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By C.K. Chu

• updated evaluation at the chemistry and biology of nucleosides • glossy man made method • complete insurance of antiviral nucleosidesThis ebook summarizes the hot advances in nucleosides chemistry and chemotherapy over the last 10-15 years. It covers lately came upon nucleoside antiviral brokers, their healing facets and biochemistry, and in addition broad stories on their chiral synthesis.

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Herdewijn, P. Synthesis and antiviral activity of 5-thien-2-yl-2'-deoxyuridines. J. Med. Chem. 1993, 36, 538-543. 20. ; Lee, C. -C; Chu, C. K. Structure-activity relationships of (F)-5-(2-bromovinyl)uracil nucleosides and related analogs as anti-herpesvirus agents. /. Med. Chem. 2000, 43, 2538-2546. 21. Bryant, M. ; Bridges, E. ; Faraj. ; Loi, A. ; Imbach, J. ; Schinazi, R. ; Sonmiadossi, J. -P. Antiviral L-nucleosides specific for hepatitis B virus infection. Antimicrob.

294 H D P - P - G C V has also been evaluated in HCMV-infected human lung fibroblasts. 6 |LiM. 50 G. Gumina, Y. Choi and C. K. Chu -0(CH2)i5CH3 O (XX. R 168 (VCV) 169 (HDP-P-ACV), R = H 170 (HDP-P-GCV), R = CH2OH Figure 66. Prodrugs of acyclovir and ganciclovir. ^^^ The alkoxyalkyl esters 1-O-hexadecyloxypropyl-cidofovir (HDP-CDV, 171, Figure 67) and 1-0-octadecyloxyethyl-cidofovir (ODE-CDV, 172) and their cyclic analogs HDP-cCDV (173) and ODE-cCDV (174) were more active against HSV-1, HSV-2, HCMV, VZV, EBV and human herpes virus type 6 (HHV-6) and 8 (HHV-8) than the parents compounds, with the cidofovir analogs generally more active than the cyclic ones.

D4G and its prodrug cyclo-d4G. 2'- or 3'-Substituted d4N analogs also retain their antiviral activity. In particular, introduction of a fluorine atom at the 2'-position produces compounds with anti-HIV and anti-HBV activity (Figure 34). Among the 2'-fluorinated d4N analogs, cytosine derivative D-Fd4C (90) shows moderate anti-HIV activity with significant toxicity. ^^'^^^ Most of the purine analogs have moderate to potent anti-HIV activity. ^^^ Among these compounds, cytosine (92) and 5-F-cytosine (93) exhibit potent anti-HIV-1 and anti-HBV activity.

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