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Synthesis and anti-human immunodeficiency virus (HIV-1) activity of 3'-deoxy-3'-(triazol-1-yl)thymidines and 2',3'-dideoxy-3'-(triazol-1-yl)uridines and inhibition of reverse transcriptase by their 5'-triphosphates. 1990

K Hirota, and H Hosono, and Y Kitade, and Y Maki, and C K Chu, and R F Schinazi, and H Nakane, and K Ono
Department of Medicinal Chemistry, Gifu Pharmaceutical University, Japan.

3'-Deoxy-3'-(1,2,3-triazol-1-yl)thymidines (5a, 6a, 8a, 11a, and 12a) and 2',3'-dideoxy-3'-(1,2,3-triazol-1-yl)uridines (5b, 6b, 8b, 11b, and 12b) were synthesized as cyclic analogues of 3'-azido-3'-deoxythymidine (AZT) and 3'-azido-2',3'-dideoxyuridine (CS-87) by the cyclization of 5'-trityl derivatives (1a, b) of AZT and CS-87 using alpha-ketophosphorus ylides and with acetylenic compounds followed by deprotection of the 5'-trityl group. It was hypothesized that the triazole nitrogen atoms could mimic and distorted azido group. However, no significant activity against human immunodeficiency virus type 1 (HIV-1) was observed with any of these compounds. 5'-Triphosphates (17a and 18a, b), prepared from 5a and 6a, b, were inactive against HIV-1 and Rauscher murine leukemia virus (RLV) reverse transcriptases.

UI MeSH Term Description Entries
D003856 Deoxyuracil Nucleotides Uracil nucleotides which contain deoxyribose as the sugar moiety. Deoxyuridine Phosphates,Nucleotides, Deoxyuracil,Phosphates, Deoxyuridine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D013942 Thymine Nucleotides Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154) Thymidine Phosphates,Nucleotides, Thymine,Phosphates, Thymidine
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D018894 Reverse Transcriptase Inhibitors Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. Reverse Transcriptase Inhibitor,Inhibitors, Reverse Transcriptase,Inhibitor, Reverse Transcriptase,Transcriptase Inhibitor, Reverse

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