BIOMAT Database Logo BIOMAT Database Logo

Synthesis and anti-HIV-1 evaluation of phosphonates which mimic the 5'-monophosphate of 4'-branched 2',3'-didehydro-2',3'-dideoxy nucleosides. 2010

Yutaka Kubota, and Nobuhide Ishizaki, and Kazuhiro Haraguchi, and Takayuki Hamasaki, and Masanori Baba, and Hiromichi Tanaka
School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. y-kubota@pharm.showa-u.ac.jp

Synthesis of the 4'-ethynyl and 4'-cyano phosphonates 8-11, which mimic the 5'-monophosphate of 4'-branched 2',3'-didehydro-2',3'-dideoxy nucleosides, was investigated by employing the 3',4'-unsaturated nucleosides (13 and 28) as the starting material. The synthesis was initiated by the electrophilic addition of NIS/(EtO)(2)P(O)CH(2)OH to these unsaturated nucleosides. After introduction of the 2',3'-double bond, the 4'-hydroxylmethyl group of the resulting adducts was transformed into the ethynyl or cyano group. While the 4'-cyano phosphonates 9 and 11 were not sufficiently stable to be isolated, the 4'-ethynyl counterparts (8 and 10) were obtained as their mono-ammonium salts. The adenine derivative 8 showed almost comparable anti-HIV-1 activity to that of d4T.

UI MeSH Term Description Entries
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015224 Dideoxynucleosides Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'-triphosphates and act as chain-terminating inhibitors of viral reverse transcription. 2',3'-Dideoxynucleosides,Dideoxyribonucleosides,ddNus,2',3' Dideoxynucleosides
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
D018119 Stavudine A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV. 2',3'-Didehydro-3'-deoxythymidine,D4T,2',3'-Didehydro-2',3'-dideoxythmidine,BMY-27857,Stavudine, Monosodium Salt,Zerit,2',3' Didehydro 3' deoxythymidine,BMY 27857,BMY27857
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV
D063065 Organophosphonates Carbon-containing phosphonic acid compounds. Included under this heading are compounds that have carbon bound to either OXYGEN atom or the PHOSPHOROUS atom of the (P Phosphonate,Phosphonates,Phosphonic Acid Esters,Acid Esters, Phosphonic,Esters, Phosphonic Acid

Related Publications

Yutaka Kubota, and Nobuhide Ishizaki, and Kazuhiro Haraguchi, and Takayuki Hamasaki, and Masanori Baba, and Hiromichi Tanaka
Nucleosides. XVI. The synthesis of 2',3'-dideoxy-3',4'-didehydro nucleosides.
March 1973, The Journal of organic chemistry,
Yutaka Kubota, and Nobuhide Ishizaki, and Kazuhiro Haraguchi, and Takayuki Hamasaki, and Masanori Baba, and Hiromichi Tanaka
Synthesis and anti-HIV activity of carbocyclic 2',3'-didehydro-2',3'-dideoxy 2,6-disubstituted purine nucleosides.
January 1990, Journal of medicinal chemistry,
Yutaka Kubota, and Nobuhide Ishizaki, and Kazuhiro Haraguchi, and Takayuki Hamasaki, and Masanori Baba, and Hiromichi Tanaka
Synthesis of 3'-fluoro-2',3'-dideoxy-2',3'-didehydro-4'-ethynyl-D- and -L-furanosyl nucleosides.
September 2004, The Journal of organic chemistry,
Yutaka Kubota, and Nobuhide Ishizaki, and Kazuhiro Haraguchi, and Takayuki Hamasaki, and Masanori Baba, and Hiromichi Tanaka
D- and L-2',3'-didehydro-2',3'-dideoxy-3'-fluoro-carbocyclic nucleosides: synthesis, anti-HIV activity and mechanism of resistance.
April 2007, Journal of medicinal chemistry,
Yutaka Kubota, and Nobuhide Ishizaki, and Kazuhiro Haraguchi, and Takayuki Hamasaki, and Masanori Baba, and Hiromichi Tanaka
Synthesis and potent anti-HIV activity of L-2',3'-didehydro-2',3'-dideoxy-2'-fluoro-4'-thiocytidine.
January 2002, Organic letters,
Yutaka Kubota, and Nobuhide Ishizaki, and Kazuhiro Haraguchi, and Takayuki Hamasaki, and Masanori Baba, and Hiromichi Tanaka
Stereoselective synthesis of beta-L-2',3'-dideoxy- and L-2',3'-didehydro-2',3'-dideoxy purine nucleosides.
January 1999, Nucleosides & nucleotides,
Yutaka Kubota, and Nobuhide Ishizaki, and Kazuhiro Haraguchi, and Takayuki Hamasaki, and Masanori Baba, and Hiromichi Tanaka
Synthesis and antiviral evaluation of alpha-D-2',3'-didehydro-2',3'-dideoxy-3'-C-hydroxymethyl nucleosides.
January 2001, Nucleic acids research. Supplement (2001),
Yutaka Kubota, and Nobuhide Ishizaki, and Kazuhiro Haraguchi, and Takayuki Hamasaki, and Masanori Baba, and Hiromichi Tanaka
Synthesis and antiviral evaluation of α-D-2',3'-didehydro-2',3'-dideoxy-3'-C-hydroxymethyl nucleosides.
October 2010, Bioorganic & medicinal chemistry letters,
Yutaka Kubota, and Nobuhide Ishizaki, and Kazuhiro Haraguchi, and Takayuki Hamasaki, and Masanori Baba, and Hiromichi Tanaka
3'-Carbon-substituted pyrimidine nucleosides having a 2',3'-dideoxy and 2',3'-didehydro-2',3'-dideoxy structure: synthesis and antiviral evaluation.
January 2006, Antiviral chemistry & chemotherapy,
Yutaka Kubota, and Nobuhide Ishizaki, and Kazuhiro Haraguchi, and Takayuki Hamasaki, and Masanori Baba, and Hiromichi Tanaka
Synthesis of 2',3'-dideoxy-2',3'-didehydro nucleosides via a serendipitous route.
January 2001, Nucleosides, nucleotides & nucleic acids,
Copied contents to your clipboard!