Synthesis of 2′,3′-dideoxynucleoside 5′-α-P-borano- β,γ-(difluoromethylene)triphosphates and their inhibition of HIV-1 reverse transcriptase

Journal of Medicinal Chemistry

Volumn 48, Issue 7, 2005, Pages 2695-2700

  Boyle, Nicholas A ^a   Rajwanshi, Vivek K ^a   Prhavc, Marija ^a   Wang, Guangyi ^a   Fagan, Patrick ^a   Chen, Fu ^a   Ewing, Gregory J ^a   Brooks, Jennifer L ^a   Hurd, Tiffany ^a   Leeds, Janet M ^a   Bruice, Thomas W ^a   Cook, P Dan ^a  

^a Biota Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2',3' DIDEOXYNUCLEOSIDE DERIVATIVE; 5' ALPHA PHOSPHOBORANO BETA,GAMMA (DIFLUOROMETHYLENE)TRIPHOSPHATE DERIVATIVE; ANTIVIRUS AGENT; BORANE DERIVATIVE; NUCLEOSIDE TRIPHOSPHATASE; PHOSPHITE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG; VIRUS DNA; ZIDOVUDINE DERIVATIVE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; BORON DERIVATIVE; DEOXYRIBONUCLEOTIDE; RNA DIRECTED DNA POLYMERASE;

ANIMAL CELL; ARTICLE; BORONATION; CHEMICAL REACTION KINETICS; CONTROLLED STUDY; DNA SYNTHESIS INHIBITION; DRUG POTENCY; DRUG STABILITY; DRUG SYNTHESIS; FETAL CALF SERUM; HUMAN IMMUNODEFICIENCY VIRUS 1; HYDROLYSIS; INHIBITION KINETICS; MOLECULAR MIMICRY; NONHUMAN; PROTEIN PHOSPHORYLATION; STRUCTURE ACTIVITY RELATION; VIRUS INHIBITION; ANIMAL; CATTLE; CHEMISTRY; IN VITRO STUDY; METABOLISM; STEREOISOMERISM; SYNTHESIS;

ANIMALS; ANTI-HIV AGENTS; BORON COMPOUNDS; CATTLE; DEOXYRIBONUCLEOTIDES; HIV-1 REVERSE TRANSCRIPTASE; REVERSE TRANSCRIPTASE INHIBITORS; STEREOISOMERISM;

EID: 20244364115     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm040101y     Document Type: Article

References (21)

1. Herdewijn, P.; Balzarini, J.; De Clercq, E. 2′,3′- Dideoxynucleoside Analogues as Antiviral Agents. In Advances in Antiviral Drug Design; De Clerck, E., Ed.; JAI Press: Greenwich, CT, 1993; Vol. 1.
2. St. Claire, M. H.; Richards, C. A.; Spector, T.; Weinhold, K. J.; Miller, W. H.; Langlois, A. J.; Furman, P. A. 3′-Azido-3′-deoxythymidine Triphosphate as an Inhibitor and Substrate of Purified Human Immunodeficiency Virus Reverse Transcriptase. Antimicrob. Agents Chemother. 1987, 31, 1972-1977.
3. Parker, W. B.; White, E. L.; Shaddix, S. C.; Ross, L. J.; Buckheit, R. W., Jr.; Germany, J. M.; Secrist, J. A., III; Vince, R.; Shannon, W. H. Mechanism of Inhibition of Human Immunodefficiency Virus Type 1 Reverse Transcriptase and Human DNA Polymerases α, β, γ by the 5′-Triphosphates of Carbovir, 3′-Azido-3′-deoxythymidine, 2′,3′-Dideoxyguanosine, and 3′-Dexoythymidine. J. Biol. Chem. 1991, 266, 1754-1762.
4. Jeffrey, J. L.; Feng, J. Y.; Qi, C. C. R.; Anderson, K. S.; Furman, P. A. Dioxolane Guanosine 5′-Triphosphate, an Alternative Substrate Inhibitor of Wild-Type and Mutant HIV-1 Reverse Transcriptase. J. Biol. Chem. 2003, 278, 18971-18979.
5. Wagner, C. R.; Iyer, V. V.; McIntee, E. J. Pronucleotides: Toward the In Vivo Delivery of Antiviral and Anticancer Nucleotides. Med. Res. Rev. 2000, 20, 417-451.
6. Farquhar, D.; Khan, S.; Srivastva, D. N.; Saunders, P. P. Synthesis and Antitumor Evaluation of Bis[(pivaloyloxy)methyl] 2′-deoxy-5-fluorouridine 5′-Monophosphate (FdUMP): A Strategy To Introduce Nucleotides into Cells. J. Med. Chem. 1994, 37, 3902-3909.
7. Lefebvre, I.; Perigaud, C.; Pompon, A.; Aubertin, A.-M.; Girardet, J.-L.; Kirn, A.; Gosselin, G.; Imbach, J.-L. Mononucleoside Phosphotriester Derivatives with S-Acyl-2-thioethyl Bioreversible Phosphate-Protecting Groups: Intracellular Delivery of 3′-Azido-2′,3′-dideoxythymidine 5′-Monophosphate. J. Med. Chem. 1995, 38, 3941-3950.
8. Siddiqui, A. Q.; McGuigan, C.; Ballatore, C.; Zuccotto, F.; Gilbert, I. H.; De Clercq, E.; Balzarini, J. Design and Synthesis of Lipophilic Phosphoramidate d4T-MP Prodrugs Expressing High Potency against HIV in Cell Culture: Structure Determinants for in Vitro Activity and QSAR. J. Med. Chem. 1999, 42, 4122-4128.
9. Meier, C.; Knispel, T.; De Clercq, E.; Balzarini, J. CycloSal- Pronucleotides of 2′,3′-Dideoxyadenosin and 2′,3′- Dideoxy-2′,3′-didehydroadenosine: Synthesis and Antiviral Evaluation of a Highly Efficient Nucleotide Delivery System. J. Med. Chem. 1999, 42, 1604-1614.
10. De Clercq, E. Antiviral Drugs: Current State of the Art. J. Clin. Virol. 2001, 22, 73-89.
11. Bayes, M.; Rabasseda, X.; Prous, J. R. Gateways to Clinical Trials. Methods Find. Exp. Clin. Pharmacol. 2003, 25, 53-76.
12. Wang, G.; Boyle, N.; Chen, F.; Rajappan, V.; Fagan, P.; Brooks, J. L.; Hurd, T.; Leeds, J. M.; Rajwanshi, V. K.; Jin, Y.; Prhavc, M.; Bruice, T. W.; Cook, P. D. J. Med. Chem. 2004, 47, 6902-6913.
13. He, K.; Hasan, A.; Krzyzanowska, B.; Shaw, B. R. Synthesis and Separation of Ribonucleoside 5′-(α-P-Borano)triphosphates. J. Org. Chem. 1998, 63, 5769-5773.
14. 7-Cyanoborane-2′-deoxyguanosine 5′-Triphosphate Is a Good Substrate for DNA Polymerase. Biochemistry 1995, 34, 11963-11969.
15. Tomasz, J.; Shaw, B. R.; Porter, K.; Spielvogel, B. F.; Sood, A.; 5′-P-Borane-Substituted Thymidine Monophosphate and Triphosphate. Angew. Chem., Int. Ed. Engl. 1992, 31, 1373-1375.
16. 1 Receptor Agonists. J. Med. Chem. 2002, 45, 5384-5396.
17. Meyer, P.; Scheider, B.; Sarfati, S.; Deville-Bonne, D.; Guerreiro, C.; Boretto, J.; Janin, J.; Veron, M.; Canard, B. Structural Basis for Activation of α-Boranophosphate Nucleotide Analogues Targeting Drug-Resistant Reverse Transcriptase. EMBO J. 2000, 19, 3520-3529.
18. Arzumanov, A. A.; Semizarov, D. G.; Victorova, L. S.; Dyatkina, N. B.; Krayevsky, A. A. J. Biol. Chem. 1996, 271, 24389-24394.
19. Hao, Z.; Cooney, D. A.; Farquhar, D.; Ferno, C. F.; Zhang, K.; Masood, R.; Wilson, Y.; Hartman, N. R.; Balzarini, J.; Johns, D. G. Potent DNA Chain Termination Activity and Selective Inhibition of Human Immunodeficiency Virus Reverse Transcriptase by 2′,3′-Dideoxyuridine-5′-triphosphate. Mol. Pharmacol. 1989, 37, 157-163.
20. 1-Receptor. 1. A Synthetic, Biochemical, and NMR Approach. J. Med. Chem. 1999, 42, 5325-5337.
21. Li, P.; Dobrikov, M.; Liu, H.; Shaw, B. R. Synthesis of Acyclothymidine Triphosphate and α-P-Boranotriphosphate and Their Substrate Properties with Retroviral Reverse Transcriptase. Org. Lett. 2003, 5, 2401-2403.