December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Phospholipid Prodrugs of Nucleosides for Intravitreal Injection: Synthesis of Hexadecyloxypropyl-phospho-Ara G for the Treatment of Proliferative Vitreoretinopathy
Author Affiliations & Notes
  • JR Beadle
    Department of Medicine University of California-San Diego and the VA Medical Center La Jolla CA
  • L-Y Cheng
    Department of Opthalmology Shiley Eye Center UCSD La Jolla CA
  • KY Hostetler
    Department of Medicine University of California-San Diego and the VA Medical Center La Jolla CA
  • WR Freeman
    Department of Opthalmology Shiley Eye Center UCSD La Jolla CA
  • Footnotes
    Commercial Relationships    J.R. Beadle, Univ. of California, San Diego P; L. Cheng, None; K.Y. Hostetler, Univ. of California, San Diego P; W.R. Freeman, None. Grant Identification: Support: NIH Grant EY07366
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 2311. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      JR Beadle, L-Y Cheng, KY Hostetler, WR Freeman; Phospholipid Prodrugs of Nucleosides for Intravitreal Injection: Synthesis of Hexadecyloxypropyl-phospho-Ara G for the Treatment of Proliferative Vitreoretinopathy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2311.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Abstract: : Purpose: To prepare an injectable phopholipid prodrug of the antiproliferative agent 9-(ß-D-arabinofuranosyl)guanine (Ara G) for evaluation as a long-lasting therapy against proliferative vitreoretinopathy (PVR). Methods: Previous studies in experimental models showed that hexadecyloxypropyl-phospho-ganciclovir provides sustained intravitreal release of ganciclovir. To extend this drug delivery strategy to Ara G and the treatment of PVR, the synthesis of the related compound hexadecyloxypropyl-phospho-Ara G (HDP-P-Ara G) was undertaken. Results: The reactive groups of guanosine were blocked with appropriate protecting groups and the 2'-hydroxyl was converted to trifluoromethanesulfonate. Reaction of the triflate intermediate with lithium acetate, followed by partial deblocking, provided the key blocked Ara G derivative 1 (see below). Compound 1 was then coupled to hexadecyloxypropylphosphate (DCC, pyridine). Complete deblocking afforded the target compound, HDP-P-Ara G, as a white crystalline solid. Conclusion: A procedure was developed for the synthesis of HDP-P-Ara G from the readily available starting material guanosine. Intravitreal injection of crystalline HDP-P-Ara G may provide a long-lasting antiproliferative effect for the treatment of PVR.  

Keywords: 524 proliferative vitreoretinopathy • 390 drug toxicity/drug effects • 567 retinal pigment epithelium 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×