5-(1-Acetoxyvinyl)-cyclosaligenyl-2′,3′-dideoxy-2′, 3′- didehydrothymidine monophosphates, a second type of new, enzymatically activated cyclosaligenyl pronucleotides

Journal of Medicinal Chemistry

Volumn 51, Issue 24, 2008, Pages 8115-8123

  Gisch, Nicolas ^a   Pertenbreiter, Florian ^a   Balzarini, Jan ^b   Meier, Chris ^a  

^a UNIVERSITY OF HAMBURG   (Germany)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

5 (1 ACETOXYVINYL) 3 TERT BUTYL CYCLOSALIGENYL 2',3' DIDEHYDROTHYMIDINE MONOPHOSPHATE; 5 (1 ACETOXYVINYL) CYCLOSALIGENYL 2',3' DIDEOXY 2',3' DIDEHYDROTHYMIDINE MONOPHOSPHATE; CYCLOSALIGENYL PHOSPHATE TRIESTER DERIVATIVE; CYCLOSALIGENYL PRONUCLEOTIDE DERIVATIVE; NUCLEOSIDE TRANSPORTER; THYMIDINE KINASE; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CHEMICAL REACTION KINETICS; CIRCULAR DICHROISM; CONCEPT FORMATION; DIASTEREOISOMER; DRUG DELIVERY SYSTEM; ELECTRON TRANSPORT; ENZYME ACTIVATION; ENZYME MECHANISM; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 2; HYDROLYSIS; ISOMERIZATION; NUCLEOSIDE TRANSPORT;

ANTI-HIV AGENTS; CHEMISTRY, PHARMACEUTICAL; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CIRCULAR DICHROISM; DIDEOXYNUCLEOTIDES; DRUG DESIGN; ELECTRONS; HIV-1; HIV-2; HUMANS; HYDROGEN-ION CONCENTRATION; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, CHEMICAL; NUCLEOTIDES; STAVUDINE; THYMINE NUCLEOTIDES;

EID: 58149097702     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm801197f     Document Type: Article

References (16)

1. Meier, C. cycloSal Phosphates as Chemical Trojan Horses for Intracellular Nucleotide and Glycosylmonophosphate Delivery. Chemistry Meets Biology. Eur. J. Org. Chem. 2006, 1081-1102.
2. Meier, C. cycloSal-Pronucleotides. Design of Chemical Trojan Horses. Mini-Rev. Med. Chem. 2002, 2, 219-234.
3. Meier, C.; Ruppel, M. F. H.; Vukadinović, D.; Balzarini, J. Second generation of cycloSal-Pronucleotides with Esterase-Cleavable Sites: The "Lock-In"-Concept. Nucleosides, Nucleotides Nucleic Acids 2004, 23, 89-115.
4. Meier, C.; Ducho, C.; Jessen, H.; Vukadinović-Tenter, D.; Balzarini, J. Second-Generation cycloSal-d4TMP Pronucleotides Bearing Esterase-Cleavable Sites. The "Trapping" Concept. Eur. J. Org. Chem. 2006, 197-206.
5. Jessen, H. J.; Balzarini, J.; Meier, C. Intracellular Trapping of cycloSal-Pronucleotides: Modification of Prodrugs with Amino Acid Esters. J. Med. Chem. 2008, 51, 6592-6598.
6. Gisch, N.; Balzarini, J.; Meier, C. Enzymatically Activated cycloSal-d4T-monophosphates: The Third Generation of cycloSal- Pronucleotides. J. Med. Chem. 2007, 50, 1658-1667.
7. Gisch, N.; Balzarini, J.; Meier, C. Studies on Enzyme-Cleavable Dialkoxymethyl-cyclosaligenyl-2′,3′-dideoxy-2′, 3′-didehydrothymidine Monophosphates. J. Med. Chem. 2008, 51, 6752-6760.
8. U.S. Patent Appl. 2006058370, 2006.
9. Yanagi, T.; Kikuchi, K.; Takeuchi, H.; Ishikawa, T.; Nishimura, T.; Yamamoto, I. The Practical Synthesis of a Uterine Relaxant, Bis(2-{[(2S)- 2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxy-ethyl)-phenyl]ethyl}amino) -1,2,3,4-tetrahydronaphthalen-7-yl]oxy}-N,N-dimethylacetamide) Sulfate (KUR-1246). Chem. Pharm. Bull. 2001, 49, 1018-1023.
10. Buchanan, D. J.; Dixon, D. J.; Looker, B. E. A Short Stereoselective Synthesis of (R)-Salmeterol. Synlett 2005, 12, 1948-1950.
11. Eames, J.; Coumbarides, G. S.; Suggate, M. J.; Weerasooriya, N. Investigations into the Regioselective C-Deuteration of Acyclic and Exocyclic Enolates. Eur. J. Org. Chem. 2003, 634-641.
12. 4 was used and the yield for this step could be increased to 95%. So compound 15 can be prepared from 2-tert-butylphenol in 54% yield over three steps.
13. Kita, Y.; Takeda, Y.; Iio, K.; Yokogawa, K.; Takahashi, K.; Akai, S. An Efficient Preparation of peri-Hydroxy Dihydroquinone Derivatives through a Pummerer-Type Rearrangement of Silylene-Protected peri-Hydroxy Aromatic Sulfoxides. Tetrahedron Lett. 1996, 37, 7545-7548.
14. Long, Y.; Jiang, X.; Dayam, R.; Sanchez, T.; Shoemaker, R.; Sei, S.; Neamati, N. Rational Design and Synthesis of Novel Dimeric Diketoacid-Containing Inhibitors of HIV-1 Integrase: Implication for Binding to Two Metal Ions on the Active Site of Integrase. J. Med. Chem. 2004, 47, 2561-2573.
15. Pearson, A. J.; Zhang, P.; Lee, K. Application of Arene-Ruthenium Chemistry to a Formal Total Synthesis of OF 4949 III. J. Org. Chem. 1996, 61, 6581-6586.
16. Ducho, C.; Balzarini, J.; Naesens, L.; De Clercq, E.; Meier, C. Aryl-Substituted and Benzo-Annulated cycloSal-Derivatives of 2′,3′-Dideoxy-2′,3′-didehydrothymidine Monophosphate. Correlation of Structure, Hydrolysis Properties and Anti-HIV Activity. Antiviral Chem. Chemother. 2002, 13, 129-141.