2-amino-9-(3-azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)-6-substituted-9H-purines: synthesis and anti-HIV activity.
A series of 2-amino-9-(3-azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)-6- substituted-9H-purines was synthesized and tested for the ability to protect MT4 cells from the cytopathic effect of HIV-1IIIB. These compounds were prepared by a combination of chemical and enzymatic reactions. Some of the nucleoside analogs with 6-alkoxy, 6-alkylamino, or 6-arylamino substituents were active against HIV-1IIIB. Their IC50 values were in the range of 2-60 microM. In contrast, analogs with 6-thio, 6-alkylthio, 6-methyl, or 6-carbonitrile substituents did not protect cells from the cytopathic effect of HIV infection.
Freeman
G A
GA
Burroughs Wellcome Co., Division of Organic Chemistry, Research Triangle Park, NC 27709, USA.
Shaver
S R
SR
Rideout
J L
JL
Short
S A
SA
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002461:Cell Line, Transformed / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015224:Dideoxynucleosides / Q000737:chemistry*; D006151:Guanosine / Q000031:analogs & derivatives / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007778:Lactobacillus / Q000201:enzymology; D010430:Pentosyltransferases / Q000378:metabolism; D011687:Purines / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology; D013936:Thymidine / Q000737:chemistry / Q000378:metabolism; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
C098203:2-amino-9-(3-azido-2,3-dideoxy-erythro-pentofuranosyl)-6-(1-pyrrolidinyl)-9H-purine; D000998:Antiviral Agents; D015224:Dideoxynucleosides; D011687:Purines; D006151:Guanosine; D015215:Zidovudine; C051073:3'-azido-2',3'-dideoxyguanosine; C031872:triacetylguanosine; D010430:Pentosyltransferases; C021888:nucleoside deoxyribosyltransferase; D013936:Thymidine; C030985:purine