Abstract

New nucleoside and nucleotide analogues will be prepared and studied as antiviral antitumor agents.These compounds will include (i) gem-bis-(hydroxymethyl)methylenecyclopropanes, (ii) cyclicphosphates of gem-bis-(hydroxymethyl) methylenecyclopropanes, (iii) lipophilic phosphoralaninate prodrugs of gem-bis-(hydroxymethyl)methylenecyclopropanes, (iv) 7-(2-amino)purine analogues, (v) phosphonateanalogues of methylenecyclopropanes and (vi) resolution of R and S diastereoisomers of phosphoralaninate methylenecyclopropane prodrugs,synthesis of the respective phosphorothioates and study of stereochemistry of intracellular activation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032779-21
Application #
6748163
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Lees, Robert G
Project Start
1984-07-01
Project End
2005-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
21
Fiscal Year
2004
Total Cost
$186,250
Indirect Cost

  Institution

Name
Wayne State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202

  Publications

Chen, Han; Li, Chengwei; Zemlicka, Jiri et al. (2016) Potency and Stereoselectivity of Cyclopropavir Triphosphate Action on Human Cytomegalovirus DNA Polymerase. Antimicrob Agents Chemother 60:4176-82
Gentry, Brian G; Vollmer, Laura E; Hall, Ellie D et al. (2013) Resistance of human cytomegalovirus to cyclopropavir maps to a base pair deletion in the open reading frame of UL97. Antimicrob Agents Chemother 57:4343-8
Gentry, Brian G; Gentry, Sara N; Jackson, Trachette L et al. (2011) Phosphorylation of antiviral and endogenous nucleotides to di- and triphosphates by guanosine monophosphate kinase. Biochem Pharmacol 81:43-9
Gentry, Brian G; Kamil, Jeremy P; Coen, Donald M et al. (2010) Stereoselective phosphorylation of cyclopropavir by pUL97 and competitive inhibition by maribavir. Antimicrob Agents Chemother 54:3093-8
Zhou, Shaoman; Drach, John C; Prichard, Mark N et al. (2009) (Z)- and (E)-2-(1,2-dihydroxyethyl)methylenecyclopropane analogues of 2'-deoxyadenosine and 2'-deoxyguanosine. Synthesis of all stereoisomers, absolute configuration, and antiviral activity. J Med Chem 52:3397-407
Wu, Zhimeng; Drach, John C; Prichard, Mark N et al. (2009) L-valine ester of cyclopropavir: a new antiviral prodrug. Antivir Chem Chemother 20:37-46
Mhaske, Santosh B; Ksebati, Bashar; Prichard, Mark N et al. (2009) Phosphonate analogues of cyclopropavir phosphates and their E-isomers. Synthesis and antiviral activity. Bioorg Med Chem 17:3892-9
Wu, Zhimeng; Zhou, Shaoman; Zemlicka, Jiri (2009) Stereoselective approach to the Z-isomers of methylenecyclopropane analogues of nucleosides: a new synthesis of antiviral synguanol. Nucleosides Nucleotides Nucleic Acids 28:165-74
Li, Chengwei; Gentry, Brian G; Drach, John C et al. (2009) Synthesis and enantioselectivity of cyclopropavir phosphates for cellular GMP kinase. Nucleosides Nucleotides Nucleic Acids 28:795-808
Randhawa, Parmjeet; Zemlicka, Jiri; Sauerbrei, Andreas et al. (2008) Anti-BK virus activity of nucleoside analogs. Antimicrob Agents Chemother 52:1519-21

Showing the most recent 10 out of 55 publications