrazoles. U.S. Patent US 2004/157892 A1, August 12, 2004.
(15) Jin, T.; Kamijo, S.; Yamamoto, Y. Copper-Catalyzed Synthesis
of N-Unsubstituted 1,2,3-Triazoles from Nonactivated Terminal Al-
kynes. Eur. J. Org. Chem. 2004, 3789–3791.
(16) (a) Jetter, M. C.; Reitz, A. B. Synthesis of 4-Substituted
Imidazoles via Palladium-Catalyzed Cross-Coupling Reactions. Synthesis
1998, 829–831. (b) Bell, A. S.; Roberts, D. A.; Ruddock, K. S. A synthesis
5506
dx.doi.org/10.1021/jm2005173 |J. Med. Chem. 2011, 54, 5498–5507