Abstract

Despite significant advances in the treatment of HIV infection, there are a number of unresolved issues in AIDS chemotherapy, including viral resistance, viral reservoir, salvage therapy and potential elimination of the virus. In order to solve all these problems, the critical need in the future will be the discovery of more potent and selective new anti-HIV regimens with different patterns of resistance than approved drugs. This proposal is a continuation of ongoing drug discovery efforts in the area of antiviral nucleosides at the University of Georgia and the Emory University/VA Medical Center. The investigators propose to explore the chemistry and virology of the following classes of mainly L-nucleosides: (1) oxaselenolane nucleosides; (2) fluorinated L-D4N; (3) 2-substituted L-carbocyclic nucleosides; (4) L-apionucleosides; (5) L-oxetanocin analogs; (6) cyclobutane carbocyclic L-nucleosides; (7) conformationally restricted endo-cyclopropropylnucleosides; (8) homo- cyclopropylcarbocyclic nucleosides.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI032351-08A1
Application #
2873745
Study Section
Special Emphasis Panel (ZRG1-AARR-3 (05))
Program Officer
Litterst, Charles L
Project Start
1992-01-01
Project End
2002-02-28
Budget Start
1999-03-15
Budget End
2000-02-29
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Georgia
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
City
Athens
State
GA
Country
United States
Zip Code
30602

  Publications

Wang, Jianing; Jin, Yunho; Rapp, Kimberly L et al. (2007) D- and L-2',3'-didehydro-2',3'-dideoxy-3'-fluoro-carbocyclic nucleosides: synthesis, anti-HIV activity and mechanism of resistance. J Med Chem 50:1828-39
Asif, Ghazia; Hurwitz, Selwyn J; Obikhod, Aleksandr et al. (2007) Pharmacokinetics of the anti-human immunodeficiency virus agent 1-(beta-D-dioxolane)thymine in rhesus monkeys. Antimicrob Agents Chemother 51:2424-9
Choo, Hyunah; Chen, Xin; Yadav, Vikas et al. (2006) Synthesis and anti-HIV activity of D- and L-thietanose nucleosides. J Med Chem 49:1635-47
Amblard, Franck; Delinsky, David; Arbiser, Jack L et al. (2006) Facile purification of honokiol and its antiviral and cytotoxic properties. J Med Chem 49:3426-7
Zhang, Hongwang; Schinazi, Raymond F; Chu, Chung K (2006) Synthesis of neplanocin F analogues as potential antiviral agents. Bioorg Med Chem 14:8314-22
Shi, Junxing; Du, Jinfa; Ma, Tianwei et al. (2005) Synthesis and in vitro anti-HCV activity of beta-D- and 1-2'-deoxy-2'-fluororibonucleosides. Nucleosides Nucleotides Nucleic Acids 24:875-9
Ray, Adrian S; Hernandez-Santiago, Brenda I; Mathew, Judy S et al. (2005) Mechanism of anti-human immunodeficiency virus activity of beta-D-6-cyclopropylamino-2',3'-didehydro-2',3'-dideoxyguanosine. Antimicrob Agents Chemother 49:1994-2001
Wang, Jianing; Jin, Yunho; Rapp, Kimberly L et al. (2005) Synthesis, antiviral activity, and mechanism of drug resistance of D- and L-2',3'-didehydro-2',3'-dideoxy-2'-fluorocarbocyclic nucleosides. J Med Chem 48:3736-48
Gadthula, Srinivas; Chu, Chung K; Schinazi, Raymond F (2005) Synthesis and anti-HIV activity of beta-D-3'-azido-2',3'-unsaturated nucleosides and beta-D-3'-azido-3'-deoxyribofuranosylnucleosides. Nucleosides Nucleotides Nucleic Acids 24:1707-27
Rais, Reem H; Al Safarjalani, Omar N; Yadav, Vikas et al. (2005) 6-Benzylthioinosine analogues as subversive substrate of Toxoplasma gondii adenosine kinase: activities and selective toxicities. Biochem Pharmacol 69:1409-19

Showing the most recent 10 out of 87 publications