BIOMAT Database Logo BIOMAT Database Logo

Asymmetric synthesis of 1,3-dioxolane-pyrimidine nucleosides and their anti-HIV activity. 1992

H O Kim, and S K Ahn, and A J Alves, and J W Beach, and L S Jeong, and B G Choi, and P Van Roey, and R F Schinazi, and C K Chu
Department of Medicinal Chemistry, College of Pharmacy, University of Georgia, Athens 30602.

In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV agents, various enantiomerically pure dioxolane-pyrimidine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 8 has been synthesized in nine steps from 1,6-anhydro-D-mannose (1), which was condensed with 5-substituted pyrimidines to obtain various dioxolane-pyrimidine nucleosides. Upon evaluation of these compounds, cytosine derivative 19 was found to exhibit the most potent anti-HIV agent although it is the most toxic. The order of anti-HIV potency was as follows: cytosine (beta-isomer) greater than thymine greater than cytosine (alpha-isomer) greater than 5-chlorouracil greater than 5-bromouracil greater than 5-fluorouracil derivatives. Uracil, 5-methylcytosine, and 5-iodouracil derivatives were found to be inactive. Interestingly, alpha-isomer 20 showed good anti-HIV activity without cytotoxicity. As expected, other alpha-isomers did not exhibit any significant antiviral activity. (-)-Dioxolane-T was 5-fold less effective against AZT-resistant virus than AZT-sensitive virus.

UI MeSH Term Description Entries
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D011741 Pyrimidine Nucleosides Pyrimidines with a RIBOSE attached that can be phosphorylated to PYRIMIDINE NUCLEOTIDES. Nucleosides, Pyrimidine
D003596 Cytosine A pyrimidine base that is a fundamental unit of nucleic acids.
D004148 Dioxolanes
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
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

Related Publications

H O Kim, and S K Ahn, and A J Alves, and J W Beach, and L S Jeong, and B G Choi, and P Van Roey, and R F Schinazi, and C K Chu
Synthesis and anti-HIV activity of C4-modified pyrimidine nucleosides.
January 1999, Farmaco (Societa chimica italiana : 1989),
H O Kim, and S K Ahn, and A J Alves, and J W Beach, and L S Jeong, and B G Choi, and P Van Roey, and R F Schinazi, and C K Chu
Synthesis and anti-HIV activity of several 2'-fluoro-containing pyrimidine nucleosides.
August 1990, Journal of medicinal chemistry,
H O Kim, and S K Ahn, and A J Alves, and J W Beach, and L S Jeong, and B G Choi, and P Van Roey, and R F Schinazi, and C K Chu
Synthesis and anti-HIV activity of 4'-modified cyclopentenyl pyrimidine C-nucleosides.
April 2009, Nucleosides, nucleotides & nucleic acids,
H O Kim, and S K Ahn, and A J Alves, and J W Beach, and L S Jeong, and B G Choi, and P Van Roey, and R F Schinazi, and C K Chu
Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: a comparison of phosphonates and corresponding nucleosides.
January 2007, Nucleosides, nucleotides & nucleic acids,
H O Kim, and S K Ahn, and A J Alves, and J W Beach, and L S Jeong, and B G Choi, and P Van Roey, and R F Schinazi, and C K Chu
Synthesis and anti-HIV activity of different sugar-modified pyrimidine and purine nucleosides.
October 1988, Journal of medicinal chemistry,
H O Kim, and S K Ahn, and A J Alves, and J W Beach, and L S Jeong, and B G Choi, and P Van Roey, and R F Schinazi, and C K Chu
Synthesis and antiviral activities of N-9-oxypurine 1,3-dioxolane and 1,3-oxathiolane nucleosides.
October 2000, Bioorganic & medicinal chemistry letters,
H O Kim, and S K Ahn, and A J Alves, and J W Beach, and L S Jeong, and B G Choi, and P Van Roey, and R F Schinazi, and C K Chu
Anti-HIV-1 activities of 1,3-dioxolane guanine and 2,6-diaminopurine dioxolane.
January 1999, Nucleosides & nucleotides,
H O Kim, and S K Ahn, and A J Alves, and J W Beach, and L S Jeong, and B G Choi, and P Van Roey, and R F Schinazi, and C K Chu
Simple synthesis and anti-HIV activity of novel 3'-vinyl branched apiosyl pyrimidine nucleosides.
January 2006, Nucleosides, nucleotides & nucleic acids,
H O Kim, and S K Ahn, and A J Alves, and J W Beach, and L S Jeong, and B G Choi, and P Van Roey, and R F Schinazi, and C K Chu
Synthesis and anti-HIV activity of (-)-beta-D-(2R,4R)-1,3-dioxolane-2,6-diamino purine (DAPD) (amdoxovir) and (-)-beta-D-(2R,4R)-1,3-dioxolane guanosine (DXG) prodrugs.
September 2007, Antiviral research,
H O Kim, and S K Ahn, and A J Alves, and J W Beach, and L S Jeong, and B G Choi, and P Van Roey, and R F Schinazi, and C K Chu
Asymmetric synthesis and biological evaluation of beta-L-(2R,5S)- and alpha-L-(2R,5R)-1,3-oxathiolane-pyrimidine and -purine nucleosides as potential anti-HIV agents.
January 1993, Journal of medicinal chemistry,
Copied contents to your clipboard!