99776-29-1Relevant academic research and scientific papers
Novel open-chain nucleotides imitating 2',3'-dideoxy-2',3'- didehydronucleotides: Synthesis and substrate properties toward DNA polymerases
Shirokova,Tarussova,Shipitsin,Semizarov,Hieber,Krayevsky
, p. 749 - 751 (2007/10/02)
A new series of acyclic nucleotide diphosphates was synthesized and evaluated as potential inbibitors of HIV reverse transcriptases.
Novel acyclic nucleotides and nucleoside 5'-triphosphates imitating 2',3'- dideoxy-2',3'-didehydronucleotides: Synthesis and biological properties
Shirokova,Tarussova,Shipitsin,Semizarov,Krayevsky
, p. 3739 - 3748 (2007/10/02)
A series of pyrophosphoryl (Z)-(phosphonomethoxy)but-2-enyl derivatives of pyrimidines and purines 9a-d and the corresponding phosphonates 10a-d were synthesized. The prepared compounds contain the phosphonate group as an α- phosphate mimic as well as an
Unsaturated and Carbocyclic Nucleoside Analogues: Synthesis, Antitumor, and Antiviral Activity
Phadtare, Shashikant,Kessel, David,Corbett, Thomas H.,Renis, Harold D.,Court, Barbara A.,Zemlicka, Jiri
, p. 421 - 429 (2007/10/02)
A series of unsaturated analogues of nucleosides were prepared and their cytotoxic, antitumor, and antiviral activities were investigated.Alkylation of cytosine with (E)-1,4-dichloro-2-butene gave chloro derivative 2f, which was hydrolyzed to alcohol 2h.Cytosine, adenine, 2-amino-6-chloropurine, thymine, and (Z)-1,4-dichloro-2-butyne gave compounds 4c-f, which, after hydrolysis, afforded alcohols 4a, 4b, 4g, and 4h.Alkenes 4d and 4e were cyclized to heterocycles 12 and 13.Alkylation of 2,6-diaminopurine with 1,4-dichloro-2-butene led to chloro derivative 6a, which was hydrolyzed to alcohol 6b.Allenic isomerization of 6b gave compound 5c.Chloro derivatives 2e-g, 4c-f, 5d, and 6c-e as well as pyrimidine oxacyclopentenes 9c and 9d are slow-acting inhibitors of murine leukemia L1210 of IC50 10-100 μM.The most active were analogues 4c, 4d, 4e, and 6e (IC50 10-20 μM).The corresponding hydroxy derivatives were less active of inactive.Inhibition of macromolecular synthesis with compounds 4c, 4d, 6e, 9c, and 9d follows the order: DNA > RNA >/ protein.Cytotoxic effects of 4c, 6e, and 9d are not reversed with any of the four basic ribonucleosides or 2'-deoxyribonucleosides.Inhibitory activity of cytosine derivative 9c is reversed with uridine and 2'-deoxyuridine but not with the corresponding cytosine nucleosides.Zone assays in several tumor cell lines show that active compounds are cytotoxic agents with little selectivity for tumor cells.Analogue 6c showed 16.7percent ILS in leukemia P388/o implanted ip in mice at 510 and 1020 mg/kg, respectively.Cytallene (5b) and 6'β-hydroxyaristeromycin (10) exhibited significant activity against Friend and Rauscher murine leukemia viruses.The rest of the hydroxy derivatives, with the exception of 4a, were moderately effective or inactive as antiviral agents.None of the chloro derivatives or oxacyclopentenes exhibited an antiviral effect at noncytotoxic concentrations.Z-Olefin 4b and 2-aminoadenallene (5c) are substrates for adenosine deaminase.
Synthesis and antiherpetic activity of (±)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine and related compounds
Ashton,Canning Meurer,Cantone,Field,Hannah,Karkas,Liou,Patel,Perry,Wagner,Walton,Tolman
, p. 2304 - 2315 (2007/10/02)
A series of analogues of acyclovir and ganciclovir were prepared in which conformational constrainst were imposed by incorporation of a cyclopropane ring or unsaturation into the side chain. In addition, several related base-modified compounds were synthesized. These acyclonucleosides were evaluated for enzymatic phosphorylation and DNA polymerase inhibition in a staggered assay and for inhibitory activity against herpes simplex virus types 1 and 2 in vitro. Certain of the guanine or 8-azaguanine derivatives were good substrates for the viral thymidine kinase and were further converted to triphosphate, but none was a potent inhibitor of the viral DNA polymerase. Nevertheless, one member of this group, (±)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine (3a), displayed significant antiherpetic activity in vitro, superior to that of the corresponding cis olefin 4a. Another group, typified by (±)-9-[[(E)-2-(hydroxymethyl)cyclopropyl]methyl]adenine (17b), possessed modest antiviral activity despite an apparent inability to be enzymatically phosphorylated. The relationship of side-chain conformation and flexibility to biological activity in this series is discussed.
