9-{[3-fluoro-2-(hydroxymethyl)cyclopropylidene]methyl}adenines and -guanines. Synthesis and antiviral activity of all stereoisomers

Journal of Medicinal Chemistry

Volumn 49, Issue 20, 2006, Pages 6120-6128

  Zhou, Shaoman ^a   Kern, Earl R ^b   Gullen, Elizabeth ^c   Cheng, Yung Chi ^c   Drach, John C ^d   Tamiya, Sadahiro ^e,f   Mitsuya, Hiroaki ^e,f   Zemlicka, Jiri ^a  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF ALABAMA SCHOOL OF MEDICINE   (United States)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF MICHIGAN   (United States)

^e KUMAMOTO UNIV SCHOOL OF MEDICINE   (Japan)

^f NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

9 [[3 FLUORO 2 (HYDROXYMETHYL)CYCLOPROPYLIDENE]METHYL]ADENINE; 9 [[3 FLUORO 2 (HYDROXYMETHYL)CYCLOPROPYLIDENE]METHYL]GUANINE; ADENINE; ADENINE DERIVATIVE; ADENINE METHYLENE 3 FLUOROMETHYLENECYCLOPROPANE; ALDEHYDE DERIVATIVE; ALKENE DERIVATIVE; ANTIVIRUS AGENT; BENZYL DERIVATIVE; BROMINE; CARBENE; CARBOXYLIC ACID DERIVATIVE; CYCLOPROPANE DERIVATIVE; DIAZOACETIC ACID ETHYL ESTER; DRUG ANALOG; GUANINE DERIVATIVE; GUANINE METHYLENE 3 FLUOROMETHYLENECYCLOPROPANE; METHANOL DERIVATIVE; METHYL GROUP; NUCLEOSIDE DERIVATIVE; PURINE DERIVATIVE; SELENIUM; TRIBUTYLPHOSPHINE; TRICHLOROFLUOROMETHANE; UNCLASSIFIED DRUG;

ALKYLATION; ANTIVIRAL ACTIVITY; ARTICLE; BROMINATION; CHEMICAL REACTION; CIS TRANS ISOMERISM; CONTROLLED STUDY; DEBENZYLATION; DRUG HYDROLYSIS; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TRANSFORMATION; ENZYME SUBSTRATE; EPSTEIN BARR VIRUS; HUMAN CYTOMEGALOVIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; OXIDATION; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION; TRANS ISOMER; VARICELLA ZOSTER VIRUS;

ADENINE; ADENOSINE DEAMINASE; ANTIVIRAL AGENTS; CYCLOPROPANES; CYTOMEGALOVIRUS; CYTOPATHOGENIC EFFECT, VIRAL; GUANINE; HEPATITIS B VIRUS; HERPESVIRUS 1, HUMAN; HERPESVIRUS 2, HUMAN; HERPESVIRUS 3, HUMAN; HERPESVIRUS 4, HUMAN; HIV-1; HUMANS; PLAQUE ASSAY; PURINE NUCLEOSIDES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33749252341     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0607404     Document Type: Article

References (20)

1. Preliminary report: Zemlicka, J.; Zhou, S.; Kern, E. R.; Drach, J. C.; Mitsuya, H. Synthesis and Antiviral Activity of Methylene-3-fluorocyclopropane Analogues. 19th International Conference on Antiviral Research, San Juan, Puerto Rico, May 7-11. Antiviral Res. 2006, 70, A68.
2. Zemlicka, J. Unusual Analogues of Nucleosides: Chemistry and Biological Activity. In Recent Advances in Nucleosides: Chemistry and Chemotherapy; Chu, C. K., Ed.; Elsevier Science: Amsterdam, 2002; pp 327-357.
3. Zemlicka, J.; Chen, X. Methylenecyclopropane Analogues of Nucleosides as Antiviral Agents. In Frontiers in Nucleosides and Nucleic Acids; Schinazi, R. F., Liotta, D. C., Eds.; IHL Press: Tucker, Georgia, 2004; pp 267-307.
4. Zhou, S.; Breitenbach, J. M.; Borysko, K. Z.; Drach, J. C.; Kern, E. R.; Gullen, E.; Cheng, Y.-C.; Zemlicka, J. Synthesis and Antiviral Activity of (Z)- and (E)-2,2-[Bis(hydroxymethyl)cyclopropylidene]-methylpurines and -pyrimidines: Second-Generation Methylenecyclopropane Analogues of Nucleosides. J. Med. Chem. 2004, 47, 566-575.
5. Yan, Z.; Kern, E. R.; Gullen, E.; Cheng, Y.-C.; Drach, J. C.; Zemlicka, J. Nucleotides and Pronucleotides of 2,2-Bis(hydroxymethyl)cyclopropane Analogues of Purine Nucleosides: Synthesis and Antiviral Activity. J. Med. Chem. 2005, 48, 91-99.
6. Kern, E. R.; Kushner, N. L.; Hartline, C. B.; Williams-Azziz, S. L.; Harden, E. A.; Zhou, S.; Zemlicka, J.; Prichard, M. N. In Vitro Activity and Mechanism of Action of Methylenecyclopropane Analogues of Nucleosides against Herpes Virus Replication. Antimicrob. Agents Chemother. 2005, 49, 1039-1045.
7. Kern, E. R.; Bidanset, D. J.; Hartline, C. B.; Yan, Z.; Zemlicka, J.; Quenelle, D. C. Oral Activity of a Methylenecyclopropane Analogue, Cyclopropavir, in Animal Models for Cytomegalovirus Infections. Antimicrob. Agents Chemother. 2004, 48, 4745-4753.
8. Welch, J. T.; Eswarakrishnan, S. Fluorine in Bioorganic Chemistry: John Wiley & Sons: New York, 1991.
9. Pankiewicz, K. W. Fluorinated Nucleosides. Carbohydr. Res. 2000, 527, 87-105.
10. Wang, R.; Ksebati, M. B.; Corbett, T. H.; Kern, E. R.; Drach, J. C.; Zemlicka J. Methylene-gem-difluorocyclopropane Analogues of Nucleosides: Synthesis, Cyclopropene-Methylenecyclopropane Rearrangement, and Biological Activity. J. Med. Chem. 2001, 44, 4019-4022.
11. Zhou, S.; Kern, E. R.; Gullen, E.; Cheng, Y.-C.; Drach, J. C.; Matsumi, S.; Mitsuya, H.; Zemlicka, J. (Z)- and (E)-[2-Fluoro-2-(hydroxymethyl) cyclopropylidene]methylpurines and -pyrimidines, a New Class of Methylenecyclopropane Analogues of Nucleosides: Synthesis and Antiviral Activity. J. Med. Chem. 2004, 47, 6964-6972.
12. Cox, D. G.; Gurusamy, N.; Burton, D. J. Surprising Stereochemical Control of Wittig Olefination Involving Reaction of Fluorine-Containing Phosphoranium Salt and Aldehydes. J. Am. Chem. Soc. 1985, 107, 2811-2812.
13. Meyer, O. G. J.; Frohlich, R.; Haufe, G. Asymmetric Cyclopropanation of Vinyl Fluorides: Access to Enantiopure Monofluorinated Cyclopropane Carboxylates. Synthesis 2000, 1479-1490.
14. Wiley, G. A.; Hershkowitz, R. L.; Rein, B. M.; Chung, B. C. Studies in Organophosphorus Chemistry. I. Conversion of Alcohols and Phenols to Halides by Tertiary Phosphine Dihalides. J. Am. Chem. Soc. 1964, 86, 964-965.
15. Zhou, S.; Zemlicka, J. A New Alkylation-Elimination Method for Synthesis of Antiviral Fluoromethylenecyclopropane Analogues of Nucleosides. Tetrahedron 2005, 61, 7112-7116 and refs 20 and 21 cited therein.
16. Wang, R.; Harada, S.; Mitsuya, H.; Zemlicka, J. Inhibition of Human Immunodeficiency Virus Reverse Transcriptase by Synadenol Triphosphate and Its E-Isomer. J. Med. Chem. 2003, 46, 4799-4802.
17. Taber, D. F.; Walter, R.; Meagley, R. P. Intramolecular C-H Insertion by an Alkylidene Carbene: Diastereoselective Synthesis of a Taxol A Ring Synthon. J. Org. Chem. 1994, 59, 6014-6017.
18. Sharpless, B. K.; Young, M. W. Olefin Synthesis. Rate Enhancement of the Elimination of Alkyl Aryl Selenoxides by Electron-Withdrawing Substituents J. Org. Chem. 1975, 40, 947-949.
19. Smith, M. B.; March, J. March's Advanced Organic Chemistry, 5th edition; John Wiley & Sons: New York, 2001; pp 160-161.
20. 19F NMR indicated the presence of 5% of opposite stereoisomer.