Synthesis of 4/5-deoxy-4/5-nucleobase derivatives of 3-O-methyl-D-chiro-inositol as potential antiviral agents. 2006

Tian-Rong Zhan, and Yu-Dao Ma, and Pei-Hong Fan, and Mei Ji, and Hong-Xiang Lou
School of Pharmaceutical Sciences, Shandong University, No.44 West Wenhua Road, Jinan 250012, P.R. China.

Using D-pinitol (= 3-O-methyl-D-chiro-inositol) as starting material, a concise synthesis of 4/5-deoxy-4/5-nucleobase derivatives 11-19 has been achieved. The key intermediate 9 was obtained in good yield via an epoxidation from mono-methanesulfonate of D-pinitol. The process of opening of the epoxide ring in 9 by nucleobases appeared to be regioselective in presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). All the synthesized carbocyclic nucleosides were assayed against several viruses and tumors such as HIV-1, HSV-1, and HSV-2, and lung and bladder cancer. However, only compounds 14b, 14a, 16a, 16b, and 19 showed mild inhibitory effect against human lung cancer cell lines (PG) with IC50 values ranging from 50 to 100 microM, and the other compounds did not exhibit any significant antiviral activity or cytotoxicity even at concentrations up to 200 microM.

UI MeSH Term Description Entries
D007294 Inositol An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. Myoinositol,Chiro-Inositol,Mesoinositol,Chiro Inositol
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009705 Nucleosides Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleoside,Nucleoside Analog,Nucleoside Analogs,Analog, Nucleoside,Analogs, Nucleoside
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003588 Cytopathogenic Effect, Viral Visible morphologic changes in cells infected with viruses. It includes shutdown of cellular RNA and protein synthesis, cell fusion, release of lysosomal enzymes, changes in cell membrane permeability, diffuse changes in intracellular structures, presence of viral inclusion bodies, and chromosomal aberrations. It excludes malignant transformation, which is CELL TRANSFORMATION, VIRAL. Viral cytopathogenic effects provide a valuable method for identifying and classifying the infecting viruses. Cytopathic Effect, Viral,Viral Cytopathogenic Effect,Cytopathic Effects, Viral,Cytopathogenic Effects, Viral,Effect, Viral Cytopathic,Effect, Viral Cytopathogenic,Effects, Viral Cytopathic,Effects, Viral Cytopathogenic,Viral Cytopathic Effect,Viral Cytopathic Effects,Viral Cytopathogenic Effects
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

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