Abstract

The research described in this proposal can be segmented into four distinct parts. These include: (a) the development of two complementary synthetic protocols which permit the stereoselective construction of a wide variety of 2'-deoxyribose and 2',3'- dideoxyribose derivatives of nucleotides from inexpensive, non- carbohydrate precursors; (b) the development of a synthetic protocol which permits the rapid, stereoselective construction of oxetane nucleosides from inexpensive, non-carbohydrate precursors; (c) the demonstration of the viability of this research by utilizing these synthetic protocols to prepare a number of nucleosides which exhibit significant anti-HIV activity; (d) the preparation of novel nucleoside analogues which may exhibit significant anti-HIV activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI028731-02
Application #
3143243
Study Section
Special Emphasis Panel (ARR (V1))
Project Start
1989-07-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Miller, Eric J; Jecs, Edgars; Truax, Valarie M et al. (2018) Discovery of Tetrahydroisoquinoline-Containing CXCR4 Antagonists with Improved in Vitro ADMET Properties. J Med Chem 61:946-979
Wilson, Robert J; Jecs, Edgars; Miller, Eric J et al. (2018) Synthesis and SAR of 1,2,3,4-Tetrahydroisoquinoline-Based CXCR4 Antagonists. ACS Med Chem Lett 9:17-22
Liotta, Dennis C; Painter, George R (2016) Discovery and Development of the Anti-Human Immunodeficiency Virus Drug, Emtricitabine (Emtriva, FTC). Acc Chem Res 49:2091-2098
Muthu, Pravin; Lutz, Stefan (2016) Quantitative Detection of Nucleoside Analogues by Multi-enzyme Biosensors using Time-Resolved Kinetic Measurements. ChemMedChem 11:660-6
Giesler, Kyle E; Liotta, Dennis C (2016) Next-Generation Reduction Sensitive Lipid Conjugates of Tenofovir: Antiviral Activity and Mechanism of Release. J Med Chem 59:10244-10252
Kim, Michelle B; Giesler, Kyle E; Tahirovic, Yesim A et al. (2016) CCR5 receptor antagonists in preclinical to phase II clinical development for treatment of HIV. Expert Opin Investig Drugs 25:1377-1392
Giesler, Kyle E; Marengo, Jose; Liotta, Dennis C (2016) Reduction Sensitive Lipid Conjugates of Tenofovir: Synthesis, Stability, and Antiviral Activity. J Med Chem 59:7097-110
Cox, Bryan D; Prosser, Anthony R; Sun, Yongnian et al. (2015) Pyrazolo-Piperidines Exhibit Dual Inhibition of CCR5/CXCR4 HIV Entry and Reverse Transcriptase. ACS Med Chem Lett 6:753-7
Zhao, Huanyu; Prosser, Anthony R; Liotta, Dennis C et al. (2015) Discovery of novel N-aryl piperazine CXCR4 antagonists. Bioorg Med Chem Lett 25:4950-5
Cox, Bryan D; Prosser, Anthony R; Katzman, Brooke M et al. (2014) Anti-HIV small-molecule binding in the peptide subpocket of the CXCR4:CVX15 crystal structure. Chembiochem 15:1614-20

Showing the most recent 10 out of 21 publications