99776-30-4Relevant 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.
GUANINE DERIVATIVE
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, (2008/06/13)
Antivirally active compounds of the formula STR1 wherein A is STR2 wherein m is 1 or 2, n is 1 or 2, whereby m is 1 when n is 2 and m is 2 when n is 1, R a ' is (CH 2) p OH, NHCONH 2 or COR a ", R a " is hydrogen, hydroxy or amino, p is 1 to 4, R b ' and R b " are independently selected from hydrogen or (CH 2) p OH, with the proviso that at least one of R b ' or R b " is hydrogen; or R b ' and R b " together constitute an additional carbon-carbon bond to form an alkyne; or a physiologically acceptable salt, geometric or optical isomer thereof; pharmaceutical preparations containing the compounds and methods for treatment of virus infections.
Nucleic Acid Derived Allenols: Unusual Analogues of Nucleosides with Antiretroviral Activity
Phadtare, Shashikant,Zemlicka, Jiri
, p. 5925 - 5931 (2007/10/02)
Racemic 1,2-butadien-4-ols substituted with a nucleic acid base were prepared by a base-catalyzed isomerization of the corresponding 2-butynols.With basic heterocycles such as adenine, cytosine, 5-methylcytosine, or N-guanine, the respective allenes were obtained without difficulty, but with guanine, side reactions were observed.Reaction of 2-butynols in stronger base (1 M NaOH) gave cyclized products-oxacyclopentenes 8a-c. (+/-)-Adenallene (3a) and (+/-)-cytallene (3c) are strong inhibitors of replication of human immunodeficiency virus(HIV) in vitro. (+/-)-Adenallene (3a) and butyne 6a are substrates for adenosine deaminase.Racemic 3a was deaminated quantitatively to (+/-)-hypoxallene (3h), indicating a low stereoselectivity as contrasted with the natural substrate-adenosine.When the deamination was stopped ad ca. 50percent conversion, (-)-adenallene (3a) and (+)-hypoxallene (3h) were obtained.Antiretroviral and adenosine deaminase substrate activities are discussed in terms of the similarity of several steric and stereoelectronic features of allenic derivatives of nucleic bases with those of the corresponding nucleosides or 2',3'-dideoxyribonuclesides.
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.
