Synthesis and biological activities of 2-pyrimidinone nucleosides. 2. 5-Halo-2-pyrimidinone 2'-deoxyribonucleosides.
1-(2-Deoxy-beta-D-ribofuranosyl)-5-bromo-2-pyrimidinone (BrPdR) and 1-(2-deoxy-beta-D-ribofuranosyl)-5-iodo-2-pyrimidinone (IPdR) have been synthesized by condensation of the appropriate silylated bases 2a and 2b, respectively, with 3,5-bis-O-(p-chlorobenzoyl)-2-deoxy-alpha-D-ribofuranosyl chloride (8) in 1,2-dichloroethane, in the presence of SnCl4, followed by separation of the anomeric blocked nucleosides via column chromatography and subsequent deprotection with methanolic ammonia. Both BrPdR and IPdR exhibited significant antiherpes activities against various strains of HSV-1 and HSV-2, the latter compound (IPdR) showing the higher activity as well as the stronger binding to the virus-specific thymidine kinase.
Efange
S M
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Alessi
E M
EM
Shih
H C
HC
Cheng
Y C
YC
Bardos
T J
TJ
D000818:Animals; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D003564:Cytidine Deaminase; D004352:Drug Resistance, Microbial; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009700:Nucleoside Deaminases / Q000378:metabolism; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects* / Q000201:enzymology; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors; D014001:Tin; D017971:Tin Compounds
D011741:Pyrimidine Nucleosides; D017971:Tin Compounds; C023599:stannous chloride; C045889:ropidoxuridine; D014001:Tin; C045890:1-(2-deoxy-beta-ribofuranosyl)-5-bromo-2-pyrimidinone; D013937:Thymidine Kinase; D009700:Nucleoside Deaminases; D003564:Cytidine Deaminase; C011530:deoxycytidine deaminase