C McGuigan

Summary

Affiliation: Cardiff University
Country: UK

Publications

  1. ncbi request reprint Bicyclic nucleoside inhibitors of varicella-zoster virus: synthesis and biological evaluation of 2',3'-dideoxy-3'-fluoro and 2'-deoxy-xylo derivatives
    A Carangio
    Welsh School of Pharmacy, University of Wales Cardiff, Cardiff, UK
    Nucleosides Nucleotides Nucleic Acids 22:935-7. 2003
  2. ncbi request reprint Application of phosphoramidate pronucleotide technology to abacavir leads to a significant enhancement of antiviral potency
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, U K
    J Med Chem 48:3504-15. 2005
  3. doi request reprint Design, synthesis and biological evaluation of phosphorodiamidate prodrugs of antiviral and anticancer nucleosides
    Christopher McGuigan
    School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK Electronic address
    Eur J Med Chem 70:326-40. 2013
  4. doi request reprint Phosphorodiamidates as a promising new phosphate prodrug motif for antiviral drug discovery: application to anti-HCV agents
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK
    J Med Chem 54:8632-45. 2011
  5. ncbi request reprint Preclinical development of bicyclic nucleoside analogues as potent and selective inhibitors of varicella zoster virus
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    J Antimicrob Chemother 60:1316-30. 2007
  6. ncbi request reprint Application of phosphoramidate ProTide technology significantly improves antiviral potency of carbocyclic adenosine derivatives
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    J Med Chem 49:7215-26. 2006
  7. ncbi request reprint Aryl furano pyrimidines: the most potent and selective anti-VZV agents reported to date
    Christopher McGuigan
    Welsh School of Pharmacy, University of Wales Cardiff, Redwood Building, King Edward Vll Avenue, Cardiff CF1 3XF, UK
    Antiviral Res 71:149-53. 2006
  8. ncbi request reprint Anti-cancer ProTides: tuning the activity of BVDU phosphoramidates related to thymectacin
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    Bioorg Med Chem 13:3219-27. 2005
  9. ncbi request reprint Synthesis and antiviral evaluation of some 3'-fluoro bicyclic nucleoside analogues
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Nucleosides Nucleotides Nucleic Acids 23:1-5. 2004
  10. ncbi request reprint Discovery of a new family of inhibitors of human cytomegalovirus (HCMV) based upon lipophilic alkyl furano pyrimidine dideoxy nucleosides: action via a novel non-nucleosidic mechanism
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    J Med Chem 47:1847-51. 2004

Collaborators

Detail Information

Publications77

  1. ncbi request reprint Bicyclic nucleoside inhibitors of varicella-zoster virus: synthesis and biological evaluation of 2',3'-dideoxy-3'-fluoro and 2'-deoxy-xylo derivatives
    A Carangio
    Welsh School of Pharmacy, University of Wales Cardiff, Cardiff, UK
    Nucleosides Nucleotides Nucleic Acids 22:935-7. 2003
  2. ncbi request reprint Application of phosphoramidate pronucleotide technology to abacavir leads to a significant enhancement of antiviral potency
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, U K
    J Med Chem 48:3504-15. 2005
    ..In addition, the pharmacokinetic disposition of the abacavir phenylethoxyalaninyl phosphoramidate was evaluated in Cynomolgus monkeys...
  3. doi request reprint Design, synthesis and biological evaluation of phosphorodiamidate prodrugs of antiviral and anticancer nucleosides
    Christopher McGuigan
    School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK Electronic address
    Eur J Med Chem 70:326-40. 2013
    ..This work further validates the phosphorodiamidate approach as a monophosphate prodrug motif with broad application in the antiviral and anticancer fields. ..
  4. doi request reprint Phosphorodiamidates as a promising new phosphate prodrug motif for antiviral drug discovery: application to anti-HCV agents
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK
    J Med Chem 54:8632-45. 2011
    ..This phosphorodiamidate prodrug method may have broad application outside of HCV and antivirals as it offers many of the advantages of phosphoramidate ProTides but without the chirality issues present in most cases...
  5. ncbi request reprint Preclinical development of bicyclic nucleoside analogues as potent and selective inhibitors of varicella zoster virus
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    J Antimicrob Chemother 60:1316-30. 2007
    ..To progress the anti-varicella-zoster-virus (VZV) aryl bicyclic nucleoside analogues (BCNAs) to the point of Phase 1 clinical trial for herpes zoster...
  6. ncbi request reprint Application of phosphoramidate ProTide technology significantly improves antiviral potency of carbocyclic adenosine derivatives
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    J Med Chem 49:7215-26. 2006
    ..With a view to preclinical candidate selection we carried out metabolic stability studies using cynomolgus monkey liver and intestinal S9 fractions...
  7. ncbi request reprint Aryl furano pyrimidines: the most potent and selective anti-VZV agents reported to date
    Christopher McGuigan
    Welsh School of Pharmacy, University of Wales Cardiff, Redwood Building, King Edward Vll Avenue, Cardiff CF1 3XF, UK
    Antiviral Res 71:149-53. 2006
    ..Some structural modification, such as aryl substitution, is tolerated, while little sugar modification is acceptable. We herein summarise their biological profiles and structure activity relationships as discovered to date...
  8. ncbi request reprint Anti-cancer ProTides: tuning the activity of BVDU phosphoramidates related to thymectacin
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    Bioorg Med Chem 13:3219-27. 2005
    ..This derivative emerges as a low micromolar inhibitor of HT115 cells and a new lead for further optimisation...
  9. ncbi request reprint Synthesis and antiviral evaluation of some 3'-fluoro bicyclic nucleoside analogues
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Nucleosides Nucleotides Nucleic Acids 23:1-5. 2004
    ..The compounds are tested against a range of herpes viruses and display poor activity, strongly supporting the notion of the importance of the presence of a 3'-OH for antiviral activity...
  10. ncbi request reprint Discovery of a new family of inhibitors of human cytomegalovirus (HCMV) based upon lipophilic alkyl furano pyrimidine dideoxy nucleosides: action via a novel non-nucleosidic mechanism
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    J Med Chem 47:1847-51. 2004
    ..They represent new leads in the discovery of improved therapies for HCMV, particularly in view of their novel mechanism of action...
  11. ncbi request reprint Novel bicyclic furanopyrimidines with dual anti-VZV and -HCMV activity
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    Bioorg Med Chem Lett 13:4511-3. 2003
    ..Uniquely amongst compounds of this family to date the present agents show dual anti- (VZV) and human cytomegalovirus (HCMV) activity. The lead compounds inhibit VZV at 10 nM and HCMV at 5 microM...
  12. doi request reprint Successful kinase bypass with new acyclovir phosphoramidate prodrugs
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, UK
    Bioorg Med Chem Lett 18:4364-7. 2008
    ..Unlike the parent nucleoside these novel phosphate prodrugs retain antiviral potency versus the ACV-resistant virus strain, suggesting an efficient bypass of the viral thymidine kinase...
  13. doi request reprint Phosphate prodrugs derived from N-acetylglucosamine have enhanced chondroprotective activity in explant cultures and represent a new lead in antiosteoarthritis drug discovery
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    J Med Chem 51:5807-12. 2008
    ..By comparison to the N-acetyl glucosamine parent, some of the analogues show a significant enhancement in efficacy in the inhibition of inflammatory cytokine-induced proteoglycan degradation...
  14. doi request reprint Phosphoramidate ProTides of the anticancer agent FUDR successfully deliver the preformed bioactive monophosphate in cells and confer advantage over the parent nucleoside
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK
    J Med Chem 54:7247-58. 2011
    ..We also find that the ProTides retain activity in mycoplasma infected cells, unlike FUDR. Data suggest these compounds to be worthy of further progression...
  15. doi request reprint Phosphoramidate ProTides of 2'-C-methylguanosine as highly potent inhibitors of hepatitis C virus. Study of their in vitro and in vivo properties
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, U K
    J Med Chem 53:4949-57. 2010
    ..This represents one of the most thorough cross-species studies of ProTides to date...
  16. doi request reprint Aryloxy phosphoramidate triesters: a technology for delivering monophosphorylated nucleosides and sugars into cells
    Youcef Mehellou
    Cardiff University, UK
    ChemMedChem 4:1779-91. 2009
    ..The development of the phosphoramidate technology, mechanism of action and the application of the technology to various monophosphorylated nucleosides and sugars will be reviewed...
  17. doi request reprint FV100 as a new approach for the possible treatment of varicella-zoster virus infection
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK
    J Antimicrob Chemother 64:671-3. 2009
    ..It is exquisitely potent and selective for human VZV. FV100 has recently entered a randomized, controlled Phase II clinical trial for the treatment of shingles, sponsored by Inhibitex...
  18. doi request reprint The phosphoramidate ProTide approach greatly enhances the activity of beta-2'-C-methylguanosine against hepatitis C virus
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK
    Bioorg Med Chem Lett 19:4316-20. 2009
    ..The carboxypeptidase mediated hydrolysis of several ProTides showed a predictive correlation with their activity versus HCV in replicon...
  19. doi request reprint The application of phosphoramidate ProTide technology to the potent anti-HCV compound 4'-azidocytidine (R1479)
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, UK
    Bioorg Med Chem Lett 19:4250-4. 2009
    ..Sub-muM inhibitors of HCV emerge. The compounds are all non-cytotoxic in the replicon assay. We herein report detailed SARs for each of the regions of the ProTide...
  20. doi request reprint The application of the phosphoramidate ProTide approach confers micromolar potency against hepatitis C virus on inactive agent 4'-azidoinosine: kinase bypass on a dual base/sugar modified nucleoside
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Bioorg Med Chem Lett 19:3122-4. 2009
    ..This is a rare example of an inosine nucleoside analogue with potent antiviral activity and further supports the notion of ProTides as a drug discovery motif...
  21. doi request reprint Alkenyl substituted bicyclic nucleoside analogues retain nanomolar potency against Varicella Zoster Virus
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, UK
    Bioorg Med Chem 17:3025-7. 2009
    ..The para-substituted analogues retain the nanomolar potency we have reported for p-alkyl analogues, while the ortho- and meta-alkenyl systems lose 3-4 orders of potency...
  22. ncbi request reprint Halophenyl furanopyrimidines as potent and selective anti-VZV agents
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Antivir Chem Chemother 14:165-70. 2003
    ..The p-fluorophenyl compound is unique amongst compounds of this class in being inactive as an antiviral. The possible origins of these marked SARs are discussed...
  23. ncbi request reprint Anti-varicella-zoster virus bicyclic nucleosides: replacement of furo by pyrro base reduces antiviral potency
    C McGuigan
    Welsh School of Pharmacy, Cardiff University, UK
    Antivir Chem Chemother 11:343-8. 2000
    ..We herein report the synthesis, characterization and antiviral evaluation of these novel compounds...
  24. ncbi request reprint Alkyloxyphenyl furano pyrimidines as potent and selective anti-VZV agents with enhanced water solubility
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, UK
    Antivir Chem Chemother 13:91-9. 2002
    ..We report the synthesis, characterisation and antiviral evaluation of this series and note the retention of extremely high antiviral potency, with EC50 values as low as 1 nanomolar...
  25. ncbi request reprint Phosphoramidate derivatives of stavudine as inhibitors of HIV: unnatural amino acids may substitute for alanine
    C McGuigan
    Welsh School of Pharmacy, Cardiff University, UK
    Antivir Chem Chemother 11:111-6. 2000
    ..These data are further probed by the application of our recently reported 31P-NMR-based carboxyl esterase assay, with informative results...
  26. ncbi request reprint Synthesis and antiviral activity of acyclovir-5'-(phenyl methoxy alaninyl) phosphate as a possible membrane-soluble nucleotide prodrug
    C McGuigan
    Welsh School of Pharmacy, Cardiff University, UK
    Bioorg Med Chem Lett 10:645-7. 2000
    ..However, the biological activities of this derivative against a range of viruses indicated poor intracellular phosphate delivery, in marked contrast to the earlier successful delivery of several dideoxy anti-HIV nucleotides...
  27. ncbi request reprint Potent and selective inhibition of varicella-zoster virus (VZV) by nucleoside analogues with an unusual bicyclic base
    C McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, CF1 3XF, U K
    J Med Chem 42:4479-84. 1999
    ..The novel structure of these compounds, coupled with their ease of synthesis, excellent antiviral profile, and promising physical properties, makes them of great interest for possible antiviral drug development...
  28. ncbi request reprint Furano pyrimidines as novel potent and selective anti-VZV agents
    C McGuigan
    Welsh School of Pharmacy, University of Wales Cardiff, UK
    Antivir Chem Chemother 12:77-89. 2001
    ..Here, we review the discovery, synthesis, characterization, antiviral profile, SAR, mechanism of action and development prospects for this new family of antivirals...
  29. ncbi request reprint Highly potent and selective inhibition of varicella-zoster virus by bicyclic furopyrimidine nucleosides bearing an aryl side chain
    C McGuigan
    Welsh School of Pharmacy and Department of Optometry and Vision Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, U K
    J Med Chem 43:4993-7. 2000
    ....
  30. ncbi request reprint Synthesis and anti-HIV activity of some novel chain-extended phosphoramidate derivatives of d4T (stavudine): esterase hydrolysis as a rapid predictive test for antiviral potency
    C McGuigan
    Welsh School of Pharmacy, University of Wales Cardiff, UK
    Antivir Chem Chemother 9:109-15. 1998
    ..The reasons for the virtual lack of anti-HIV activity appear to involve poor enzyme-mediated hydrolysis...
  31. ncbi request reprint Lactate cannot substitute for alanine in d4T-based anti-HIV nucleotide prodrugs--despite efficient esterase-mediated hydrolysis
    C McGuigan
    Welsh School of Pharmacy, Cardiff University, UK
    Bioorg Med Chem Lett 8:2949-54. 1998
    ..Here we report that lactate analogues, with a simple change of bridging nitrogen for oxygen, are virtually inactive as antiviral agents and apparently do not achieve intracellular nucleoside phosphate delivery...
  32. ncbi request reprint Synthesis, anti-human immunodeficiency virus activity and esterase lability of some novel carboxylic ester-modified phosphoramidate derivatives of stavudine (d4T)
    C McGuigan
    Welsh School of Pharmacy, Cardiff University, UK
    Antivir Chem Chemother 9:473-9. 1998
    ..However, no clear positive correlation emerged, indicating that, at least within this series, factors other than simple esterase lability may be the major determinants of antiviral potency...
  33. ncbi request reprint The journey towards elucidating the anti-HCMV activity of alkylated bicyclic furano pyrimidines
    M R Kelleher
    Welsh School of Pharmacy, Cardiff University, Redwood Building, Edward VI Ave, CF10 3XF, Cardiff, UK
    Nucleosides Nucleotides Nucleic Acids 24:643-5. 2005
    ..O-alkylated derivatives were almost invariably found to be at least equiactive with their N-alkylated counterparts. At this point, little change in activity has been found with large variation in N- and O-substituent...
  34. ncbi request reprint Synthesis and antiviral evaluation of phosphoramidate derivatives of (E)-5-(2-bromovinyl)-2'-deoxyuridine
    S A Harris
    Welsh School of Pharmacy, Cardiff University, UK
    Antivir Chem Chemother 12:293-300. 2001
    ..It appears that successful kinase bypass by phosphoramidates is highly dependent on the nucleoside analogue, amino acid and ester structure, as well as the cell line to which the drugs are exposed...
  35. ncbi request reprint Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity
    A Brancale
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, CF10 3XF, Cardiff, UK
    Bioorg Med Chem Lett 11:2507-10. 2001
    ..Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family are herein reported. The compounds retain full antiviral potency in comparison to the furo parent...
  36. ncbi request reprint Bicyclic nucleoside inhibitors of varicella-zoster virus (VZV): Pd-catalysed synthesis of 5-aryl derivatives and their biological evaluation
    A Carangio
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Antivir Chem Chemother 12:187-97. 2001
    ..Possible reasons for this structure activity relationship are discussed...
  37. ncbi request reprint Bicyclic nucleoside inhibitors of Varicella-Zoster Virus (VZV): the effect of terminal unsaturation in the side chain
    S Srinivasan
    Welsh School of Pharmacy, Cardiff University, King Edward, Cardiff, UK
    Bioorg Med Chem Lett 11:391-3. 2001
    ..In particular, analogues with terminal unsaturation in the side chain are reported. Whilst terminal alkenyl derivatives are potent antivirals, the corresponding terminal alkynyls are poorly active...
  38. ncbi request reprint Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA
    C Ballatore
    Welsh School of Pharmacy, Cardiff University, UK
    Bioorg Med Chem Lett 11:1053-6. 2001
    ..In vitro enzymatic studies and structure-activity relationships indicate that the degradation mechanism of such prodrugs may be the same as that described for the phosphoramidate triesters of nucleotide analogues...
  39. ncbi request reprint Bicyclic nucleoside inhibitors of varicella-zoster virus: 5'-chloro and 3'-chloro derivatives
    G Luoni
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Nucleosides Nucleotides Nucleic Acids 22:931-3. 2003
    ..The compounds have been tested against VZV and CMV, but displayed no significant in vitro activity...
  40. ncbi request reprint Synthesis and biological evaluation of N- and O-alkylated bicyclic furanopyrimidines as non-nucleosidic inhibitors of human cytomegalovirus
    M R Kelleher
    Welsh School of Pharmacy, Redwood Building, King Edward VII Ave, CF10 3XF, Cardiff, UK
    Nucleosides Nucleotides Nucleic Acids 24:639-41. 2005
    ..These compounds were tested against HCMV strains, and the first case of submicromolar activity was observed...
  41. doi request reprint 2'-Fluorosugar analogues of the highly potent anti-varicella-zoster virus bicyclic nucleoside analogue (BCNA) Cf 1743
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF103XF, UK
    Bioorg Med Chem Lett 19:6264-7. 2009
    ..In contrast, the alpha-fluoro- and 2',2'-difluoro BCNA derivatives were markedly less (approximately 100-fold) antivirally active...
  42. ncbi request reprint Bicyclic nucleoside inhibitors of varicella-zoster virus (VZV): effect of terminal unsaturation in the side-chain
    S Srinivasan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Ave, Cardiff CF10 3XF, United Kingdom
    Nucleosides Nucleotides Nucleic Acids 20:763-6. 2001
    ..In particular, we report the synthesis of analogues with terminal unsaturation in the side-chain. Terminal alkenyl derivatives were found to be potent antivirals whereas the terminal alkynyls displayed poor activity...
  43. ncbi request reprint Bicyclic furo pyrimidine nucleosides with aryloxyphenyl and halophenyl substituted side chains as potent and selective varicella-zoster virus inhibitors
    S Blewett
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3XF, United Kingdom
    Nucleosides Nucleotides Nucleic Acids 20:1063-6. 2001
    ..A series of alkoxyphenyl compounds (5a-5g) and two halophenyl derivatives (5h and 5i) were successfully synthesised and displayed anti-VZV activity at low microM concentrations...
  44. ncbi request reprint Synthesis and in vitro evaluation of novel anti-varicella-zoster virus (VZV) nucleosides
    A Carangio
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3XF, United Kingdom
    Nucleosides Nucleotides Nucleic Acids 20:653-6. 2001
    ..Synthesised compounds (4a-i) showed an anti-VZV activity at low microM concentration, comparable to that of current treatment acyclovir...
  45. ncbi request reprint Synthesis of unusual bicyclic nucleosides bearing an unsaturated side-chain, as potential inhibitors of varicella-zoster virus (VZV)
    O Bidet
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Nucleosides Nucleotides Nucleic Acids 22:817-9. 2003
  46. ncbi request reprint Topical delivery of retinyl ascorbate co-drug. 5. In vitro degradation studies
    K Abdulmajed
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Skin Pharmacol Physiol 19:248-58. 2006
    ..5 cm(2) of skin (average diffusion area in the Franz cells used in our skin penetration studies) was 0.06 mg cm(-2) and 0.01 mg cm(-2) for fresh and stored extracts, respectively...
  47. ncbi request reprint Bicyclic nucleoside inhibitors of varicella-zoster virus: effect of terminal aryl substitution in the side-chain
    A Carangio
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, UK
    Antivir Chem Chemother 13:263-71. 2002
    ..A possible correlation between antiviral activity and conformational freedom of the side-chain is discussed...
  48. ncbi request reprint Synthesis and antiviral activity of the carbocyclic analogue of the highly potent and selective anti-VZV bicyclo furano pyrimidines
    Marco D Migliore
    Welsh School of Pharmacy, Cardiff University, UK
    J Med Chem 50:6485-92. 2007
    ..However, other factors besides affinity for VZV-TK must account for the greatly reduced antiviral potency...
  49. ncbi request reprint Design, synthesis, and anti-HIV activity of 2',3'-didehydro-2',3'-dideoxyuridine (d4U), 2',3'-dideoxyuridine (ddU) phosphoramidate 'ProTide' derivatives
    Youcef Mehellou
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, UK
    Bioorg Med Chem Lett 17:3666-9. 2007
    ..The findings from the modeling studies provide compelling evidence for the lack of anti-HIV activity of d4U phosphoramidates, in contrast with the corresponding ddU phosphoramidates...
  50. ncbi request reprint Bicyclic nucleoside inhibitors of varicella-zoster virus modified on the sugar moiety: 3' and 5' derivatives
    Giovanna M Luoni
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Antivir Chem Chemother 15:333-41. 2004
    ..These results confirm free 5'-OH and 3'-OH as necessary requirements for efficient recognition by VZV TK and for potent anti-VZV activity in cell culture...
  51. ncbi request reprint First example of phosphoramidate approach applied to a 4'-substituted purine nucleoside (4'-azidoadenosine): conversion of an inactive nucleoside to a submicromolar compound versus hepatitis C virus
    Plinio Perrone
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    J Med Chem 50:5463-70. 2007
    ..The benzyl ester and the l-naphthyl phosphate (18) had the best activity in replicon assay. Phosphoramidates (18-21) achieved a significant improvement in antiviral potency over the parent nucleoside (1) with no increase in cytotoxicity...
  52. ncbi request reprint Phosphoramidate derivatives of 2',5'-dideoxyadenosine as potential inhibitors of the EDHF phenomenon
    F Gavazza
    Welsh School of Pharmacy, Redwood Building, Cardiff University, Cardiff CFIO 3XF, UK
    Nucleosides Nucleotides Nucleic Acids 24:553-5. 2005
    ..In the present work a new series of 2',5'-ddA phosphoramidates has been synthesized, representing the first example of phosphoramidate protide not at the 5'-position...
  53. ncbi request reprint Naphthyl phosphoramidate derivatives of BVdU as potential anticancer agents: design, synthesis and biological evaluation
    C Congiatu
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Nucleosides Nucleotides Nucleic Acids 24:485-9. 2005
    ..We report in this work a new series of derivatives containing naphthol as aryl masking group on the phosphate moiety, which has shown a significant increase in anticancer activity in preliminary biological evaluations...
  54. doi request reprint Phosphoramidates of 2'-beta-D-arabinouridine (AraU) as phosphate prodrugs; design, synthesis, in vitro activity and metabolism
    Youcef Mehellou
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK
    Bioorg Med Chem 18:2439-46. 2010
    ..These findings may explain the poor antiviral/cytostatic potential of the prodrugs...
  55. ncbi request reprint Novel potential anticancer naphthyl phosphoramidates of BVdU: separation of diastereoisomers and assignment of the absolute configuration of the phosphorus center
    Costantino Congiatu
    Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3XF, UK
    J Med Chem 49:452-5. 2006
    ..Through computational and NMR studies, the absolute stereochemistry of the phosphorus center of the two diastereoisomers has been suggested...
  56. ncbi request reprint Application of the phosphoramidate ProTide approach to 4'-azidouridine confers sub-micromolar potency versus hepatitis C virus on an inactive nucleoside
    Plinio Perrone
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    J Med Chem 50:1840-9. 2007
    ..The generic message is that ProTide synthesis from inactive parent nucleosides may be a warranted drug discovery strategy...
  57. ncbi request reprint Molecular modelling studies on the binding of some protides to the putative human phosphoramidase Hint1
    C Congiatu
    Welsh School of Pharmacy, Cardiff University, Cardiff, United Kingdom
    Nucleosides Nucleotides Nucleic Acids 26:1121-4. 2007
    ..Herein, we report our preliminary analysis based on docking studies of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU) related aminoacyl phosphates with Hint1 and the effect of the amino acid moiety on the enzyme-substrate binding affinity...
  58. ncbi request reprint Topical delivery of retinyl ascorbate co-drug: 6. Determination of toxic dose and antioxidant activity in cultured human epidermal keratinocytes
    K Abdulmajed
    Welsh School of Pharmacy, Cardiff University, UK
    Pharmazie 60:794-5. 2005
    ..RA-AsA exhibited toxic effects at concentrations >6 microM. The findings indicate to the potency of RA-AsA as free radical scavenger and cell proliferation regulator...
  59. doi request reprint An investigation into the anti-HIV activity of 2',3'-didehydro-2',3'-dideoxyuridine (d4U) and 2',3'-dideoxyuridine (ddU) phosphoramidate 'ProTide' derivatives
    Youcef Mehellou
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, UK CF10 3NB
    Org Biomol Chem 7:2548-53. 2009
    ..Thus, a poor second and/or third phosphorylation step may be the most likely reason for the virtual lack of anti-HIV activity in this case...
  60. ncbi request reprint Design, synthesis and evaluation of a novel double pro-drug: INX-08189. A new clinical candidate for hepatitis C virus
    Christopher McGuigan
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK
    Bioorg Med Chem Lett 20:4850-4. 2010
    ..INX-08189 has completed investigational new drug enabling studies and has been progressed into human clinical trials for the treatment of chronic HCV infection...
  61. ncbi request reprint Bicyclic nucleoside inhibitors of Varicella-Zoster virus: the effect of branching in the p-alkylphenyl side chain
    Giovanna Luoni
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    Bioorg Med Chem Lett 15:3791-6. 2005
    ....
  62. ncbi request reprint Stereoselective and concentration-dependent polarized epithelial permeability of a series of phosphoramidate triester prodrugs of d4T: an in vitro study in Caco-2 and Madin-Darby canine kidney cell monolayers
    Dario Siccardi
    Welsh School of Pharmacy, University of Wales Cardiff, King Edward VII Ave, Cardiff CF10 3XF, Wales
    J Pharmacol Exp Ther 307:1112-9. 2003
    ....
  63. pmc The application of phosphoramidate protide technology to acyclovir confers anti-HIV inhibition
    Marco Derudas
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    J Med Chem 52:5520-30. 2009
    ..ProTides showing diminished carboxypeptidase lability translated to poor anti-HIV agents and vice versa, so the assay became predictive...
  64. doi request reprint The design, synthesis and antiviral evaluation of a series of 5-trimethylsilyl-1-beta-D-(arabinofuranosyl)uracil phosphoramidate ProTides
    Youcef Mehellou
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Antivir Chem Chemother 20:153-60. 2010
    ..Our ProTide method allows the direct use of masked membrane-soluble preformed nucleoside phosphates, bypassing the need for the initial phosphorylation step. We herein applied it to some novel 5-trimethylsilyl arabinosyl uridines...
  65. doi request reprint Application of the phosphoramidate ProTide approach to the antiviral drug ribavirin
    Marco Derudas
    Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3NB, UK
    Bioorg Med Chem 18:2748-55. 2010
    ....
  66. ncbi request reprint Bicyclic anti-VZV nucleosides: thieno analogues bearing an alkylphenyl side chain have reduced antiviral activity
    Annette Angell
    Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK
    Bioorg Med Chem Lett 14:2397-9. 2004
    ..While the alkyl chain analogues were shown to retain full antiviral activity against VZV, these new analogues did not when compared to their furo parent nucleosides...
  67. pmc Enhanced inhibition of the EDHF phenomenon by a phenyl methoxyalaninyl phosphoramidate derivative of dideoxyadenosine
    Tudor M Griffith
    Department of Diagnostic Radiology, Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN
    Br J Pharmacol 142:27-30. 2004
    ....
  68. ncbi request reprint Non-nucleoside structures retain full anti-HCMV potency of the dideoxy furanopyrimidine family
    Olivier Bidet
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Antivir Chem Chemother 15:329-32. 2004
    ..We now find that the fully deoxygenated 2',3',5'-trideoxy analogue is fully antivirally active. This is taken as proof that these agents act by a novel non-nucleoside mechanism of action...
  69. ncbi request reprint Topical delivery of retinyl ascorbate co-drug. 2. Comparative skin tissue and keratin binding studies
    K Abdulmajed
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Skin Pharmacol Physiol 17:274-82. 2004
    ..For highly polar AsA, lipid content decreased the binding, suggesting that the lipid reduced the strong polar interactions with skin protein/keratin...
  70. ncbi request reprint The differential expression of hCNT1 and hENT1 i n breast cancer and the possible impact on breast cancer therapy
    Jane Lane
    School of Medicine, Cardiff University, Cardiff, Wales, United Kingdom
    J Exp Ther Oncol 8:203-10. 2010
    ..The level of expression of CNT1 was closely linked to the cell's responsiveness to chemotherapeutic treatments...
  71. ncbi request reprint Preferential pi-pi complexation between tamoxifen and borage oil/gamma linolenic acid: transcutaneous delivery and NMR spectral modulation
    Charles M Heard
    Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3XF, UK
    Int J Pharm 302:47-55. 2005
    ..The mechanism for the permeation of intact complexes across skin remains to be elucidated...
  72. ncbi request reprint Bicyclic pyrimidine nucleoside analogues (BCNAs) as highly selective and potent inhibitors of varicella-zoster virus replication
    Jan Balzarini
    Rega Institute for Medical Research, K U Leuven, B 3000 Leuven, Belgium
    J Antimicrob Chemother 50:5-9. 2002
    ..Given the above-mentioned favourable properties, BCNAs may represent a promising novel class of highly selective anti-VZV drugs that should be further pursued for clinical application...
  73. ncbi request reprint Aryloxy phosphoramidate triesters as pro-tides
    Dominique Cahard
    UMR 6014 CNRS, Universite de Rouen, Mont Saint Aignan Cedex, France
    Mini Rev Med Chem 4:371-81. 2004
    ..The review covers the discovery of such aryl phosphoramidates, their mechanism of action and structure-activity relationships. The application of this strategy to a range of antiviral nucleosides is highlighted...
  74. ncbi request reprint Phosphoramidate protides of 2',3'-dideoxy-3'-fluoroadenosine and related nucleosides with potent activity against HIV and HBV
    Kristjan S Gudmundsson
    Division of Chemistry, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA
    Nucleosides Nucleotides Nucleic Acids 22:1953-61. 2003
    ..Especially marked was the improvement in potency of phosphoramidate protides of 2',3'-dideoxy-3'-fluoroadenosine against both HIV and HBV...
  75. ncbi request reprint Phosphoramidate protides of carbocyclic 2',3'-dideoxy-2',3'-didehydro-7-deazaadenosine with potent activity against HIV and HBV
    Kristjan S Gudmundsson
    Division of Chemistry, GlaxoSmithKline, Research Triangle Park, North Carolina, USA
    Nucleosides Nucleotides Nucleic Acids 23:1929-37. 2004
    ..Several of these protides showed significantly improved antiviral potency over the parent nucleosides against both HIV and HBV...
  76. ncbi request reprint Specific recognition of the bicyclic pyrimidine nucleoside analogs, a new class of highly potent and selective inhibitors of varicella-zoster virus (VZV), by the VZV-encoded thymidine kinase
    Rebecca Sienaert
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
    Mol Pharmacol 61:249-54. 2002
    ..Our observations may account for the unprecedented specificity of BCNAs as anti-VZV agents...
  77. doi request reprint Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in herpesvirus-infected human tissues
    Andrea Lisco
    Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Cell Host Microbe 4:260-70. 2008
    ..These data suggest that ACV anti-HIV-1 activity may contribute to the response of HIV/HHV-coinfected patients to ACV treatment and could guide strategies for the development of new HIV-1 RT inhibitors...