BIOMAT Database Logo BIOMAT Database Logo

Phosphoralaninate pronucleotides of pyrimidine methylenecyclopropane analogues of nucleosides: synthesis and antiviral activity. 2005

Amalraj Ambrose, and Jiri Zemlicka, and Earl R Kern, and John C Drach, and Elizabeth Gullen, and Yung-Chi Cheng
Department of Chemistry, Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201-1379, USA.

The Z- and E-thymine and cytosine pronucleotides 3d, 4d, 3e, and 4e of methylenecyclopropane nucleosides analogues were synthesized, evaluated for their antiviral activity against human cytomegalovirus (HCMV), herpes simplex virus 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), human immunodeficiency virus type 1 (HSV-1), and hepatitis B virus (HBV) and their potency was compared with the parent compounds 1d, 2d, 1e, and 2e. Prodrugs 3d and 4d were obtained by phosphorylation of parent analogues 1d or 2d with reagent 8. A similar phosphorylation of N4-benzoylcytosine methylenecyclopropanes 9a and 9b gave intermediates 11a and 11b. Deprotection with hydrazine in pyridine-acetic acid gave pronucleotides 3e and 4e. The Z-cytosine analogue 3e was active against HCMV and EBV The cytosine E-isomer 4e was moderately effective against EBV.

UI MeSH Term Description Entries
D009705 Nucleosides Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleoside,Nucleoside Analog,Nucleoside Analogs,Analog, Nucleoside,Analogs, Nucleoside
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003521 Cyclopropanes Three-carbon cycloparaffin cyclopropane (the structural formula (CH2)3) and its derivatives.
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
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D014780 Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Animal Viruses,Zoophaginae,Animal Virus,Virus,Virus, Animal,Viruses, Animal

Related Publications

Amalraj Ambrose, and Jiri Zemlicka, and Earl R Kern, and John C Drach, and Elizabeth Gullen, and Yung-Chi Cheng
Synthesis and antiviral activity of phosphoralaninate derivatives of methylenecyclopropane analogues of nucleosides.
August 1999, Antiviral research,
Amalraj Ambrose, and Jiri Zemlicka, and Earl R Kern, and John C Drach, and Elizabeth Gullen, and Yung-Chi Cheng
Nucleotides and pronucleotides of 2,2-bis(hydroxymethyl)methylenecyclopropane analogues of purine nucleosides: synthesis and antiviral activity.
January 2005, Journal of medicinal chemistry,
Amalraj Ambrose, and Jiri Zemlicka, and Earl R Kern, and John C Drach, and Elizabeth Gullen, and Yung-Chi Cheng
Synthesis, antiviral, and antitumor activity of 2-substituted purine methylenecyclopropane analogues of nucleosides.
February 2006, Bioorganic & medicinal chemistry,
Amalraj Ambrose, and Jiri Zemlicka, and Earl R Kern, and John C Drach, and Elizabeth Gullen, and Yung-Chi Cheng
Synthesis and antiviral activity of certain second generation methylenecyclopropane nucleosides.
June 2012, Bioorganic & medicinal chemistry,
Amalraj Ambrose, and Jiri Zemlicka, and Earl R Kern, and John C Drach, and Elizabeth Gullen, and Yung-Chi Cheng
Synthesis of Cyclic and Acyclic Pyrimidine Nucleosides Analogues with Anticipated Antiviral Activity.
June 2018, Acta chimica Slovenica,
Amalraj Ambrose, and Jiri Zemlicka, and Earl R Kern, and John C Drach, and Elizabeth Gullen, and Yung-Chi Cheng
Synthesis and biological activity of 2-aminopurine methylenecyclopropane analogues of nucleosides.
January 2003, Nucleosides, nucleotides & nucleic acids,
Amalraj Ambrose, and Jiri Zemlicka, and Earl R Kern, and John C Drach, and Elizabeth Gullen, and Yung-Chi Cheng
Synthesis and biological activity of 2-aminopurine methylenecyclopropane analogues of nucleosides.
February 2003, Nucleosides, nucleotides & nucleic acids,
Amalraj Ambrose, and Jiri Zemlicka, and Earl R Kern, and John C Drach, and Elizabeth Gullen, and Yung-Chi Cheng
In vitro activities of methylenecyclopropane analogues of nucleosides and their phosphoralaninate prodrugs against cytomegalovirus and other herpesvirus infections.
June 2000, Antimicrobial agents and chemotherapy,
Amalraj Ambrose, and Jiri Zemlicka, and Earl R Kern, and John C Drach, and Elizabeth Gullen, and Yung-Chi Cheng
Synthesis of 2,2,3-tris(hydroxymethyl)methylenecyclopropane analogues of nucleosides.
January 2007, Nucleosides, nucleotides & nucleic acids,
Amalraj Ambrose, and Jiri Zemlicka, and Earl R Kern, and John C Drach, and Elizabeth Gullen, and Yung-Chi Cheng
Methylene-gem-difluorocyclopropane analogues of nucleosides: synthesis, cyclopropene-methylenecyclopropane rearrangement, and biological activity.
November 2001, Journal of medicinal chemistry,
Copied contents to your clipboard!